A Review of Intervertebral Disc Degeneration Clinical Trial Protocols

A Review of Intervertebral Disc Degeneration Clinical Trial Protocols | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review A Review of Intervertebral Disc Degeneration Clinical Trial Protocols Francis Kiptengwer Chemorion, Marc-Antonio Bisotti This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5017042/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction Intervertebral disc degeneration (IVD) is a common condition causing chronic back pain and disability. Despite its global prevalence, the knowledge about treatment options that can be appraised is limited, and some current interventions often fail to provide enduring relief. This review explores IVD management strategies, including conservative, non-surgical, surgical, and regenerative approaches. Available clinical trial protocols were systematically analyzed to identify trends and knowledge gaps. Methods This paper conducted an examination of clinical trial protocols with the aim of showcasing the strategies employed by researchers to address intervertebral disc degeneration. Additionally, it enumerates both the primary and secondary outcomes, along with their respective measurement methods. This analysis seeks to identify gaps in existing knowledge and make valuable contributions to future research endeavors. To ensure a structured approach, the study adheres to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews (PRISMA). Results Out of the selected studies with protocols (N = 14) focusing on intervertebral disc degeneration, our analysis revealed that 3 (21%) were drug interventions, 3 (21%) were biological interventions, 7 (50%) were device interventions, and 1 (1%) was categorized as other. A chi-square goodness-of-fit test was employed to examine the distribution of these intervention types against an expected equal distribution. The statistical analysis yielded a chi-square statistic of 5.43, corresponding to a p-value of approximately 0.143. This indicates that, within the scope of our review, the distribution of intervention types does not significantly deviate from what might be expected by chance alone (p > 0.05), suggesting a relatively balanced exploration of intervention strategies in the existing literature. Discussion We observed that for the drug interventions, there was a shift toward multimodal pain management, especially after the opioid epidemic with alternatives such as liposome-encapsulated formulations; For medical devices, focus is on personalized and non-invasive technologies while in biological interventions, regenerative medicine is hugely stressed. There however is a huge divergence in the content and quality of Intervertebral disc degeneration clinical trial protocols, necessitating an investigation into the standardization of these protocols. This is because the content and quality of the protocol has a direct impact on the quality of data generated. Bioinformatics Intervertebral disc degeneration (IVD) chronic back pain clinical trial protocols interventions PRISMA guidelines Figures Figure 1 1 Introduction Intervertebral disc degeneration (IVD) is a prevalent condition that results in chronic back pain and disability. The degenerative process is marked by intricate biological and structural alterations in the intervertebral disc, potentially leading to disc herniation, spinal stenosis, and other spinal disorders (Adams & Roughley, 2006 ). It’s global prevalence has been reported to be as high as 58–84% in individuals aged 40–59, making it a leading cause for disability worldwide (Wu et al., 2020 ). Despite its widespread occurrence and significant impact on quality of life, the available treatment options for IVD are limited and often fail to provide enduring relief (Vos et al., 2012 ). The initial step in managing IVD is an accurate diagnosis, typically involving a comprehensive medical history, physical examination, and imaging studies such as MRI or CT scans. The diagnosis of IVD is often based on characteristic symptoms, such as back or neck pain and evidence of disc degeneration in imaging studies (Peng et al., 2021 ). Conservative treatment is commonly the first line of therapy for IVD, encompassing a variety of approaches such as physical therapy, pain management with medications, and lifestyle modifications. Physical therapy can aid in strengthening the muscles that support the spine, improving flexibility, and promoting good posture. Pain management can involve using non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and, in some cases, opioid medications (Xin et al., 2022 ). If conservative treatments prove ineffective, non-surgical treatments may be considered. Examples of these include epidural steroid injections, which can help to reduce inflammation and relieve pain and nerve blocking and radiofrequency ablation, which can help to disrupt the pain signals from the affected disc (Costăchescu et al., 2022 ). When conservative and non-surgical treatments have failed to provide relief or when the patient has severe or progressive neurological symptoms, surgical treatment is considered. Surgical options can include discectomy, where part or all of the degenerated disc is removed, and spinal fusion, where two or more vertebrae are fused to stabilize the spine (Ohnishi et al., 2022 ). Regenerative medicine also offers a promising direction for treatment, aiming to restore disc integrity through cell therapy and tissue engineering. Preclinical studies suggest that mesenchymal stem cells (MSCs) can differentiate into disc cells and produce vital matrix proteins, while advances in biomaterials provide scaffolds for cell delivery and disc repair (Chu et al., 2018 ). These approaches could shift IVD treatment from symptom relief to addressing root causes. In addition to those, alternative approaches such as acupuncture, chiropractic care, and massage therapy may be considered. While these treatments may not be as widely accepted or as well-studied as conventional treatments, some patients may find them helpful for managing their symptoms (Liu & Fu, 2022 ). Regardless of the treatment approach chosen, follow-up care and rehabilitation are crucial components of the treatment plan. This can include ongoing physical therapy, pain management, and lifestyle modifications to help prevent further disc degeneration and promote overall spinal health (Ashinsky et al., 2021 ). The adoption of these treatments relies on clinical trials confirming their safety and efficacy. To understand what researchers have devised to intervene in IVD, clinical trial platforms are a rich source of data that facilitate a standardized evaluation of existing clinical trials (Ashinsky et al., 2021 ). To key stakeholders, clinical trial protocols emerge as the foundational documents for capturing the comprehensive aspects of trials, such as design, methodology, and ethical considerations (Chan et al., 2013 ). 2 Methods 2.1 Study Design This study employed a systematic review approach to examine clinical trial protocols focused on intervertebral disc degeneration (IVD) interventions. The review process adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a structured and transparent methodology. 2.2 Research Question To guide our review, we formulated a research question using the PICOS (Population, Intervention, Comparison, Outcome, Study Design) framework: "In individuals with intervertebral disc degeneration (Population), what is the comprehensive overview of clinical trial protocols (Intervention) in comparison to conventional care or alternative interventions (Comparison), with a specific emphasis on essential outcomes (Outcome), as documented in the records accessible on the clinicaltrials.gov registry (Study Design)?" 2.3 Search Strategy We conducted a systematic search of the clinicaltrials.gov database, which was chosen for its comprehensive coverage of clinical trials globally. The search was performed using Medical Subject Headings (MeSH) terms and keywords related to intervertebral disc degeneration. The specific search string used was: ("Intervertebral Disc Degeneration" OR "Disc Degeneration") The search covered the period from 2013 to 2022, with no language restrictions applied. 2.4 Eligibility Criteria Inclusion criteria: Clinical trials focusing on intervertebral disc degeneration Trials with available protocols Interventional studies (drug, device, biological, or other interventions) Trials with results Exclusion criteria: Observational studies Trials without available protocols Trials without results Trials with recruitment status listed as "recruiting," "not yet recruiting," "enrolling by invitation," "suspended," "terminated," "withdrawn," or "unknown" 2.5 Study Selection Two independent researchers conducted the initial screening of records based on titles and basic information available on the clinicaltrials.gov platform. Full protocols were then assessed for eligibility. Disagreements were resolved through consensus. In cases where consensus could not be reached, a third reviewer was consulted. 2.6 Data Extraction Apart from the protocol, we also extracted the following data from each eligible study: Study title Intervention type (drug, device, biological, other) Primary outcome measures Secondary outcome measures Enrollment numbers Start date Completion date 2.7 Data Analysis Descriptive statistics were used to summarize the characteristics of included studies. We calculated frequencies and percentages for categorical variables (e.g., intervention types). A chi-square goodness-of-fit test was employed to examine the distribution of intervention types against an expected equal distribution. For the qualitative analysis, we employed a thematic approach to identify trends and patterns in the interventions, outcome measures, and overall trial designs. This involved a careful review of the extracted data, with particular attention to innovative approaches and emerging technologies in IVD management. 2.8 Quality Assessment While formal quality assessment tools are typically not applied to study protocols, we evaluated the completeness and clarity of the protocols based on the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This allowed us to comment on the overall quality and comprehensiveness of the available protocol information. 2.9 Ethical Consideration As this study was a review of publicly available clinical trial protocols, it did not require approval from an ethics committee. However, we adhered to ethical principles of research integrity throughout the review process, ensuring accurate representation of the data and appropriate attribution of sources. 3 Results The search revealed 477 Intervertebral Disc Degeneration (IVD) clinical trials. After an initial screening, in which trials that recruiting or not yet recruiting, ones that were actively not recruiting and terminated, enrolling by invitation and suspended, withdrawn and unknown studies were excluded, 194 studies were selected for closer review, and were further narrowed down to 128 studies after excluding observational studies. The other exclusion criteria that led to the removal of more studies at latter stages were 88 for lacking results, and 25 for not providing protocols. This selection process resulted in 15 trials that spanned from 2005 to 2022 with a median of 38 participants. Out of the selected studies with protocols, 3 (21%) were drug interventions, 3 (21%) were biological interventions, 7 (50%) were device interventions and 1 (1%) was categorized as other. Table 1 below shows the interventions that were devised presenting their titles, status, condition(s), interventions, sponsor, start and completion dates. Table 1 Characteristics of selected studies of IVD interventions NCT Number Study Title Study Status Conditions Interventions Sponsor Start Date Completion Date NCT03018392 Clinical and Radiological Evaluation of Patients With DDD Following TLIF With 3-D Printed Titanium Cage COMPLETED Intervertebral Disc Disease DEVICE: Stryker Tritanium Spinal System Bone and Joint Clinic of Baton Rouge 2017-01 1/28/2020 NCT03077204 BIO4 Clinical Case Study: Cervical Spine COMPLETED Degenerative Disc Disease|Trauma (Including Fractures)|Spondylolisthesis BIOLOGICAL: 1 or 2-Level ACDF utilizing BIO4 with Bio AVS Cervical Allograft (with graft window).|DEVICE: Aviator Anterior Cervical Plating System Seton Healthcare Family 4/6/2017 1/30/2020 NCT03484403 Benefit of Lumbar Bracing for Chronic Low Back Pain Due to Degenerative Disc Disease COMPLETED Degenerative Disc Disease|Lumbar Spondylosis|Low Back Pain OTHER: Lumbar back brace|BEHAVIORAL: Back school Dallas VA Medical Center ######### 9/30/2019 NCT03817606 A Comparison of Stryker's Tritanium Posterior Lumbar Cage and PEEK Implant TERMINATED Degenerative Disc Disease|Degenerative Scoliosis DEVICE: Tritanium Posterior Lumbar Cage|DEVICE: AVS UniLIF PEEK Posterior Lumbar Cage Riverside Medical Center 3/1/2019 4/27/2021 NCT02182843 Cellentra Viable Cell Bone Matrix (VCBM) Anterior Cervical Discectomy and Fusion Outcomes Study (VCBM/MaxAn) COMPLETED Cervical Disc Degenerative Disorder BIOLOGICAL: Cellentra VCBM Zimmer Biomet 2014-03 2018-01 NCT02070484 Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease TERMINATED Lumbar Degenerative Disc Disease|Spinal Stenosis|Spondylolisthesis|Spondylosis|Intervertebral Disk Displacement|Intervertebral Disk Degeneration|Spinal Diseases|Bone Diseases|Musculoskeletal Diseases|Spondylolysis BIOLOGICAL: NuCel|BIOLOGICAL: Demineralized Bone Matrix OhioHealth 2014-02 3/24/2017 NCT03647501 Lumbar Fusion With Nexxt Spine 3D-Printed Titanium Interbody Cages COMPLETED Lumbar Degenerative Disc Disease|Lumbar Spinal Stenosis|Lumbar Spondylolisthesis|Lumbar Spinal Deformity|Lumbar Spondylosis DEVICE: Interbody cage (titanium)|DEVICE: Interbody cage (PEEK) Ohio State University 8/22/2018 3/16/2022 NCT02539394 Effect of Topical Corticosteroids on Dysphagia in Anterior Cervical Discectomy and Fusion COMPLETED Cervical Disc Herniation|Cervical Degenerative Disc Disease|Cervical Spondylotic Myelopathy|Dysphagia|Osteoarthritis of Cervical Spine DRUG: Methylprednisolone Acetate|OTHER: Hemostatic Matrix Kit Hospital for Special Surgery, New York 2015-08 11/12/2021 NCT04007094 Single-Armed Use of ViviGen Cellular Bone Matrix in Patients Undergoing Posterolateral Lumbar Surgery TERMINATED Degenerative Disc Disease|Spinal Stenosis|Spondylosis|Spondylolisthesis OTHER: ViviGen Cellular Bone Matrix Ohio State University 2/12/2019 1/21/2022 NCT02347410 Spineology Clinical Outcomes Trial: An IDE Investigation COMPLETED Lumbar Degenerative Disc Disease DEVICE: SIFS graft containment device Spineology, Inc 1/22/2015 3/4/2020 NCT01829997 Assessment of nanOss Bioactive 3D in the Posterolateral Spine COMPLETED Degenerative Disc Disease|Spinal Stenosis|Spondylolisthesis DEVICE: nanOss Bioactive 3D BVF Pioneer Surgical Technology, Inc. 2013-04 2018-04 NCT02667067 Investigation of the Simplify® Cervical Artificial Disc COMPLETED Cervical Degenerative Disc Disease DEVICE: Simplify Disc|DEVICE: Anterior Cervical Discectomy & Fusion NuVasive 2015-11 7/29/2021 NCT02704689 AccuLIF® PROSPECTIVE PATIENT OUTCOMES STUDY TERMINATED Degenerative Disc Disease|Spondylolisthesis, Grade 1|Retrolisthesis DEVICE: AccuLIF expandable TLIF cage Stryker Spine 6/8/2016 1/19/2017 NCT03514277 A Prospective Study to Compare Bupivacaine and Exparel Versus Bupivacaine or Exparel Alone for Postoperative Pain Relief TERMINATED Low Back Pain|Lumbosacral Radiculopathy|Lumbar Disc Degeneration|Lumbar Disc Herniation|Stenosis|Spondylolisthesis|Spondylolysis|Deformity of Spine DRUG: Exparel|DRUG: Bupivacaine Virtua Health, Inc. 12/1/2016 12/31/2019 NCT02412735 Placebo-controlled Study to Evaluate Rexlemestrocel-L Alone or Combined With Hyaluronic Acid in Participants With Chronic Low Back Pain COMPLETED Degenerative Disc Disease DRUG: Rexlemestrocel-L|DRUG: Rexlemestrocel-L + HA Mixture|DRUG: Placebo Mesoblast, Ltd. 3/6/2015 6/15/2021 4 Discussion 4.1 Pharmacological Interventions 4.1.1 Bupivacaine Bupivacaine is a spinal anesthesia used in isobaric and hyperbaric forms (Moore, n.d.). It is administered intrathecally into the spine (Sng et al., 2016 ) bringing about a high frequency of satisfactory spinal nerve blockade and is widely used for all types of local anesthesia other than spinal anesthesia (Chambers, 1982 ). 4.1.2 Exparel Exparel represents a liposome-encapsulated bupivacaine product available in the market. It has received approval for use as a local anesthetic in treating wounds and for certain types of perineural injections, though its use is contraindicated for epidural or intrathecal injections(Eisenach & Yaksh, n.d.). The formulation is developed through DepoFoam technology, facilitating prolonged drug release. The shift towards its broader utilization was significantly influenced by the opioid crisis, prompting medical professionals to explore alternative multimodal strategies for managing pain after surgery (Kaye et al., 2020 ). 4.1.3 Methylprednisolone Acetate Methylprednisolone acetate is a corticosteroid particulate suspension injected into the spine as a common pain management procedure. The rationale for its use is the inhibition of inflammation implicated in axial pain and radiculopathy (MacMahon et al., 2016 ). Its dosage form contains excipients such as polythene glycol and miripirium (Schlatter et al., 2019 ). 4.1.4 Rexlemestrocel-L Rexlemestrocel-L is currently under investigation as a product derived from human bone marrow, categorized as an allogeneic mesenchymal precursor cell (MPC) therapy, aimed at addressing critical and life-threatening inflammatory diseases ( Rexlemestrocel-L , n.d.). Administering a single dose of Rexlemestrocel-L combined with hyaluronic acid (HA) into the lumbar disc is observed to notably decrease pain levels. This therapeutic approach utilizes advanced mesenchymal lineage cell therapy technology to tackle severe inflammation. It achieves this by secreting anti-inflammatory agents that effectively interact with and adjust various components of the immune system, thereby substantially mitigating the impact of inflammatory processes that contribute to pain ( FDA Grants Regenerative Medicine Advanced Therapy (Rmat) Designation for Rexlemestrocel-L in Chronic Low Back Pain , n.d.). 4.2 Medical Devices 4.2.1 AVS UniLIF PEEK Posterior Lumbar Cage AVS UniLIF is a posterior lumbar PEEK spacer crafted for use in both bilateral PLIF and oblique TLIF surgical techniques. Its design includes standard lengths suitable for bilateral PLIF procedures and extended lengths featuring obliquely angled lordotic profiles for unilateral TLIF methods. This design permits the insertion of a single spacer diagonally through the disc space to effectively achieve lordosis correction within the desired anterior-posterior dimension. The product offers a wide range of sizes in terms of length, height, and lordotic angles to accommodate diverse patient anatomical requirements. It features a spacious internal chamber designated for bone graft material, incorporates serrations on its upper and lower surfaces to support multi-directional fixation, and is designed with ergonomically contoured anterior edges alongside flat posterior edges to enhance its application ( AVS UniLIF , n.d.). 4.2.2 Simplify Disc The Simplify® Cervical Artificial Disc, created by Nuvasive, Inc. based in San Diego, CA, is designed with PEEK (polyetheretherketone) endplates and a mobile core made from zirconia-toughened alumina ceramic. The endplates are coated with commercially pure titanium and are designed with concave articulating surfaces, while the ceramic core features two convex surfaces. This device is distinguished by its adaptability, offering endplates in small, medium, and large sizes, three variations in thickness that correspond to device heights of 4, 5, and 6 mm, and lordosis angles of 0° and 5°. A significant design element is the inclusion of a retention ring on the superior endplate to ensure core stability. Its versatility allows for accommodation of varying anatomical needs, positioning it as a significant advancement in the field of cervical artificial disc technology (Guyer et al., 2021 ). 4.2.3 nanOss Bioactive 3D BVF The nanOss Bioactive 3D BVF is designed as a bone void filler that combines osteoconductive nano-structured hydroxyapatite (HA) with a specially engineered extracellular matrix bioscaffold to promote the natural formation of bone. In this innovative composition, nano-structured HA particles are integrated into a porous, gelatin-based foam. This product acts as a resorbable, porous calcium phosphate filler, creating a scaffold that encourages the growth of new bone tissue. It features an interconnected porosity that mimics the structure of human cancellous bone, making it an effective osteoconductive implant. The semi-rigid, three-dimensional structure contains porous hydroxyapatite granules embedded in a gelatin-based foam matrix derived from highly purified porcine collagen. Available in strip form, it allows for customization during surgical procedures. When hydrated at the site of implantation, nanOss Bioactive 3D becomes a compressible, elastic sponge, conforming to the shape of the bone defect to ensure optimal contact with the surrounding healthy bone. This product is sterilized using gamma irradiation and is intended for single-use only ( nanOss_Bioactive_OUS_System_Overview , n.d.). 4.2.4 Stryker Tritanium Spinal System The Tritanium PL Posterior Lumbar Cage represents a distinctive advancement in spinal implant technology. Crafted using AMagine Technology, our proprietary additive manufacturing approach, this hollow, rectangular implant boasts a unique configuration that combines solid and porous structures. Designed to cater to diverse patient anatomies, the Tritanium PL Cage is available in various widths, lengths, heights, and lordotic angles. Notable features include a spacious graft window and a sleek wedge nose, streamlining the insertion process into the disc space. With a threaded inserter connection, the implant ensures both rigid connectivity and precise control during insertion. Additionally, a circular dimple serves as an indicator for the correct insertion orientation, facilitating accurate positioning of the lordotic cages. This innovation in spinal cage design showcases a commitment to versatility, precision, and patient-specific adaptability ( Tritanium PL , n.d.). 4.2.5 AccuLIF expandable TLIF cage The AccuLIF lumbar interbody technology by Stryker Spine, part of the LITe (Less Invasive Technologies). This rectangular implant, utilizing a combination of solid and porous structures, allows for insertion at a smaller starting height and subsequent expansion based on patient anatomy, ensuring an optimal endplate-to-endplate fit. With features such as a large graft window and a surgeon-controlled hydraulic expansion mechanism operating in 1mm increments, the device emphasizes adaptability and precision in lumbar spinal interventions. Designed to preserve endplate integrity, minimize impaction forces, and protect neural elements, AccuLIF underscores a commitment to patient-centric outcomes in spinal surgery ( AccuLIF® , n.d.). 4.2.6 SIFS graft containment device The Spineology Interbody Fusion System (SIFS) is an innovative lumbar intervertebral body fusion device designed to aid in the treatment of degenerative disc disease (DDD) and Grade 1 spondylolisthesis in skeletally mature patients. Manufactured by Spineology, Inc., the SIFS implant features a PET mesh bag that facilitates the containment of compatible allograft and autograft materials. This device is indicated for use as an adjunct to fusion in the lumbar spine, offering versatility with various widths, lengths, and heights. The system, when used in conjunction with posterior supplemental fixation, provides a comprehensive solution for fusion procedures. The SIFS implant, with its non-ferromagnetic and PET composition, ensures compatibility with various clinical settings. The device's unique design, combining efficiency and adaptability, underscores its role in advancing lumbar spinal interventions ( Spineology Interbody Fusion System , n.d.). 4.2.7 Nexxt Spine 3D-Printed Titanium Interbody Cages The Nexxt Spine 3D-Printed Titanium Interbody Cages are innovative components within the NEXXT MATRIXX® SYSTEM. These cages, crafted from titanium using advanced 3D-printing technology, offer structural integrity and radiolucency. Designed for lumbar fusion procedures, they are compatible with supplemental fixation systems such as the Nexxt Spine Inertia® Pedicle Screw System, Inertia® MIS Pedicle Screw System, or Facet Fixx® Screw System. Patient positioning involves the prone position on a radiolucent spine table, and the surgical steps include discectomy, distraction, decompression, endplate preparation, and precise implant insertion. The 3D-printed titanium construction emphasizes durability and biocompatibility, contributing to successful fusion outcomes with minimal complications ( NEXXT MATRIXX® TLIF / TLIF Oblique Interbodies , n.d.). 4.2.8 HonourTM poly-ether-ether-ketone cage The HONOUR® Spacer System for TLIF and tPLIF is a radiolucent cage constructed from medical-grade polyetheretherketone with tantalum markers, complying with ASTM F-2026 and ASTM F-560 standards. Patient positioning involves placing the patient in the prone position on a radiolucent spine table, minimizing ocular and nerve compression risks. Operative exposure is facilitated by fluoroscopic imaging and palpation, with HONOUR® TLIF/tPLIF Interbodies indicated for up to two contiguous levels in the lumbar spine. The surgical procedure includes disc space distraction, decompression, and endplate preparation. The lumbar straight and curved devices are chosen based on trial spacer fitting, ensuring disc height restoration. Implant placement involves autogenous bone graft material, attachment to the threaded inserter, and careful insertion, guided by fluoroscopic imaging. Bilateral approaches require attention to contralateral implant placement. Implant removal is achieved using the threaded implant inserter or a removal hook if needed ( HONOUR ® tPLIF / TLIF Interbodies , n.d.). 4.2.9 Aviator Anterior Cervical Plating System The Aviator Anterior Cervical Plating System is distinguished by its innovative double screw locking mechanism, which allows for extensive screw angulation and features streamlined instrumentation. Its primary locking mechanism utilizes a spring-loaded bar that automatically snaps into place over the screws, ensuring they are locked with both visual and tactile indicators. The system incorporates both fixed and variable angle screws, supporting a wide range of bone screw fixation techniques. Made from Titanium Alloy, the plate is 2.5mm in thickness and 17.4mm in width, and it is designed with a lordotic curve, windows for graft viewing, and screws that are self-tapping and self-drilling, available in diameters of 4.0mm and 4.35mm, with color coding for straightforward identification. Proper patient positioning and precise incision placement are vital, followed by a detailed discectomy or corpectomy, and careful removal of any obstructive bony structures. The Aviator System is crafted to offer surgeons a flexible and effective approach to anterior cervical plating, adapting seamlessly to a variety of surgical methods and patient anatomical requirements ( Aviator® Anterior Cervical Plating System , n.d.). 4.3 Biological and Other interventions 4.3.1 Cellentra VCBM Biomet Inc.'s Cellentra VCBM represents a state-of-the-art bone growth enhancer utilizing AlloStem Stem Cell technology, derived from the adipose tissue of adult humans. This allograft undergoes a rigorous processing protocol to preserve its regenerative capabilities, aiming to promote bone formation and accelerate the healing process. Adipose tissue is recognized for its abundance of stem cells, which some research highlights as a key stem cell reservoir in the body. Cellentra VCBM sets itself apart by offering a potent mix of factors conducive to bone healing, including an osteoconductive framework that supports the growth of osteogenic cells and mesenchymal stem cells (MSCs), both known for their osteoinductive potential. The graft is enriched with critical growth factors such as bone morphogenetic proteins (BMP-2, -4, -7), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1), and fibroblast growth factor (FGF). With a cancellous bone matrix featuring a trabecular structure that is interconnected, Cellentra VCBM optimizes osteoconductivity, thereby facilitating enhanced bone regeneration (Wei et al., 2014 ). 4.3.2 NuCel NuCel® is a cryogenically preserved amniotic suspension allograft, obtained from the human amniotic membrane (AM) and cells within the amniotic fluid, specifically processed to preserve its biological activity. When used in conjunction with a bone allograft for lumbar interbody fusion surgeries, the integration of NuCel® has been shown to achieve a clinical fusion rate that rivals that of traditional lumbar interbody fusion techniques (Etchebarne et al., 2021 ). 4.3.3 Demineralized Bone Matrix Demineralized bone matrix (DBM) is a well-established biomaterial and medically approved device for addressing bone defects, boasting an extensive history of application across various clinical settings. Sourced from human bone, DBM preserves the bone's inherent protein content, along with minimal quantities of calcium compounds, inorganic phosphates, and residual cellular material. It is offered in multiple formats, including putty, paste, sheets, and malleable pieces, acting as a biodegradable scaffold that promotes the release of powerful osteogenic substances such as growth factors. DBM is recognized for its osteoconductive and osteoinductive capabilities, fostering new bone growth, expediting the healing process, and opening avenues for advancements in orthopedic restoration and regenerative medicine (Gruskin et al., 2012 ). 4.3.4 BIO4 Bone Matrix The BIO4 Bone Matrix is a cryogenically preserved viable bone matrix that encompasses the natural matrix, endogenous osteoblasts, mesenchymal stem cells (MSCs), as well as osteoinductive and angiogenic growth factors (Lin et al., 2020). This product is tailored for patients undergoing Anterior Cervical Discectomy and Fusion (ACDF) procedures. Its development targets the fulfillment of the four essential properties necessary for effective bone healing and regeneration: osteoconductivity, osteoinductivity, osteogenicity, and angiogenicity. BIO4 serves as an alternative to autografts, aiming to minimize the risk of complications that can arise from graft harvesting ( Research Proposal , 2014). 4.4 Conclusion The examination of intervertebral disc degeneration (IVD) trial protocols has offered a comprehensive insight into contemporary trends in spinal interventions, shaping a dynamic landscape dedicated to optimizing patient outcomes. This synthesis explores key findings in pharmacological interventions (drugs), medical devices, and biological interventions, drawing upon pertinent research in the field of spinal healthcare. A notable trend is the significant shift towards multimodal pain management, acknowledging and addressing the opioid epidemic. Alternatives like bupivacaine and Exparel have gained prominence, underscoring efforts to minimize opioid dependence while ensuring efficacious analgesia. The integration of innovative drug delivery systems, exemplified by liposome-encapsulated formulations like Exparel, highlights a commitment to precision and sustained therapeutic efficacy. Additionally, the investigational use of Rexlemestrocel-L, a mesenchymal precursor cell product, signifies a transformative phase by not only alleviating symptoms but actively contributing to tissue repair and regeneration. The medical devices in spinal interventions demonstrate a commitment to precision and personalized treatment strategies. Noteworthy examples include the AVS UniLIF posterior lumbar cage and the Simplify Disc cervical artificial disc, showcasing the trend towards tailoring devices to individual anatomies for optimal outcomes in spinal surgery. The incorporation of 3D-printed titanium in devices like the Tritanium PL Posterior Lumbar Cage represents a convergence of materials science and surgical innovation, enhancing structural integrity and bio integration potential. Minimally invasive technologies, such as the AccuLIF expandable TLIF cage, underscore a commitment to patient safety and reduced surgical invasiveness. The realm of biological interventions unfolds with promising advancements such as Cellentra VCBM, a bone growth substitute leveraging AlloStem Stem Cell technology. This innovative approach stimulates bone growth and facilitates healing by incorporating essential growth factors within an osteoconductive scaffold. NuCel, an amniotic suspension allograft, demonstrates high clinical fusion rates in lumbar interbody fusion, highlighting its efficacy comparable to conventional procedures. The use of cryopreserved viable bone matrix, as seen in BIO4 Bone Matrix, showcases a holistic approach fulfilling crucial characteristics for bone repair and regeneration in spine surgery. 4.5 Implications for Research The divergence observed in current intervertebral disc degeneration (IVD) trial protocols underscores the critical need for standardization. The identified variations, ranging from inclusion criteria to outcome measures, emphasize the importance of establishing consensus on key elements. Standardized protocols not only enhance the comparability of study outcomes but also facilitate meta-analyses, systematic reviews, and cumulative knowledge generation. A crucial implication is the encouragement of an open-access culture in sharing clinical trial protocols, promoting transparency and collaboration. By fostering a shared understanding of interventions and methodological nuances, this approach not only expedites individual studies but also contributes to the collective advancement of spinal healthcare research. The call for standardization and open-access protocols reflects a commitment to elevating the rigor, reproducibility, and impact of future investigations in the field. Declarations Conflict of Interest: none declared. Funding This project was supported by the Marie Skłodowska-Curie International Training Network “Disc4All” under grant agreement #955735. References AccuLIF® . (n.d.). https://thespinemarketgroup.com/wp-content/uploads/2020/07/Acculif.SGT-Stryker.pdf Adams MA, Roughley PJ (2006) What is intervertebral disc degeneration, and what causes it? Spine 31(18):2151–2161. https://doi.org/10.1097/01.brs.0000231761.73859.2c Ashinsky B, Smith HE, Mauck RL, Gullbrand SE (2021) Intervertebral disc degeneration and regeneration: A motion segment perspective. Eur Cells Mater 41:370–380. https://doi.org/10.22203/eCM.v041a24 Aviator® Anterior Cervical Plating System . (n.d.). https://thespinemarketgroup.com/wp-content/uploads/2021/12/Aviator-Cervical-Plate-SGT.Stryker.pdf AVS UniLIF. (n.d.). Retrieved January 17 (2024) from https://www.stryker.com/us/en/spine/products/avs-unilif.html Chambers WA (1982) INTRATHECAL BUPIVACAINE. Br J Anaesth 54(8):799–801. https://doi.org/10.1093/bja/54.8.799 Chan A-W, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleža-Jerić K, Laupacis A, Moher D (2013) SPIRIT 2013 explanation and elaboration: Guidance for protocols of clinical trials. BMJ 346:e7586. https://doi.org/10.1136/bmj.e7586 Chu G, Shi C, Wang H, Zhang W, Yang H, Li B (2018) Strategies for Annulus Fibrosus Regeneration: From Biological Therapies to Tissue Engineering. Front Bioeng Biotechnol 6:90. https://doi.org/10.3389/fbioe.2018.00090 Costăchescu B, Niculescu A-G, Teleanu RI, Iliescu BF, Rădulescu M, Grumezescu AM, Dabija MG (2022) Recent Advances in Managing Spinal Intervertebral Discs Degeneration. Int J Mol Sci 23(12):6460. https://doi.org/10.3390/ijms23126460 Eisenach JC, Yaksh TL (n.d.). Spinal Exparel®dan extended duration of preclinical study needed Etchebarne M, Fricain J-C, Kerdjoudj H, Di Pietro R, Wolbank S, Gindraux F, Fenelon M (2021) Use of Amniotic Membrane and Its Derived Products for Bone Regeneration: A Systematic Review. Front Bioeng Biotechnol 9:661332. https://doi.org/10.3389/fbioe.2021.661332 FDA Grants Regenerative Medicine Advanced Therapy (Rmat) Designation for Rexlemestrocel-L in Chronic Low Back Pain . (n.d.). BioSpace. Retrieved January 17, (2024) from https://www.biospace.com/article/fda-grants-regenerative-medicine-advanced-therapy-rmat-designation-for-rexlemestrocel-l-in-chronic-low-back-pain-/ Gruskin E, Doll BA, Futrell FW, Schmitz JP, Hollinger JO (2012) Demineralized bone matrix in bone repair: History and use. Adv Drug Deliv Rev 64(12):1063–1077. https://doi.org/10.1016/j.addr.2012.06.008 Guyer RD, Coric D, Nunley PD, Sasso RC, Musacchio M, Bae HW, Peloza JH, Ohnmeiss DD (2021) Single-Level Cervical Disc Replacement Using a PEEK-on-Ceramic Implant: Results of a Multicenter FDA IDE Trial With 24-Month Follow-up. Int J Spine Surg 15(4):633–644. https://doi.org/10.14444/8084 HONOUR ® tPLIF / TLIF Interbodies . (n.d.). https://nexxtspine.showpad.com/share/8xE9u20GtcxeBmRjFnHXu Kaye AD, Armstead-Williams C, Hyatali F, Cox KS, Kaye RJ, Eng LK, Anwar F, Patel MA, Patil PV, S., Cornett EM (2020) Exparel for Postoperative Pain Management: A Comprehensive Review. Curr Pain Headache Rep 24(11):73. https://doi.org/10.1007/s11916-020-00905-4 Liu Z, Fu C (2022) Application of single and cooperative different delivery systems for the treatment of intervertebral disc degeneration. Frontiers in Bioengineering and Biotechnology , 10 . https://www.frontiersin.org/articles/ 10.3389/fbioe.2022.1058251 MacMahon PJ, Huang AJ, Palmer WE (2016) Spine Injectables: What Is the Safest Cocktail? Am J Roentgenol 207(3):526–533. https://doi.org/10.2214/AJR.16.16379 Moore DC (n.d.). Spinal Anesthesia: Bupivacaine Compared with Tet racaine. ANESTHESIA AND ANALGESIA nanOss_Bioactive_OUS_System_Overview . (n.d.). https://www.lifehealthcare.com.au/wp-content/uploads/2017/06/nanOss_Bioactive_OUS_System_Overview.pdf NEXXT, MATRIXX® TLIF / TLIF Oblique Interbodies . (n.d.). https://thespinemarketgroup.com/wp-content/uploads/2020/08/Matrixx-Lumbar-STG-Nexxt-Spine.pdf Ohnishi T, Iwasaki N, Sudo H (2022) Causes of and Molecular Targets for the Treatment of Intervertebral Disc Degeneration: A Review. Cells 11(3):394. https://doi.org/10.3390/cells11030394 Peng Y, Qing X, Shu H, Tian S, Yang W, Chen S, Lin H, Lv X, Zhao L, Chen X, Pu F, Huang D, Cao X, Shao Z (2021) Proper animal experimental designs for preclinical research of biomaterials for intervertebral disc regeneration. Biomaterials Translational 2(2):91–142. https://doi.org/10.12336/biomatertransl.2021.02.003 Research Proposal . (2014) Rexlemestrocel (ed) (n.d.). Retrieved January 17, 2024, from https://go.drugbank.com/drugs/DB17606 Schlatter J, Nguyen D, Zamy M, Kabiche S, Fontan J-E, Cisternino S (2019) Safety of intrathecal route: Focus to methylprednisolone acetate (Depo-Medrol) use. Eur Spine J 28(1):21–30. https://doi.org/10.1007/s00586-017-5387-x Sng BL, Siddiqui FJ, Leong WL, Assam PN, Chan ES, Tan KH, Sia AT (2016) Hyperbaric versus isobaric bupivacaine for spinal anaesthesia for caesarean section. Cochrane Database of Systematic Reviews , 2016 (9). https://doi.org/10.1002/14651858.cd005143.pub3 Spineology Interbody Fusion System . (n.d.). https://www.accessdata.fda.gov/cdrh_docs/pdf20/DEN200010.pdf Tritanium PL. (n.d.). Retrieved January 17 (2024) from https://www.stryker.com/us/en/spine/products/tritanium-pl.html Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham jerry, Ackerman I, Aggarwal R, Ahn SY, Ali MK, AlMazroa MA, Alvarado M, Anderson HR, Anderson LM, Murray CJL (2012) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet (London England) 380(9859):2163–2196. https://doi.org/10.1016/S0140-6736(12)61729-2 Wei C-C, Lin AB, Hung S-C (2014) Mesenchymal Stem Cells in Regenerative Medicine for Musculoskeletal Diseases: Bench, Bedside, and Industry. Cell Transplant 23(4–5):505–512. https://doi.org/10.3727/096368914X678328 Wu A, March L, Zheng X, Huang J, Wang X, Zhao J, Blyth FM, Smith E, Buchbinder R, Hoy D (2020) Global low back pain prevalence and years lived with disability from 1990 to 2017: Estimates from the Global Burden of Disease Study 2017. Annals Translational Med 8(6):299–299. https://doi.org/10.21037/atm.2020.02.175 Xin J, Wang Y, Zheng Z, Wang S, Na S, Zhang S (2022) Treatment of Intervertebral Disc Degeneration. Orthop Surg 14(7):1271–1280. https://doi.org/10.1111/os.13254 Additional Declarations The authors declare no competing interests. Supplementary Files ctgstudies.csv Selected Studies Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5017042","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":348294221,"identity":"4fa052ac-e1e2-4636-9c20-47797beff21c","order_by":0,"name":"Francis Kiptengwer Chemorion","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-2099-0035","institution":"University of Pompeu Fabra","correspondingAuthor":true,"prefix":"","firstName":"Francis","middleName":"Kiptengwer","lastName":"Chemorion","suffix":""},{"id":348294220,"identity":"98052326-8efd-4510-a3a0-8c64f7d51095","order_by":1,"name":"Marc-Antonio Bisotti","email":"","orcid":"","institution":"Insilicotrials Technologies","correspondingAuthor":false,"prefix":"","firstName":"Marc-Antonio","middleName":"","lastName":"Bisotti","suffix":""}],"badges":[],"createdAt":"2024-09-02 09:24:24","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":true,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":true},"doi":"10.21203/rs.3.rs-5017042/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5017042/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":64004301,"identity":"8533b2fa-6f78-460b-918a-9bae03e7c201","added_by":"auto","created_at":"2024-09-04 21:21:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":42382,"visible":true,"origin":"","legend":"\u003cp\u003eSelection of IVD Clinical Trial Protocols\u003c/p\u003e","description":"","filename":"prismaflowchart.png","url":"https://assets-eu.researchsquare.com/files/rs-5017042/v1/ec01b0913113a65270a1a144.png"},{"id":64004303,"identity":"49d0628e-99a4-4eb9-a723-eb08fc7a8777","added_by":"auto","created_at":"2024-09-04 21:21:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":630291,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5017042/v1/72628b41-a498-4bf2-a6a5-dc17fb9f9e0e.pdf"},{"id":64004302,"identity":"95b3c249-8566-4224-a5bf-290a0988ce9a","added_by":"auto","created_at":"2024-09-04 21:21:01","extension":"csv","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":6139,"visible":true,"origin":"","legend":"\u003cp\u003eSelected Studies\u003c/p\u003e","description":"","filename":"ctgstudies.csv","url":"https://assets-eu.researchsquare.com/files/rs-5017042/v1/40f95d5e5b3a1309dd657f0c.csv"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eA Review of Intervertebral Disc Degeneration Clinical Trial Protocols\u003c/p\u003e","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eIntervertebral disc degeneration (IVD) is a prevalent condition that results in chronic back pain and disability. The degenerative process is marked by intricate biological and structural alterations in the intervertebral disc, potentially leading to disc herniation, spinal stenosis, and other spinal disorders (Adams \u0026amp; Roughley, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). It\u0026rsquo;s global prevalence has been reported to be as high as 58\u0026ndash;84% in individuals aged 40\u0026ndash;59, making it a leading cause for disability worldwide (Wu et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Despite its widespread occurrence and significant impact on quality of life, the available treatment options for IVD are limited and often fail to provide enduring relief (Vos et al., \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2012\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe initial step in managing IVD is an accurate diagnosis, typically involving a comprehensive medical history, physical examination, and imaging studies such as MRI or CT scans. The diagnosis of IVD is often based on characteristic symptoms, such as back or neck pain and evidence of disc degeneration in imaging studies (Peng et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eConservative treatment is commonly the first line of therapy for IVD, encompassing a variety of approaches such as physical therapy, pain management with medications, and lifestyle modifications. Physical therapy can aid in strengthening the muscles that support the spine, improving flexibility, and promoting good posture. Pain management can involve using non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and, in some cases, opioid medications (Xin et al., \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIf conservative treatments prove ineffective, non-surgical treatments may be considered. Examples of these include epidural steroid injections, which can help to reduce inflammation and relieve pain and nerve blocking and radiofrequency ablation, which can help to disrupt the pain signals from the affected disc (Costăchescu et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhen conservative and non-surgical treatments have failed to provide relief or when the patient has severe or progressive neurological symptoms, surgical treatment is considered. Surgical options can include discectomy, where part or all of the degenerated disc is removed, and spinal fusion, where two or more vertebrae are fused to stabilize the spine (Ohnishi et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRegenerative medicine also offers a promising direction for treatment, aiming to restore disc integrity through cell therapy and tissue engineering. Preclinical studies suggest that mesenchymal stem cells (MSCs) can differentiate into disc cells and produce vital matrix proteins, while advances in biomaterials provide scaffolds for cell delivery and disc repair (Chu et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). These approaches could shift IVD treatment from symptom relief to addressing root causes.\u003c/p\u003e \u003cp\u003eIn addition to those, alternative approaches such as acupuncture, chiropractic care, and massage therapy may be considered. While these treatments may not be as widely accepted or as well-studied as conventional treatments, some patients may find them helpful for managing their symptoms (Liu \u0026amp; Fu, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Regardless of the treatment approach chosen, follow-up care and rehabilitation are crucial components of the treatment plan. This can include ongoing physical therapy, pain management, and lifestyle modifications to help prevent further disc degeneration and promote overall spinal health (Ashinsky et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe adoption of these treatments relies on clinical trials confirming their safety and efficacy. To understand what researchers have devised to intervene in IVD, clinical trial platforms are a rich source of data that facilitate a standardized evaluation of existing clinical trials (Ashinsky et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). To key stakeholders, clinical trial protocols emerge as the foundational documents for capturing the comprehensive aspects of trials, such as design, methodology, and ethical considerations (Chan et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2013\u003c/span\u003e).\u003c/p\u003e"},{"header":"2 Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003e2.1 Study Design\u003c/h2\u003e\n\u003cp\u003eThis study employed a systematic review approach to examine clinical trial protocols focused on intervertebral disc degeneration (IVD) interventions. The review process adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a structured and transparent methodology.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003e2.2 Research Question\u003c/h2\u003e\n\u003cp\u003eTo guide our review, we formulated a research question using the PICOS (Population, Intervention, Comparison, Outcome, Study Design) framework:\u003c/p\u003e\n\u003cp\u003e\"In individuals with intervertebral disc degeneration (Population), what is the comprehensive overview of clinical trial protocols (Intervention) in comparison to conventional care or alternative interventions (Comparison), with a specific emphasis on essential outcomes (Outcome), as documented in the records accessible on the clinicaltrials.gov registry (Study Design)?\"\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003e2.3 Search Strategy\u003c/h2\u003e\n\u003cp\u003eWe conducted a systematic search of the clinicaltrials.gov database, which was chosen for its comprehensive coverage of clinical trials globally. The search was performed using Medical Subject Headings (MeSH) terms and keywords related to intervertebral disc degeneration. The specific search string used was:\u003c/p\u003e\n\u003cp\u003e(\"Intervertebral Disc Degeneration\" OR \"Disc Degeneration\")\u003c/p\u003e\n\u003cp\u003eThe search covered the period from 2013 to 2022, with no language restrictions applied.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003e2.4 Eligibility Criteria\u003c/h2\u003e\n\u003cp\u003eInclusion criteria:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eClinical trials focusing on intervertebral disc degeneration\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eTrials with available protocols\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eInterventional studies (drug, device, biological, or other interventions)\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eTrials with results\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eExclusion criteria:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eObservational studies\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eTrials without available protocols\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eTrials without results\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eTrials with recruitment status listed as \"recruiting,\" \"not yet recruiting,\" \"enrolling by invitation,\" \"suspended,\" \"terminated,\" \"withdrawn,\" or \"unknown\"\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch2\u003e2.5 Study Selection\u003c/h2\u003e\n\u003cp\u003eTwo independent researchers conducted the initial screening of records based on titles and basic information available on the clinicaltrials.gov platform. Full protocols were then assessed for eligibility. Disagreements were resolved through consensus. In cases where consensus could not be reached, a third reviewer was consulted.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003ch2\u003e2.6 Data Extraction\u003c/h2\u003e\n\u003cp\u003eApart from the protocol, we also extracted the following data from each eligible study:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eStudy title\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eIntervention type (drug, device, biological, other)\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003ePrimary outcome measures\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eSecondary outcome measures\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eEnrollment numbers\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eStart date\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eCompletion date\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003e2.7 Data Analysis\u003c/h2\u003e\n\u003cp\u003eDescriptive statistics were used to summarize the characteristics of included studies. We calculated frequencies and percentages for categorical variables (e.g., intervention types). A chi-square goodness-of-fit test was employed to examine the distribution of intervention types against an expected equal distribution.\u003c/p\u003e\n\u003cp\u003eFor the qualitative analysis, we employed a thematic approach to identify trends and patterns in the interventions, outcome measures, and overall trial designs. This involved a careful review of the extracted data, with particular attention to innovative approaches and emerging technologies in IVD management.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n\u003ch2\u003e2.8 Quality Assessment\u003c/h2\u003e\n\u003cp\u003eWhile formal quality assessment tools are typically not applied to study protocols, we evaluated the completeness and clarity of the protocols based on the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This allowed us to comment on the overall quality and comprehensiveness of the available protocol information.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003e2.9 Ethical Consideration\u003c/h2\u003e\n\u003cp\u003eAs this study was a review of publicly available clinical trial protocols, it did not require approval from an ethics committee. However, we adhered to ethical principles of research integrity throughout the review process, ensuring accurate representation of the data and appropriate attribution of sources.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"3 Results","content":"\u003cp\u003eThe search revealed 477 Intervertebral Disc Degeneration (IVD) clinical trials. After an initial screening, in which trials that recruiting or not yet recruiting, ones that were actively not recruiting and terminated, enrolling by invitation and suspended, withdrawn and unknown studies were excluded, 194 studies were selected for closer review, and were further narrowed down to 128 studies after excluding observational studies. The other exclusion criteria that led to the removal of more studies at latter stages were 88 for lacking results, and 25 for not providing protocols. This selection process resulted in 15 trials that spanned from 2005 to 2022 with a median of 38 participants.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOut of the selected studies with protocols, 3 (21%) were drug interventions, 3 (21%) were biological interventions, 7 (50%) were device interventions and 1 (1%) was categorized as other. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e below shows the interventions that were devised presenting their titles, status, condition(s), interventions, sponsor, start and completion dates.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of selected studies of IVD interventions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT Number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudy Title\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy Status\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eConditions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInterventions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSponsor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eStart Date\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCompletion Date\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT03018392\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eClinical and Radiological Evaluation of Patients With DDD Following TLIF With 3-D Printed Titanium Cage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOMPLETED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIntervertebral Disc Disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDEVICE: Stryker Tritanium Spinal System\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBone and Joint Clinic of Baton Rouge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2017-01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1/28/2020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT03077204\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBIO4 Clinical Case Study: Cervical Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOMPLETED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDegenerative Disc Disease|Trauma (Including Fractures)|Spondylolisthesis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBIOLOGICAL: 1 or 2-Level ACDF utilizing BIO4 with Bio AVS Cervical Allograft (with graft window).|DEVICE: Aviator Anterior Cervical Plating System\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSeton Healthcare Family\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4/6/2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1/30/2020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT03484403\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBenefit of Lumbar Bracing for Chronic Low Back Pain Due to Degenerative Disc Disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOMPLETED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDegenerative Disc Disease|Lumbar Spondylosis|Low Back Pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOTHER: Lumbar back brace|BEHAVIORAL: Back school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDallas VA Medical Center\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e#########\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9/30/2019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT03817606\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA Comparison of Stryker's Tritanium Posterior Lumbar Cage and PEEK Implant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTERMINATED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDegenerative Disc Disease|Degenerative Scoliosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDEVICE: Tritanium Posterior Lumbar Cage|DEVICE: AVS UniLIF PEEK Posterior Lumbar Cage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRiverside Medical Center\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3/1/2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4/27/2021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT02182843\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCellentra Viable Cell Bone Matrix (VCBM) Anterior Cervical Discectomy and Fusion Outcomes Study (VCBM/MaxAn)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOMPLETED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCervical Disc Degenerative Disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBIOLOGICAL: Cellentra VCBM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eZimmer Biomet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2014-03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2018-01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT02070484\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHuman Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTERMINATED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLumbar Degenerative Disc Disease|Spinal Stenosis|Spondylolisthesis|Spondylosis|Intervertebral Disk Displacement|Intervertebral Disk Degeneration|Spinal Diseases|Bone Diseases|Musculoskeletal Diseases|Spondylolysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBIOLOGICAL: NuCel|BIOLOGICAL: Demineralized Bone Matrix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOhioHealth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2014-02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3/24/2017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT03647501\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLumbar Fusion With Nexxt Spine 3D-Printed Titanium Interbody Cages\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOMPLETED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLumbar Degenerative Disc Disease|Lumbar Spinal Stenosis|Lumbar Spondylolisthesis|Lumbar Spinal Deformity|Lumbar Spondylosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDEVICE: Interbody cage (titanium)|DEVICE: Interbody cage (PEEK)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOhio State University\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8/22/2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3/16/2022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT02539394\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEffect of Topical Corticosteroids on Dysphagia in Anterior Cervical Discectomy and Fusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOMPLETED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCervical Disc Herniation|Cervical Degenerative Disc Disease|Cervical Spondylotic Myelopathy|Dysphagia|Osteoarthritis of Cervical Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDRUG: Methylprednisolone Acetate|OTHER: Hemostatic Matrix Kit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHospital for Special Surgery, New York\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2015-08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11/12/2021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT04007094\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle-Armed Use of ViviGen Cellular Bone Matrix in Patients Undergoing Posterolateral Lumbar Surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTERMINATED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDegenerative Disc Disease|Spinal Stenosis|Spondylosis|Spondylolisthesis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOTHER: ViviGen Cellular Bone Matrix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOhio State University\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2/12/2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1/21/2022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT02347410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpineology Clinical Outcomes Trial: An IDE Investigation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOMPLETED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLumbar Degenerative Disc Disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDEVICE: SIFS graft containment device\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSpineology, Inc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1/22/2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3/4/2020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT01829997\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAssessment of nanOss Bioactive 3D in the Posterolateral Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOMPLETED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDegenerative Disc Disease|Spinal Stenosis|Spondylolisthesis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDEVICE: nanOss Bioactive 3D BVF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePioneer Surgical Technology, Inc.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2013-04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2018-04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT02667067\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInvestigation of the Simplify\u0026Acirc;\u0026reg; Cervical Artificial Disc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOMPLETED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCervical Degenerative Disc Disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDEVICE: Simplify Disc|DEVICE: Anterior Cervical Discectomy \u0026amp; Fusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNuVasive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2015-11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7/29/2021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT02704689\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAccuLIF\u0026Acirc;\u0026reg; PROSPECTIVE PATIENT OUTCOMES STUDY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTERMINATED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDegenerative Disc Disease|Spondylolisthesis, Grade 1|Retrolisthesis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDEVICE: AccuLIF expandable TLIF cage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eStryker Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6/8/2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1/19/2017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT03514277\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA Prospective Study to Compare Bupivacaine and Exparel Versus Bupivacaine or Exparel Alone for Postoperative Pain Relief\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTERMINATED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLow Back Pain|Lumbosacral Radiculopathy|Lumbar Disc Degeneration|Lumbar Disc Herniation|Stenosis|Spondylolisthesis|Spondylolysis|Deformity of Spine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDRUG: Exparel|DRUG: Bupivacaine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVirtua Health, Inc.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12/1/2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12/31/2019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT02412735\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePlacebo-controlled Study to Evaluate Rexlemestrocel-L Alone or Combined With Hyaluronic Acid in Participants With Chronic Low Back Pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCOMPLETED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDegenerative Disc Disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDRUG: Rexlemestrocel-L|DRUG: Rexlemestrocel-L\u0026thinsp;+\u0026thinsp;HA Mixture|DRUG: Placebo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMesoblast, Ltd.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3/6/2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6/15/2021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"4 Discussion","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Pharmacological Interventions\u003c/h2\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e4.1.1 Bupivacaine\u003c/h2\u003e \u003cp\u003eBupivacaine is a spinal anesthesia used in isobaric and hyperbaric forms (Moore, n.d.). It is administered intrathecally into the spine (Sng et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) bringing about a high frequency of satisfactory spinal nerve blockade and is widely used for all types of local anesthesia other than spinal anesthesia (Chambers, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e1982\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e4.1.2 Exparel\u003c/h2\u003e \u003cp\u003eExparel represents a liposome-encapsulated bupivacaine product available in the market. It has received approval for use as a local anesthetic in treating wounds and for certain types of perineural injections, though its use is contraindicated for epidural or intrathecal injections(Eisenach \u0026amp; Yaksh, n.d.). The formulation is developed through DepoFoam technology, facilitating prolonged drug release. The shift towards its broader utilization was significantly influenced by the opioid crisis, prompting medical professionals to explore alternative multimodal strategies for managing pain after surgery (Kaye et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section3\"\u003e \u003ch2\u003e4.1.3 Methylprednisolone Acetate\u003c/h2\u003e \u003cp\u003eMethylprednisolone acetate is a corticosteroid particulate suspension injected into the spine as a common pain management procedure. The rationale for its use is the inhibition of inflammation implicated in axial pain and radiculopathy (MacMahon et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Its dosage form contains excipients such as polythene glycol and miripirium (Schlatter et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section3\"\u003e \u003ch2\u003e4.1.4 Rexlemestrocel-L\u003c/h2\u003e \u003cp\u003eRexlemestrocel-L is currently under investigation as a product derived from human bone marrow, categorized as an allogeneic mesenchymal precursor cell (MPC) therapy, aimed at addressing critical and life-threatening inflammatory diseases (\u003cem\u003eRexlemestrocel-L\u003c/em\u003e, n.d.). Administering a single dose of Rexlemestrocel-L combined with hyaluronic acid (HA) into the lumbar disc is observed to notably decrease pain levels. This therapeutic approach utilizes advanced mesenchymal lineage cell therapy technology to tackle severe inflammation. It achieves this by secreting anti-inflammatory agents that effectively interact with and adjust various components of the immune system, thereby substantially mitigating the impact of inflammatory processes that contribute to pain (\u003cem\u003eFDA Grants Regenerative Medicine Advanced Therapy (Rmat) Designation for Rexlemestrocel-L in Chronic Low Back Pain\u003c/em\u003e, n.d.).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Medical Devices\u003c/h2\u003e \u003cdiv id=\"Sec20\" class=\"Section3\"\u003e \u003ch2\u003e4.2.1 AVS UniLIF PEEK Posterior Lumbar Cage\u003c/h2\u003e \u003cp\u003eAVS UniLIF is a posterior lumbar PEEK spacer crafted for use in both bilateral PLIF and oblique TLIF surgical techniques. Its design includes standard lengths suitable for bilateral PLIF procedures and extended lengths featuring obliquely angled lordotic profiles for unilateral TLIF methods. This design permits the insertion of a single spacer diagonally through the disc space to effectively achieve lordosis correction within the desired anterior-posterior dimension. The product offers a wide range of sizes in terms of length, height, and lordotic angles to accommodate diverse patient anatomical requirements. It features a spacious internal chamber designated for bone graft material, incorporates serrations on its upper and lower surfaces to support multi-directional fixation, and is designed with ergonomically contoured anterior edges alongside flat posterior edges to enhance its application (\u003cem\u003eAVS UniLIF\u003c/em\u003e, n.d.).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section3\"\u003e \u003ch2\u003e4.2.2 Simplify Disc\u003c/h2\u003e \u003cp\u003eThe Simplify\u0026reg; Cervical Artificial Disc, created by Nuvasive, Inc. based in San Diego, CA, is designed with PEEK (polyetheretherketone) endplates and a mobile core made from zirconia-toughened alumina ceramic. The endplates are coated with commercially pure titanium and are designed with concave articulating surfaces, while the ceramic core features two convex surfaces. This device is distinguished by its adaptability, offering endplates in small, medium, and large sizes, three variations in thickness that correspond to device heights of 4, 5, and 6 mm, and lordosis angles of 0\u0026deg; and 5\u0026deg;. A significant design element is the inclusion of a retention ring on the superior endplate to ensure core stability. Its versatility allows for accommodation of varying anatomical needs, positioning it as a significant advancement in the field of cervical artificial disc technology (Guyer et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section3\"\u003e \u003ch2\u003e4.2.3 nanOss Bioactive 3D BVF\u003c/h2\u003e \u003cp\u003eThe nanOss Bioactive 3D BVF is designed as a bone void filler that combines osteoconductive nano-structured hydroxyapatite (HA) with a specially engineered extracellular matrix bioscaffold to promote the natural formation of bone. In this innovative composition, nano-structured HA particles are integrated into a porous, gelatin-based foam. This product acts as a resorbable, porous calcium phosphate filler, creating a scaffold that encourages the growth of new bone tissue. It features an interconnected porosity that mimics the structure of human cancellous bone, making it an effective osteoconductive implant. The semi-rigid, three-dimensional structure contains porous hydroxyapatite granules embedded in a gelatin-based foam matrix derived from highly purified porcine collagen. Available in strip form, it allows for customization during surgical procedures. When hydrated at the site of implantation, nanOss Bioactive 3D becomes a compressible, elastic sponge, conforming to the shape of the bone defect to ensure optimal contact with the surrounding healthy bone. This product is sterilized using gamma irradiation and is intended for single-use only (\u003cem\u003enanOss_Bioactive_OUS_System_Overview\u003c/em\u003e, n.d.).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003e4.2.4 Stryker Tritanium Spinal System\u003c/h2\u003e \u003cp\u003eThe Tritanium PL Posterior Lumbar Cage represents a distinctive advancement in spinal implant technology. Crafted using AMagine Technology, our proprietary additive manufacturing approach, this hollow, rectangular implant boasts a unique configuration that combines solid and porous structures. Designed to cater to diverse patient anatomies, the Tritanium PL Cage is available in various widths, lengths, heights, and lordotic angles. Notable features include a spacious graft window and a sleek wedge nose, streamlining the insertion process into the disc space. With a threaded inserter connection, the implant ensures both rigid connectivity and precise control during insertion. Additionally, a circular dimple serves as an indicator for the correct insertion orientation, facilitating accurate positioning of the lordotic cages. This innovation in spinal cage design showcases a commitment to versatility, precision, and patient-specific adaptability (\u003cem\u003eTritanium PL\u003c/em\u003e, n.d.).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section3\"\u003e \u003ch2\u003e4.2.5 AccuLIF expandable TLIF cage\u003c/h2\u003e \u003cp\u003eThe AccuLIF lumbar interbody technology by Stryker Spine, part of the LITe (Less Invasive Technologies). This rectangular implant, utilizing a combination of solid and porous structures, allows for insertion at a smaller starting height and subsequent expansion based on patient anatomy, ensuring an optimal endplate-to-endplate fit. With features such as a large graft window and a surgeon-controlled hydraulic expansion mechanism operating in 1mm increments, the device emphasizes adaptability and precision in lumbar spinal interventions. Designed to preserve endplate integrity, minimize impaction forces, and protect neural elements, AccuLIF underscores a commitment to patient-centric outcomes in spinal surgery (\u003cem\u003eAccuLIF\u0026reg;\u003c/em\u003e, n.d.).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003e4.2.6 SIFS graft containment device\u003c/h2\u003e \u003cp\u003eThe Spineology Interbody Fusion System (SIFS) is an innovative lumbar intervertebral body fusion device designed to aid in the treatment of degenerative disc disease (DDD) and Grade 1 spondylolisthesis in skeletally mature patients. Manufactured by Spineology, Inc., the SIFS implant features a PET mesh bag that facilitates the containment of compatible allograft and autograft materials. This device is indicated for use as an adjunct to fusion in the lumbar spine, offering versatility with various widths, lengths, and heights. The system, when used in conjunction with posterior supplemental fixation, provides a comprehensive solution for fusion procedures. The SIFS implant, with its non-ferromagnetic and PET composition, ensures compatibility with various clinical settings. The device's unique design, combining efficiency and adaptability, underscores its role in advancing lumbar spinal interventions (\u003cem\u003eSpineology Interbody Fusion System\u003c/em\u003e, n.d.).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003e4.2.7 Nexxt Spine 3D-Printed Titanium Interbody Cages\u003c/h2\u003e \u003cp\u003eThe Nexxt Spine 3D-Printed Titanium Interbody Cages are innovative components within the NEXXT MATRIXX\u0026reg; SYSTEM. These cages, crafted from titanium using advanced 3D-printing technology, offer structural integrity and radiolucency. Designed for lumbar fusion procedures, they are compatible with supplemental fixation systems such as the Nexxt Spine Inertia\u0026reg; Pedicle Screw System, Inertia\u0026reg; MIS Pedicle Screw System, or Facet Fixx\u0026reg; Screw System. Patient positioning involves the prone position on a radiolucent spine table, and the surgical steps include discectomy, distraction, decompression, endplate preparation, and precise implant insertion. The 3D-printed titanium construction emphasizes durability and biocompatibility, contributing to successful fusion outcomes with minimal complications (\u003cem\u003eNEXXT MATRIXX\u0026reg; TLIF / TLIF Oblique Interbodies\u003c/em\u003e, n.d.).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section3\"\u003e \u003ch2\u003e4.2.8 HonourTM poly-ether-ether-ketone cage\u003c/h2\u003e \u003cp\u003eThe HONOUR\u0026reg; Spacer System for TLIF and tPLIF is a radiolucent cage constructed from medical-grade polyetheretherketone with tantalum markers, complying with ASTM F-2026 and ASTM F-560 standards. Patient positioning involves placing the patient in the prone position on a radiolucent spine table, minimizing ocular and nerve compression risks. Operative exposure is facilitated by fluoroscopic imaging and palpation, with HONOUR\u0026reg; TLIF/tPLIF Interbodies indicated for up to two contiguous levels in the lumbar spine. The surgical procedure includes disc space distraction, decompression, and endplate preparation. The lumbar straight and curved devices are chosen based on trial spacer fitting, ensuring disc height restoration. Implant placement involves autogenous bone graft material, attachment to the threaded inserter, and careful insertion, guided by fluoroscopic imaging. Bilateral approaches require attention to contralateral implant placement. Implant removal is achieved using the threaded implant inserter or a removal hook if needed (\u003cem\u003eHONOUR \u0026reg; tPLIF / TLIF Interbodies\u003c/em\u003e, n.d.).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec28\" class=\"Section3\"\u003e \u003ch2\u003e4.2.9 Aviator Anterior Cervical Plating System\u003c/h2\u003e \u003cp\u003eThe Aviator Anterior Cervical Plating System is distinguished by its innovative double screw locking mechanism, which allows for extensive screw angulation and features streamlined instrumentation. Its primary locking mechanism utilizes a spring-loaded bar that automatically snaps into place over the screws, ensuring they are locked with both visual and tactile indicators. The system incorporates both fixed and variable angle screws, supporting a wide range of bone screw fixation techniques. Made from Titanium Alloy, the plate is 2.5mm in thickness and 17.4mm in width, and it is designed with a lordotic curve, windows for graft viewing, and screws that are self-tapping and self-drilling, available in diameters of 4.0mm and 4.35mm, with color coding for straightforward identification. Proper patient positioning and precise incision placement are vital, followed by a detailed discectomy or corpectomy, and careful removal of any obstructive bony structures. The Aviator System is crafted to offer surgeons a flexible and effective approach to anterior cervical plating, adapting seamlessly to a variety of surgical methods and patient anatomical requirements (\u003cem\u003eAviator\u0026reg; Anterior Cervical Plating System\u003c/em\u003e, n.d.).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec29\" class=\"Section2\"\u003e \u003ch2\u003e4.3 Biological and Other interventions\u003c/h2\u003e \u003cdiv id=\"Sec30\" class=\"Section3\"\u003e \u003ch2\u003e4.3.1 Cellentra VCBM\u003c/h2\u003e \u003cp\u003eBiomet Inc.'s Cellentra VCBM represents a state-of-the-art bone growth enhancer utilizing AlloStem Stem Cell technology, derived from the adipose tissue of adult humans. This allograft undergoes a rigorous processing protocol to preserve its regenerative capabilities, aiming to promote bone formation and accelerate the healing process. Adipose tissue is recognized for its abundance of stem cells, which some research highlights as a key stem cell reservoir in the body. Cellentra VCBM sets itself apart by offering a potent mix of factors conducive to bone healing, including an osteoconductive framework that supports the growth of osteogenic cells and mesenchymal stem cells (MSCs), both known for their osteoinductive potential. The graft is enriched with critical growth factors such as bone morphogenetic proteins (BMP-2, -4, -7), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1), and fibroblast growth factor (FGF). With a cancellous bone matrix featuring a trabecular structure that is interconnected, Cellentra VCBM optimizes osteoconductivity, thereby facilitating enhanced bone regeneration (Wei et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2014\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec31\" class=\"Section3\"\u003e \u003ch2\u003e4.3.2 NuCel\u003c/h2\u003e \u003cp\u003eNuCel\u0026reg; is a cryogenically preserved amniotic suspension allograft, obtained from the human amniotic membrane (AM) and cells within the amniotic fluid, specifically processed to preserve its biological activity. When used in conjunction with a bone allograft for lumbar interbody fusion surgeries, the integration of NuCel\u0026reg; has been shown to achieve a clinical fusion rate that rivals that of traditional lumbar interbody fusion techniques (Etchebarne et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec32\" class=\"Section3\"\u003e \u003ch2\u003e4.3.3 Demineralized Bone Matrix\u003c/h2\u003e \u003cp\u003eDemineralized bone matrix (DBM) is a well-established biomaterial and medically approved device for addressing bone defects, boasting an extensive history of application across various clinical settings. Sourced from human bone, DBM preserves the bone's inherent protein content, along with minimal quantities of calcium compounds, inorganic phosphates, and residual cellular material. It is offered in multiple formats, including putty, paste, sheets, and malleable pieces, acting as a biodegradable scaffold that promotes the release of powerful osteogenic substances such as growth factors. DBM is recognized for its osteoconductive and osteoinductive capabilities, fostering new bone growth, expediting the healing process, and opening avenues for advancements in orthopedic restoration and regenerative medicine (Gruskin et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2012\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec33\" class=\"Section3\"\u003e \u003ch2\u003e4.3.4 BIO4 Bone Matrix\u003c/h2\u003e \u003cp\u003eThe BIO4 Bone Matrix is a cryogenically preserved viable bone matrix that encompasses the natural matrix, endogenous osteoblasts, mesenchymal stem cells (MSCs), as well as osteoinductive and angiogenic growth factors (Lin et al., 2020). This product is tailored for patients undergoing Anterior Cervical Discectomy and Fusion (ACDF) procedures. Its development targets the fulfillment of the four essential properties necessary for effective bone healing and regeneration: osteoconductivity, osteoinductivity, osteogenicity, and angiogenicity. BIO4 serves as an alternative to autografts, aiming to minimize the risk of complications that can arise from graft harvesting (\u003cem\u003eResearch Proposal\u003c/em\u003e, 2014).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec34\" class=\"Section2\"\u003e \u003ch2\u003e4.4 Conclusion\u003c/h2\u003e \u003cp\u003eThe examination of intervertebral disc degeneration (IVD) trial protocols has offered a comprehensive insight into contemporary trends in spinal interventions, shaping a dynamic landscape dedicated to optimizing patient outcomes. This synthesis explores key findings in pharmacological interventions (drugs), medical devices, and biological interventions, drawing upon pertinent research in the field of spinal healthcare.\u003c/p\u003e \u003cp\u003eA notable trend is the significant shift towards multimodal pain management, acknowledging and addressing the opioid epidemic. Alternatives like bupivacaine and Exparel have gained prominence, underscoring efforts to minimize opioid dependence while ensuring efficacious analgesia. The integration of innovative drug delivery systems, exemplified by liposome-encapsulated formulations like Exparel, highlights a commitment to precision and sustained therapeutic efficacy. Additionally, the investigational use of Rexlemestrocel-L, a mesenchymal precursor cell product, signifies a transformative phase by not only alleviating symptoms but actively contributing to tissue repair and regeneration.\u003c/p\u003e \u003cp\u003eThe medical devices in spinal interventions demonstrate a commitment to precision and personalized treatment strategies. Noteworthy examples include the AVS UniLIF posterior lumbar cage and the Simplify Disc cervical artificial disc, showcasing the trend towards tailoring devices to individual anatomies for optimal outcomes in spinal surgery. The incorporation of 3D-printed titanium in devices like the Tritanium PL Posterior Lumbar Cage represents a convergence of materials science and surgical innovation, enhancing structural integrity and bio integration potential. Minimally invasive technologies, such as the AccuLIF expandable TLIF cage, underscore a commitment to patient safety and reduced surgical invasiveness.\u003c/p\u003e \u003cp\u003eThe realm of biological interventions unfolds with promising advancements such as Cellentra VCBM, a bone growth substitute leveraging AlloStem Stem Cell technology. This innovative approach stimulates bone growth and facilitates healing by incorporating essential growth factors within an osteoconductive scaffold. NuCel, an amniotic suspension allograft, demonstrates high clinical fusion rates in lumbar interbody fusion, highlighting its efficacy comparable to conventional procedures. The use of cryopreserved viable bone matrix, as seen in BIO4 Bone Matrix, showcases a holistic approach fulfilling crucial characteristics for bone repair and regeneration in spine surgery.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec35\" class=\"Section2\"\u003e \u003ch2\u003e4.5 Implications for Research\u003c/h2\u003e \u003cp\u003eThe divergence observed in current intervertebral disc degeneration (IVD) trial protocols underscores the critical need for standardization. The identified variations, ranging from inclusion criteria to outcome measures, emphasize the importance of establishing consensus on key elements. Standardized protocols not only enhance the comparability of study outcomes but also facilitate meta-analyses, systematic reviews, and cumulative knowledge generation. A crucial implication is the encouragement of an open-access culture in sharing clinical trial protocols, promoting transparency and collaboration. By fostering a shared understanding of interventions and methodological nuances, this approach not only expedites individual studies but also contributes to the collective advancement of spinal healthcare research. The call for standardization and open-access protocols reflects a commitment to elevating the rigor, reproducibility, and impact of future investigations in the field.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of Interest:\u003c/h2\u003e \u003cp\u003enone declared.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis project was supported by the Marie Skłodowska-Curie International Training Network \u0026ldquo;Disc4All\u0026rdquo; under grant agreement #955735.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e\u003cem\u003eAccuLIF\u0026reg;\u003c/em\u003e. (n.d.). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://thespinemarketgroup.com/wp-content/uploads/2020/07/Acculif.SGT-Stryker.pdf\u003c/span\u003e\u003cspan address=\"https://thespinemarketgroup.com/wp-content/uploads/2020/07/Acculif.SGT-Stryker.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdams MA, Roughley PJ (2006) What is intervertebral disc degeneration, and what causes it? Spine 31(18):2151\u0026ndash;2161. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/01.brs.0000231761.73859.2c\u003c/span\u003e\u003cspan address=\"10.1097/01.brs.0000231761.73859.2c\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAshinsky B, Smith HE, Mauck RL, Gullbrand SE (2021) Intervertebral disc degeneration and regeneration: A motion segment perspective. Eur Cells Mater 41:370\u0026ndash;380. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.22203/eCM.v041a24\u003c/span\u003e\u003cspan address=\"10.22203/eCM.v041a24\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003cem\u003eAviator\u0026reg; Anterior Cervical Plating System\u003c/em\u003e. (n.d.). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://thespinemarketgroup.com/wp-content/uploads/2021/12/Aviator-Cervical-Plate-SGT.Stryker.pdf\u003c/span\u003e\u003cspan address=\"https://thespinemarketgroup.com/wp-content/uploads/2021/12/Aviator-Cervical-Plate-SGT.Stryker.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAVS UniLIF. (n.d.). Retrieved January 17 (2024) from \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.stryker.com/us/en/spine/products/avs-unilif.html\u003c/span\u003e\u003cspan address=\"https://www.stryker.com/us/en/spine/products/avs-unilif.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChambers WA (1982) INTRATHECAL BUPIVACAINE. Br J Anaesth 54(8):799\u0026ndash;801. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/bja/54.8.799\u003c/span\u003e\u003cspan address=\"10.1093/bja/54.8.799\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan A-W, Tetzlaff JM, G\u0026oslash;tzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hr\u0026oacute;bjartsson A, Schulz KF, Parulekar WR, Krleža-Jerić K, Laupacis A, Moher D (2013) SPIRIT 2013 explanation and elaboration: Guidance for protocols of clinical trials. BMJ 346:e7586. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/bmj.e7586\u003c/span\u003e\u003cspan address=\"10.1136/bmj.e7586\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChu G, Shi C, Wang H, Zhang W, Yang H, Li B (2018) Strategies for Annulus Fibrosus Regeneration: From Biological Therapies to Tissue Engineering. Front Bioeng Biotechnol 6:90. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fbioe.2018.00090\u003c/span\u003e\u003cspan address=\"10.3389/fbioe.2018.00090\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCostăchescu B, Niculescu A-G, Teleanu RI, Iliescu BF, Rădulescu M, Grumezescu AM, Dabija MG (2022) Recent Advances in Managing Spinal Intervertebral Discs Degeneration. Int J Mol Sci 23(12):6460. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/ijms23126460\u003c/span\u003e\u003cspan address=\"10.3390/ijms23126460\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEisenach JC, Yaksh TL (n.d.). \u003cem\u003eSpinal Exparel\u0026reg;dan extended duration of preclinical study needed\u003c/em\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEtchebarne M, Fricain J-C, Kerdjoudj H, Di Pietro R, Wolbank S, Gindraux F, Fenelon M (2021) Use of Amniotic Membrane and Its Derived Products for Bone Regeneration: A Systematic Review. Front Bioeng Biotechnol 9:661332. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fbioe.2021.661332\u003c/span\u003e\u003cspan address=\"10.3389/fbioe.2021.661332\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003cem\u003eFDA Grants Regenerative Medicine Advanced Therapy (Rmat) Designation for Rexlemestrocel-L in Chronic Low Back Pain\u003c/em\u003e. (n.d.). BioSpace. Retrieved January 17, (2024) from \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.biospace.com/article/fda-grants-regenerative-medicine-advanced-therapy-rmat-designation-for-rexlemestrocel-l-in-chronic-low-back-pain-/\u003c/span\u003e\u003cspan address=\"https://www.biospace.com/article/fda-grants-regenerative-medicine-advanced-therapy-rmat-designation-for-rexlemestrocel-l-in-chronic-low-back-pain-/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGruskin E, Doll BA, Futrell FW, Schmitz JP, Hollinger JO (2012) Demineralized bone matrix in bone repair: History and use. Adv Drug Deliv Rev 64(12):1063\u0026ndash;1077. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.addr.2012.06.008\u003c/span\u003e\u003cspan address=\"10.1016/j.addr.2012.06.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuyer RD, Coric D, Nunley PD, Sasso RC, Musacchio M, Bae HW, Peloza JH, Ohnmeiss DD (2021) Single-Level Cervical Disc Replacement Using a PEEK-on-Ceramic Implant: Results of a Multicenter FDA IDE Trial With 24-Month Follow-up. Int J Spine Surg 15(4):633\u0026ndash;644. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.14444/8084\u003c/span\u003e\u003cspan address=\"10.14444/8084\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003cem\u003eHONOUR \u0026reg; tPLIF / TLIF Interbodies\u003c/em\u003e. (n.d.). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://nexxtspine.showpad.com/share/8xE9u20GtcxeBmRjFnHXu\u003c/span\u003e\u003cspan address=\"https://nexxtspine.showpad.com/share/8xE9u20GtcxeBmRjFnHXu\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaye AD, Armstead-Williams C, Hyatali F, Cox KS, Kaye RJ, Eng LK, Anwar F, Patel MA, Patil PV, S., Cornett EM (2020) Exparel for Postoperative Pain Management: A Comprehensive Review. Curr Pain Headache Rep 24(11):73. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s11916-020-00905-4\u003c/span\u003e\u003cspan address=\"10.1007/s11916-020-00905-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Z, Fu C (2022) Application of single and cooperative different delivery systems for the treatment of intervertebral disc degeneration. \u003cem\u003eFrontiers in Bioengineering and Biotechnology\u003c/em\u003e, \u003cem\u003e10\u003c/em\u003e. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.frontiersin.org/articles/\u003c/span\u003e\u003cspan address=\"https://www.frontiersin.org/articles/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fbioe.2022.1058251\u003c/span\u003e\u003cspan address=\"10.3389/fbioe.2022.1058251\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMacMahon PJ, Huang AJ, Palmer WE (2016) Spine Injectables: What Is the Safest Cocktail? Am J Roentgenol 207(3):526\u0026ndash;533. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2214/AJR.16.16379\u003c/span\u003e\u003cspan address=\"10.2214/AJR.16.16379\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoore DC (n.d.). Spinal Anesthesia: Bupivacaine Compared with Tet racaine. \u003cem\u003eANESTHESIA AND ANALGESIA\u003c/em\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003cem\u003enanOss_Bioactive_OUS_System_Overview\u003c/em\u003e. (n.d.). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.lifehealthcare.com.au/wp-content/uploads/2017/06/nanOss_Bioactive_OUS_System_Overview.pdf\u003c/span\u003e\u003cspan address=\"https://www.lifehealthcare.com.au/wp-content/uploads/2017/06/nanOss_Bioactive_OUS_System_Overview.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNEXXT, MATRIXX\u0026reg; \u003cem\u003eTLIF / TLIF Oblique Interbodies\u003c/em\u003e. (n.d.). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://thespinemarketgroup.com/wp-content/uploads/2020/08/Matrixx-Lumbar-STG-Nexxt-Spine.pdf\u003c/span\u003e\u003cspan address=\"https://thespinemarketgroup.com/wp-content/uploads/2020/08/Matrixx-Lumbar-STG-Nexxt-Spine.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOhnishi T, Iwasaki N, Sudo H (2022) Causes of and Molecular Targets for the Treatment of Intervertebral Disc Degeneration: A Review. Cells 11(3):394. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/cells11030394\u003c/span\u003e\u003cspan address=\"10.3390/cells11030394\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeng Y, Qing X, Shu H, Tian S, Yang W, Chen S, Lin H, Lv X, Zhao L, Chen X, Pu F, Huang D, Cao X, Shao Z (2021) Proper animal experimental designs for preclinical research of biomaterials for intervertebral disc regeneration. Biomaterials Translational 2(2):91\u0026ndash;142. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.12336/biomatertransl.2021.02.003\u003c/span\u003e\u003cspan address=\"10.12336/biomatertransl.2021.02.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003cem\u003eResearch Proposal\u003c/em\u003e. (2014)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRexlemestrocel (ed) (n.d.). Retrieved January 17, 2024, from \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://go.drugbank.com/drugs/DB17606\u003c/span\u003e\u003cspan address=\"https://go.drugbank.com/drugs/DB17606\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchlatter J, Nguyen D, Zamy M, Kabiche S, Fontan J-E, Cisternino S (2019) Safety of intrathecal route: Focus to methylprednisolone acetate (Depo-Medrol) use. Eur Spine J 28(1):21\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00586-017-5387-x\u003c/span\u003e\u003cspan address=\"10.1007/s00586-017-5387-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSng BL, Siddiqui FJ, Leong WL, Assam PN, Chan ES, Tan KH, Sia AT (2016) Hyperbaric versus isobaric bupivacaine for spinal anaesthesia for caesarean section. \u003cem\u003eCochrane Database of Systematic Reviews\u003c/em\u003e, \u003cem\u003e2016\u003c/em\u003e(9). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/14651858.cd005143.pub3\u003c/span\u003e\u003cspan address=\"10.1002/14651858.cd005143.pub3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u003cem\u003eSpineology Interbody Fusion System\u003c/em\u003e. (n.d.). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.accessdata.fda.gov/cdrh_docs/pdf20/DEN200010.pdf\u003c/span\u003e\u003cspan address=\"https://www.accessdata.fda.gov/cdrh_docs/pdf20/DEN200010.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTritanium PL. (n.d.). Retrieved January 17 (2024) from \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.stryker.com/us/en/spine/products/tritanium-pl.html\u003c/span\u003e\u003cspan address=\"https://www.stryker.com/us/en/spine/products/tritanium-pl.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham jerry, Ackerman I, Aggarwal R, Ahn SY, Ali MK, AlMazroa MA, Alvarado M, Anderson HR, Anderson LM, Murray CJL (2012) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990\u0026ndash;2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet (London England) 380(9859):2163\u0026ndash;2196. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0140-6736(12)61729-2\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(12)61729-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei C-C, Lin AB, Hung S-C (2014) Mesenchymal Stem Cells in Regenerative Medicine for Musculoskeletal Diseases: Bench, Bedside, and Industry. Cell Transplant 23(4\u0026ndash;5):505\u0026ndash;512. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3727/096368914X678328\u003c/span\u003e\u003cspan address=\"10.3727/096368914X678328\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu A, March L, Zheng X, Huang J, Wang X, Zhao J, Blyth FM, Smith E, Buchbinder R, Hoy D (2020) Global low back pain prevalence and years lived with disability from 1990 to 2017: Estimates from the Global Burden of Disease Study 2017. Annals Translational Med 8(6):299\u0026ndash;299. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.21037/atm.2020.02.175\u003c/span\u003e\u003cspan address=\"10.21037/atm.2020.02.175\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXin J, Wang Y, Zheng Z, Wang S, Na S, Zhang S (2022) Treatment of Intervertebral Disc Degeneration. Orthop Surg 14(7):1271\u0026ndash;1280. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/os.13254\u003c/span\u003e\u003cspan address=\"10.1111/os.13254\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Pompeu Fabra University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Intervertebral disc degeneration (IVD), chronic back pain, clinical trial protocols,interventions, PRISMA guidelines","lastPublishedDoi":"10.21203/rs.3.rs-5017042/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5017042/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e \u003cp\u003eIntervertebral disc degeneration (IVD) is a common condition causing chronic back pain and disability. Despite its global prevalence, the knowledge about treatment options that can be appraised is limited, and some current interventions often fail to provide enduring relief. This review explores IVD management strategies, including conservative, non-surgical, surgical, and regenerative approaches. Available clinical trial protocols were systematically analyzed to identify trends and knowledge gaps.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis paper conducted an examination of clinical trial protocols with the aim of showcasing the strategies employed by researchers to address intervertebral disc degeneration. Additionally, it enumerates both the primary and secondary outcomes, along with their respective measurement methods. This analysis seeks to identify gaps in existing knowledge and make valuable contributions to future research endeavors. To ensure a structured approach, the study adheres to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews (PRISMA).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOut of the selected studies with protocols (N\u0026thinsp;=\u0026thinsp;14) focusing on intervertebral disc degeneration, our analysis revealed that 3 (21%) were drug interventions, 3 (21%) were biological interventions, 7 (50%) were device interventions, and 1 (1%) was categorized as other. A chi-square goodness-of-fit test was employed to examine the distribution of these intervention types against an expected equal distribution. The statistical analysis yielded a chi-square statistic of 5.43, corresponding to a p-value of approximately 0.143. This indicates that, within the scope of our review, the distribution of intervention types does not significantly deviate from what might be expected by chance alone (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), suggesting a relatively balanced exploration of intervention strategies in the existing literature.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eWe observed that for the drug interventions, there was a shift toward multimodal pain management, especially after the opioid epidemic with alternatives such as liposome-encapsulated formulations; For medical devices, focus is on personalized and non-invasive technologies while in biological interventions, regenerative medicine is hugely stressed. There however is a huge divergence in the content and quality of Intervertebral disc degeneration clinical trial protocols, necessitating an investigation into the standardization of these protocols. This is because the content and quality of the protocol has a direct impact on the quality of data generated.\u003c/p\u003e","manuscriptTitle":"A Review of Intervertebral Disc Degeneration Clinical Trial Protocols","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-04 21:20:56","doi":"10.21203/rs.3.rs-5017042/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b7e3677c-d6f3-4f6e-8f2c-cdebc292fefa","owner":[],"postedDate":"September 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":36949502,"name":"Bioinformatics"}],"tags":[],"updatedAt":"2024-09-04T21:20:56+00:00","versionOfRecord":[],"versionCreatedAt":"2024-09-04 21:20:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5017042","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5017042","identity":"rs-5017042","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}