Functional Competency of a Novel 2-Ply Vacuum-Pressed Biological Scaffold for Posterior Mitral Valve Repair

Functional Competency of a Novel 2-Ply Vacuum-Pressed Biological Scaffold for Posterior Mitral Valve Repair | 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 Article Functional Competency of a Novel 2-Ply Vacuum-Pressed Biological Scaffold for Posterior Mitral Valve Repair Johannes H. Jedrzejczyk, Frederik T. Andersen, Alexander Emil Kaspersen, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7766713/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Jan, 2026 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Objective This study assessed the feasibility of posterior mitral valve leaflet and subvalvular reconstruction in an acute porcine model using a novel 2-ply vacuum-pressed small intestinal submucosal extracellular matrix (SIS-ECM) patch. Methods Reconstruction was performed in an acute 80-kg porcine model (n = 7), using a novel 2-ply vacuum-pressed SIS-ECM (CorMatrix®) patch for posterior mitral reconstruction. Echocardiography and left ventricular pressure were assessed pre- and post-interventional. Sonomicrometry was used to evaluate the geometry and valve dynamics. Results The reconstructed mitral valves were all fully competent. The peak left atrial pressure at baseline and post-reconstruction was 9.9 (1.1) vs 9.9 (1.0) mmHg, p = 0.676, diff = 0.002 mmHg, 95% CI: [-1.06;1.05], and the mean trans-mitral pressure difference was 4.5 (2.3) vs 4.1 (2.3) mmHg, p = 0.063, diff = -0.40, 95% CI: [-2,73;1.93] The out-of-plane characteristics and subvalvular geometry of the mitral valve were preserved after reconstruction. Slight atrial bending of the reconstructed posterior leaflet and systolic annular ballooning were observed. Conclusions In an acute porcine model, we successfully reconstructed the posterior mitral valve and subvalvular apparatus using our modified 2-ply vacuum-pressed SIS-ECM patch. The bioscaffold demonstrated short-term durability in vivo, warranting further investigation of its long-term durability. Health sciences/Cardiology Health sciences/Diseases Health sciences/Medical research Mitral valve mitral valve repair patch repair bioscaffold small intestinal submucosal extracellular matrix. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Surgical intervention is recommended for patients with severe mitral valve (MV) regurgitation, particularly when conservative treatment is insufficient. MV repair has become more common over the past five decades and is favoured over replacement due to better long-term clinical outcomes ( 1 ). However, a successful repair requires sufficient pliable MV tissue ( 2 ), often unavailable in patients with rheumatic valve disease, degenerative MV disease, or extensive calcification, necessitating patch repair for adequate reconstruction ( 3 , 4 ). An effective MV patch material must meet several criteria, including being non-infectious, non-thrombogenic, and non-immunogenic, as well as being pliable and calcification-resistant, while supporting cell growth ( 5 ). Small intestinal submucosal extracellular matrix (SIS-ECM) has emerged as a promising material for MV patches due to its biocompatibility and mechanical properties, which align well with these requirements. In prior studies, our group successfully reconstructed the posterior MV leaflet and chordae tendineae in an acute porcine model using 2-ply lyophilised SIS-ECM ( 6 ). However, the material lacked sufficient suture retention strength, necessitating double folding at the anchoring points ( 6 ), which could interfere with the degeneration and remodelling process of the bioscaffold. Additionally, clinical studies suggest that lyophilised SIS-ECM may lack durability, with patch failure and recurrent MV regurgitation observed in some instances ( 7 , 8 ). The vacuum-pressing method differs from lyophilisation. In a previous study, we found that vacuum-pressed SIS-ECM exhibits greater mechanical strength than the lyophilised version and is feasible for posterior MV reconstruction in vitro ( 9 ). We hypothesise that 2-ply vacuum-pressed SIS-ECM possesses the properties needed for an ideal MV patch material, potentially allowing for posterior MV leaflet and chordae tendineae reconstruction in vivo. Thus, the present study aimed to evaluate our novel patch design for posterior MV and subvalvular reconstruction using 2-ply vacuum-pressed SIS-ECM in an acute porcine model. Materials & Methods Study Design This experimental in vivo study was conducted at the Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Each pig served as its own control, with preoperative baseline and post-interventional measurements, eliminating the need for a separate control group. This design reduced the number of animals used by 50%, adhering to the 3 R’s principle of replacement, reduction, and refinement (10). Ethical statement The study complied with the National Guidelines for Experimental Animal Research and was approved by the Danish Inspectorate of Animal Experimentation (No. 2016-15-0201-01132). Reporting was done in accordance with the ARRIVE guidelines. Animals Seven female 80-kg pigs (mixed Duroc and Danish Landrace-Yorkshire), sourced from Aarhus University, Aarhus, Denmark, were used. The animal model has been previously described in detail (11). Patch Material The posterior MV patch was fashioned from a 100 x 70 mm sheet of 2-ply vacuum-pressed SIS-ECM (CorMatrix®, Cardiovascular Inc., Alpharetta, GA, USA), illustrated in Fig. 1a-b. The vacuum-pressed SIS-ECM material and the patch design have been described in an earlier study (9). Instrumentation Invasive pressure measurements were obtained using Mikro-Tip pressure catheters (SPR-350S, Millar Instruments, Houston, TX, USA). Baseline and post-interventional MV geometry and leaflet mobility were assessed with epicardial echocardiography (Vivid E9, GE Vingmed Ultrasound AS., Horten, Norway). Eleven piezoelectric 2 mm sonomicrometry crystals (Sonometrics Corp., London, Canada) were used to assess the annular and subvalvular geometry (12). Surgical Procedure Transportation, handling, and anaesthesia have been previously described (11,13). Anaesthesia was maintained by continuous intravenous administration of Propofol (4.375 mg/kg/h), Fentanyl (6µg/kg/h), and Rocuronium (3.125 mg/kg/h). The heart was exposed through a median sternotomy, and the pig was heparinised with 50.000 IU of heparin. Baseline measurements, including epicardial echocardiography and intracardiac and intra-arterial pressure measurements, were performed before the establishment of cardiopulmonary bypass and cardiac arrest by cold blood cardioplegia. The MV was exposed via a left atriotomy. Four 5-0 Optilene® sutures (B. Braun, Melsungen, Germany) were placed in the annulus at the anterolateral commissure, the P1-P2 indentation, the P2-P3 indentation, and the posteromedial commissure. The posterior MV leaflet was excised at the annular level, and the associated chordae tendineae were transected at the papillary muscle heads. Two additional 5-0 Optilene® sutures were placed in the fibrous portion of each papillary muscle head, oriented anteriorly and posteriorly. The implantation technique is illustrated in Fig. 1c-f. The P1 and P3 segments of the patch each contained two anchoring points, connected to the anterolateral and posteromedial papillary muscles, respectively. The anchoring points within each segment were spaced 1 cm apart and secured to the papillary muscle heads using three continuous suture loops spanning 2-3 mm, before the patch was parachuted into place. The oversized patch was evenly distributed across the four annular landmark sutures and fixed using a running interlocking suture. It was then attached to the anterior leaflet with a plicated suture at each commissure. No prosthetic ring was implanted. The left atrium was closed with a 4-0 Optilene® running suture, after which the animal was weaned from cardiopulmonary bypass and re-perfused. Off-pump interventional echocardiography, intracardiac, and intra-arterial pressure recordings were performed under spontaneous cardiac activity. Cardiopulmonary bypass and cardioplegic arrest were reinitiated, and the left atrium was reopened to place eight annular and three ventricular sonomicrometry crystals (Fig. 2). Annular wires were exteriorised through the atrial wall, and ventricular wires through the apex. Following atrial closure, the animal was weaned from bypass, re-perfused, and sonomicrometry measurements were recorded. Euthanasia was performed under continued anaesthesia via an intravenous overdose of pentobarbital. All procedures were performed by the same surgeon (JHJ) under identical conditions over three weeks. Data Acquisition & Data Analysis Signal acquisition, synchronisation, and analysis of haemodynamic, echocardiographic, and sonometric data were performed according to the same protocol established in our previous study (11). This included processing of pressure waveforms, quantification of leaflet motion, and measurements of annular geometry. Statistical Analysis Following the assessment of normality, results are presented as mean with standard deviation (SD). Normality was assessed by inspecting quantile plots and tested using the Shapiro-Wilk test. Pressure data were analysed using a mixed-effects model with group (baseline, intervention) as a fixed effect and pig as a random effect. Echocardiographic and hemodynamic parameters obtained from echocardiography were compared using another mixed-effects model with group as a fixed effect and pig as a random effect. Models were fitted using restricted maximum likelihood, and the Kenward-Roger correction method was applied to reduce small-sample bias (14). The homoscedasticity of residuals was checked by plotting them as a function of predicted values. The normality of residuals and random effects was checked by inspection of quantile plots of residuals and best linear unbiased predictors, respectively. Post hoc pairwise comparisons of all variables between groups were performed using a 2-tailed least-squares means pairwise t-test, with an alpha level of 0.05. The statistical models were developed with the Biostatistical Advisory Service (BIAS), Aarhus University, Aarhus, Denmark. Statistical analyses were performed using SAS ® Enterprise Guide ® software, version 7.1 (SAS, Institute Inc., Cary, NC, USA). Results All reconstructed valves showed preserved haemodynamic function and geometric properties in all subjects. Haemodynamic Results Mean peak left atrial pressure (SD) at baseline and after repair showed no statistically significant difference: 9.9 (1.1) vs 9.9 (1.0) mmHg, p = 0.676, diff = 0.002 mmHg, 95% CI: [-1.06;1.05]. The mean MV pressure difference (SD) decreased slightly from 4.5 (2.3) vs 4.1 (2.3) mmHg, p = 0.063, diff = -0.40, 95% CI: [-2,73;1.93]. These findings indicate no evidence of mitral regurgitation or stenosis. The mean ejection fraction (SD) showed no statistically significant difference before and after reconstruction: 56.6 (12.3) vs. 63.7 (1.3) %, p = 0.152, diff = 7.10, 95% CI: [-1.75; 15.95]. Echocardiographic Results Fig. 3 displays echocardiographic images of the reconstructed MV, with geometric parameters summarised in Table 1. Echocardiography confirmed a fully functional MV in all subjects, with no evidence of regurgitation, stenosis or systolic anterior motion following reconstruction. Posterior leaflet repair led to a statistically significant reduction in septal-lateral annular diameter and a statistically significant increase in posterior leaflet length at end-diastole, while anterior leaflet length remained unchanged. Posterior billowing height was statistically significantly reduced, with no corresponding change in the anterior leaflet. Coaptation length and tenting height were both statistically significantly increased after reconstruction. Sonomicrometry Results Fig. 4 present in-plane geometric measurements, including annular area, circumference, septal-lateral distance, and commissure-commissure distance. Fig. 5a-d illustrates out-of-plane MV annular geometric results, including annular height, annular height-to-commissural width ratio, annular segmental distance, and the annular crystal distances at end-systole to the least square plane as an expression of the saddle shape of the MV. Subvalvular geometric results shown in Fig. 5d-f include cyclic papillary muscle distances and their respective distance to the annulus. Fig. 6 illustrates annular segmental circumferential changes from end-diastole to end-systole, with a colour scale indicating regional systolic circumferential changes. Discussion Posterior MV leaflet pathology can convert a “simple repair” to a challenging surgical procedure (2,4), and a total MV replacement may be warranted in cases with extensive damage to the posterior MV leaflet (2). While prior in vitro (15) and animal studies (6) on 2-ply lyophilised SIS-ECM have shown promising results, clinical data have raised concerns about its long-term efficacy and durability (7,8). This acute porcine study examined transvalvular pressure differences, MV annular and subvalvular geometry, as well as valve dynamics before and after reconstruction of the posterior MV leaflet and subvalvular apparatus with 2-ply vacuum-pressed SIS-ECM. The posterior MV and subvalvular apparatus were fully functional, with no regurgitant jets on the colour Doppler echocardiography and no statistically significant change in peak left atrial pressure. Furthermore, no post-reconstruction indication of stenosis was found, as a similar mean pressure difference across the MV was observed. Double folding the material at the anchoring points was omitted, based on findings from our previous in vitro study of 2-ply vacuum-pressed SIS-ECM (9). Considering the earlier in vitro findings and the current in vivo findings, the vacuum-pressed SIS-ECM exhibits stronger biomechanical characteristics compared to the lyophilised SIS-ECM, offering several advantages. First, it simplifies the surgical technique by eliminating the need for double folding, potentially reducing operative time. Second, it may reduce the risk of thrombosis, which could arise from the potential space created between double-folding the material. Third, the material preserves its intrinsic properties for degeneration and recellularisation. However, further studies are needed to confirm whether its suture retention strength remains sufficient over time. Echocardiographic parameters were comparable to those observed in the human heart (16), and post-repair imaging demonstrated an anatomical and functional appearance similar to the native MV. A statistically significant reduction in the septal-lateral annular dimension was observed following repair. Although annular downsizing in this plane may reduce the left ventricular outflow tract area and increase the risk of systolic anterior motion, neither echocardiographic imaging nor catheter-based pressure measurements revealed evidence of this. Despite the reduced septal-lateral diameter, the mitral annulus exhibited similar systolic contraction before and after repair, indicating preserved cyclic annular dynamics. The billowing height of the native anterior MV leaflet was preserved following reconstruction, whereas the posterior leaflet showed a statistically significant reduction. This reduction was attributed to atrial bending of the reconstructed posterior leaflet, as observed on echocardiography. The deformation likely results from excess tissue and the absence of intermediate and basal chordae, which usually counteract systolic pressure directed toward the left atrium (6). Atrial bending of the posterior leaflet is a known limitation of this surgical technique and may alter left ventricular flow dynamics and stress distribution across the MV apparatus. Further studies are needed to evaluate the long-term biomechanical and functional implications of this phenomenon. Changes in annular area, circumference, and commissure-commissure distance confirmed that the size and dynamic behaviour of the reconstructed MV were generally compatible with those reported in native valve studies (17,18). Both echocardiography and sonomicrometry demonstrated a reduction in the septal-lateral dimension compared with baseline and native valves (17,19). However, during systole, an increase in annular area, circumference, and commissure-commissure distance was observed relative to native measurements, indicating an unphysiological annular widening. This was further supported by segmental analysis, which revealed systolic widening of the posterior annulus and corresponding circumferential deformation. A similar pattern was previously observed in our animal study using lyophilised 2-ply SIS-ECM for posterior leaflet reconstruction (6), suggesting that the effect of the patch design has a more significant impact than the biomechanical properties of the used material. Incorporating an annuloplasty ring during posterior MV reconstruction may help reduce the ballooning effect (20). However, annuloplasty rings have been associated with SIS-ECM failure in some cases (21). An alternative approach involves designing a more restrictive patch with a reduced circumference and height, although this may excessively constrain posterior leaflet motion, thereby increasing the risk of regurgitation. It may also elevate tension between the papillary muscles and annulus, thereby raising the risk of dehiscence or rupture. A third option is to design a patch with perforations in the subvalvular region, allowing physiological blood flow through the centre of the prosthetic cusp (22). The reconstructed MV preserved its native out-of-plane geometry, maintaining physiological cyclic variation in the annular height-to-commissural width ratio, consistent with native valve studies (19,23). The anterior annular segment also retained its characteristic systolic expansion post-repair, in line with previous observations (17,18,23). Following posterior leaflet reconstruction, inter-papillary muscle distance and dynamics remained comparable to those in native valves (24). Additionally, the distance from each papillary muscle tip to its corresponding commissure exceeded the distance to the A2 and P2 scallops, respectively—an anatomical relationship also reported in native studies (24). The posterior papillary muscle to P2 distance was greater than the anterior papillary muscle to A2 distance, further confirming preservation of subvalvular geometry. These findings suggest that the modified patch design maintained functional alignment between the valve leaflets and subvalvular apparatus. This study employed a 2-ply vacuum-pressed SIS-ECM patch, which was found to be pliable and mechanically suitable for posterior MV reconstruction. No tearing or rupture was observed, despite omitting double-folding at anchoring points. While materials with similar biomechanical properties may yield comparable results, the use of alternative materials could influence key outcomes. Further investigation is warranted to evaluate long-term performance, particularly in terms of durability and recellularisation potential. Our findings support the feasibility of using vacuum-pressed SIS-ECM in acute in vivo models. Patch sizing was standardised using magnetic resonance imaging in 80 kg pigs (9); however, clinical translation will require personalised sizing and configuration, accounting for patient-specific anatomy and pathology. The experimental setup described in this study provides a robust platform for evaluating heart valve repair techniques. The porcine model offers strong translational relevance, reflecting anatomical and procedural conditions that are comparable to those in human clinical practice. The controlled environment ensures reproducibility and facilitates a detailed assessment of biomechanical integrity, functional competence, and recellularisation potential—key parameters in evaluating bioscaffold performance. This model supports the systematic development and optimisation of surgical strategies, thereby enhancing the clinical applicability of novel repair approaches. Limitations The posterior MV repair was performed in a healthy porcine model. Thus, no pathophysiological deformities of the left ventricular chamber, left atrium, or the MV itself were observed, which is the case in patients with a diseased MV. Furthermore, the measurements were performed immediately following extensive cardiac surgery. Therefore, the results should not be directly applied to a clinical setting. We did not include a control group undergoing a sham procedure; thus, randomisation or blinding was not applicable in this study. Finally, the setup used in this study does not provide any information on long-term effects, and studies investigating the MV function with a more extended follow-up period are warranted. Conclusions This study demonstrated the feasibility of posterior MV repair using a 2-ply vacuum-pressed SIS-ECM patch in an acute porcine model. The reconstructed MV maintained functionality with preserved haemodynamics and typical subvalvular geometry, and there was no evidence of regurgitation, stenosis, or systolic anterior motion. Annular systolic widening and atrial bending of the reconstructed posterior MV leaflet were observed, potentially affecting stress distribution in the MV. These results suggest that 2-ply vacuum-pressed SIS-ECM is a promising material for MV reconstruction. However, the patch design requires further optimisation, and long-term studies are necessary to test the long-term durability and clinical relevance of the material. Abbreviations MV Mitral valve SD Standard deviation SIS-ECM Small intestinal submucosal extracellular matrix (CorMatrix®) Declarations Authors’ Contributions JHJ, JMH, and MJT conceived the study idea, designed the study, and planned the experimental setup and protocol. JHJ and MJT designed the patch. JHJ, FTA, AEK, and JTV performed the intervention and collected the data. SNS designed software for data collection and analysis. JHJ and AEK analysed and interpreted the results of the study. JHJ wrote the initial draft of the manuscript. All authors discussed the results, reviewed and revised the manuscript, and approved the final version. Availability of Data and Materials The data used in the current study are available from the corresponding author upon reasonable request. Research Involving Human and Animal Rights No human subjects were included in the study. All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees (nr. 2016-15-01201-01132). Funding Statement This work was supported by the Novo Nordisk Foundation [Grant number NNF20OC0065584]. Conflict of Interest Statement The authors declare no conflicts of interest. CorMatrix CardioVascular Inc. provided the small intestinal submucosal extracellular matrix free of charge. The company has not influenced or approved the content of this manuscript. References McNeely, C. & Vassileva, C. 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Mitral valve posterior leaflet reconstruction using extracellular matrix: an acute porcine study†. Eur. J. Cardiothorac. Surg. 54 (5), 832–840 (2018). Mosala Nezhad, Z. et al. Small intestinal submucosa extracellular matrix (CorMatrix®) in cardiovascular surgery: a systematic review. Interact. Cardiovasc. Thorac. Surg. 22 (6), 839–850 (2016). Bruun, V. J., Jensen, L. L., Hasenkam, J. M. & Jedrzejczyk, J. H. Tissue response and clinical outcomes after cardiovascular use of porcine small intestinal small intestinal submucosal extracellular matrix: a systematic review. Front Cardiovasc Med [Internet]. ;Volume 12-2025. Available from: https://www.frontiersin.org/journals/cardiovascular-medicine/articles/ (2025). 10.3389/fcvm.2025.1532157 Jedrzejczyk, J. H. et al. Mechanical and Geometric Characterization of a Novel 2-Ply Vacuum-Pressed Biological Scaffold Patch Design for Posterior Mitral Valve Reconstruction. J. Cardiovasc. Transl Res. ; (2024). MacArthur Clark, J. 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Tables Table 1: Echocardiographic results of the mitral valve at baseline and after MV repair in apical 5-chamber view Parameter Baseline After Repair P-value Annulus diameter (mm) a Systole 28.7 (1.1) 22.4 (1.1) <0.001 Diastole 31.4 (1.0) 24.4 (1.0) <0.001 Distensibility/cyclic change 2.7 (1.8) 2.0 (1.6) 0.334 Systole anterior leaflet part 15.1 (0.7) 12.6 (0.8) <0.001 Systole posterior leaflet part 13.6 (1.0) 9.9 (1.6) <0.001 Tenting Area Total 122.7 (3.9) 99.7 (4.5) <0.001 Anterior leaflet 83.3 (5.1) 70.3 (6.5) <0.001 Posterior leaflet 39.4 (1.7) 29.4 (3.3) <0.001 Tenting height (mm) 7.3 (0.8) 8.6 (1.0) <0.001 Coaptation length (mm) 6.6 (0.5) 9.4 (1.5) <0.001 Leaflet length in diastole (mm) Anterior leaflet 24.1 (0.7) 24.3 (4.3) 0.930 Posterior leaflet 17.9 (0.7) 20.7 (1.1) <0.001 Billowing height (mm) Anterior leaflet 7.7 (0.5) 7.1 (1.3) 0.280 Posterior leaflet 4.4 (0.5) 3.4 (0.5) 0.004 All measurements were obtained in an apical 5-chamber view. Data presented as mean (standard deviation). a Measured in septal-lateral direction. Additional Declarations No competing interests reported. Supplementary Files Graphicalabstract.pdf displays echocardiographic images of the reconstructed MV, with geometric parameters summarised in Table 1. Echocardiography confirmed a fully functional MV in all subjects, with no evidence of regurgitation, stenosis or systolic anterior motion following reconstruction. Posterior leaflet repair led to a statistically significant reduction in septal-lateral annular diameter and a statistically significant increase in posterior leaflet length at end-diastole, while anterior leaflet length remained unchanged. Posterior billowing height was statistically significantly reduced, with no corresponding change in the anterior leaflet. Coaptation length and tenting height were both statistically significantly increased after reconstruction. Cite Share Download PDF Status: Published Journal Publication published 14 Jan, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 19 Nov, 2025 Reviews received at journal 17 Nov, 2025 Reviewers agreed at journal 11 Nov, 2025 Reviews received at journal 02 Nov, 2025 Reviewers agreed at journal 26 Oct, 2025 Reviewers invited by journal 15 Oct, 2025 Editor assigned by journal 14 Oct, 2025 Editor invited by journal 08 Oct, 2025 Submission checks completed at journal 07 Oct, 2025 First submitted to journal 07 Oct, 2025 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-7766713","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":536309711,"identity":"3fa24f48-d407-4d24-83f8-6b5850c59537","order_by":0,"name":"Johannes H. Jedrzejczyk","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYBACxgYeBgMGNhsGPmaowAwitaQxsBGthYGBB4jZDjOwwcwgqIW5vfdAwYey8/Js7LwHGH62McjObCDksJ5zCYYzzt02bGPmS2DsbWMwnk3IFsYZOQbGvG23E9iYeQwYeNsYEucRpeVv2zmwFsa/RGthbDsA1sIMsoWww3rOGBj2nEsG+oXH4LDMOQljgt43bO8xM/hRZifPz3/G8OGbMhvZGQcIaWlgYDOAcYCKJQg5i4FBHhg1DwgrGwWjYBSMghENAAdpN+HfQaH6AAAAAElFTkSuQmCC","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Johannes","middleName":"H.","lastName":"Jedrzejczyk","suffix":""},{"id":536309712,"identity":"748e5f13-6ed6-4a37-9b83-b7c34afbcbdf","order_by":1,"name":"Frederik T. Andersen","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Frederik","middleName":"T.","lastName":"Andersen","suffix":""},{"id":536309713,"identity":"7481796a-401a-475b-8d29-4ad4bbe28b6d","order_by":2,"name":"Alexander Emil Kaspersen","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Alexander","middleName":"Emil","lastName":"Kaspersen","suffix":""},{"id":536309714,"identity":"a668a143-74b3-46b3-a8cd-cb63535667c5","order_by":3,"name":"Jens T. Vaesel","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jens","middleName":"T.","lastName":"Vaesel","suffix":""},{"id":536309715,"identity":"1895892b-aa35-410b-84fd-8777418c46bd","order_by":4,"name":"Dennis O. Ammitzskov","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dennis","middleName":"O.","lastName":"Ammitzskov","suffix":""},{"id":536309716,"identity":"af30bb80-f09b-4525-86c4-bec72124e12d","order_by":5,"name":"Søren N. Skov","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Søren","middleName":"N.","lastName":"Skov","suffix":""},{"id":536309717,"identity":"6c963528-f508-4951-9b8f-4e7c6dcc8562","order_by":6,"name":"J. Michael Hasenkam","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"J.","middleName":"Michael","lastName":"Hasenkam","suffix":""},{"id":536309718,"identity":"0c1db767-2ea1-4159-a6ef-dcc0a115fce3","order_by":7,"name":"Marcell J. Tjørnild","email":"","orcid":"","institution":"Odense University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Marcell","middleName":"J.","lastName":"Tjørnild","suffix":""}],"badges":[],"createdAt":"2025-10-02 13:08:50","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7766713/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7766713/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-026-36236-4","type":"published","date":"2026-01-14T16:30:32+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":94700292,"identity":"de5e5170-30f3-427e-9858-490b294d3363","added_by":"auto","created_at":"2025-10-29 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19:32:21","extension":"xml","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":78573,"visible":true,"origin":"","legend":"","description":"","filename":"0bed640468d3426f944ebd26a8f072e51structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7766713/v1/a41352693d6b589588551a80.xml"},{"id":94700301,"identity":"88197f45-965d-4bbd-b71f-b2bc046ecc88","added_by":"auto","created_at":"2025-10-29 19:32:21","extension":"html","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":89285,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7766713/v1/a3ca660067d249f1f2c61b62.html"},{"id":94700289,"identity":"f9de402b-360b-4232-b0b6-cd5a767748b3","added_by":"auto","created_at":"2025-10-29 19:32:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":143468,"visible":true,"origin":"","legend":"\u003cp\u003ePosterior mitral valve leaflet patch design and surgical technique showing a) geometric template divided into P1-P3 segments (total annular width: 90 mm). b) Overlay on the native valve showing alignment with the anterior and commissural leaflets and orientation towards the papillary muscles. c) the MV in systole, d) annular anchoring of the posterior MV patch, e) the reconstructed MV in diastole, and f) the reconstructed MV in systole.\u003c/p\u003e","description":"","filename":"Figure1191.png","url":"https://assets-eu.researchsquare.com/files/rs-7766713/v1/629bcd97466c4122335949e2.png"},{"id":94700286,"identity":"fc5d797d-4f15-4716-b83e-f0a146e69d22","added_by":"auto","created_at":"2025-10-29 19:32:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":73271,"visible":true,"origin":"","legend":"\u003cp\u003eAnatomical placement of sonomicrometry crystals after posterior mitral valve reconstruction.\u003cstrong\u003e \u003c/strong\u003eEight sonomicrometry crystals (1-8) are positioned along the mitral annulus to capture dynamic annular geometry. Two additional crystals (9 and 10) are sutured to the papillary muscles, allowing quantification of subvalvular motion. Crystal 11 is placed at the left ventricular apex for synchronisation and spatial reference.\u003c/p\u003e","description":"","filename":"Figure1192.png","url":"https://assets-eu.researchsquare.com/files/rs-7766713/v1/5b2eb89062d367068339fa27.png"},{"id":94728338,"identity":"b3effe11-eb0f-4afa-84a6-b89ceb072b74","added_by":"auto","created_at":"2025-10-30 07:03:35","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1036680,"visible":true,"origin":"","legend":"\u003cp\u003eEchocardiographic images of a) the native mitral valve (MV) in systole, b) the reconstructed MV in systole, c) the native MV in diastole, and d) the reconstructed MV in diastole. The white arrows suggest an atrial bending of the posterior MV leaflet in systole.\u003c/p\u003e","description":"","filename":"Figure1193.png","url":"https://assets-eu.researchsquare.com/files/rs-7766713/v1/30755f61c97d0ff1f65c37c1.png"},{"id":94700287,"identity":"355a3348-a0c5-408d-abba-a294ea4920d5","added_by":"auto","created_at":"2025-10-29 19:32:21","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":62160,"visible":true,"origin":"","legend":"\u003cp\u003eIn-plane sonomicrometric measurements after posterior mitral valve repair.\u003cstrong\u003e \u003c/strong\u003eAll error bars indicate standard deviation (SD). a, c) Maximal, minimal, and Δ-values with SD for mitral annular area (MAA), mitral annular circumference (MAC), septal-lateral (SL) distance, and commissure-commissure (CC) distance. b, d) Mean (SD) for the same parameters at four time points: end-diastole (ED), mid-diastole (MD), mid-systole (MS), and end-systole (ES).\u003c/p\u003e","description":"","filename":"Figure1194.png","url":"https://assets-eu.researchsquare.com/files/rs-7766713/v1/866193a286664383e8dd3789.png"},{"id":94700290,"identity":"5ce4e60d-286e-47d7-8cde-62b1149b248a","added_by":"auto","created_at":"2025-10-29 19:32:21","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":67351,"visible":true,"origin":"","legend":"\u003cp\u003eIn-plane sonomicrometric measurements after posterior mitral valve repair.\u003cstrong\u003e \u003c/strong\u003eAll error bars indicate standard deviation (SD). a, c) Maximal, minimal, and Δ-values with SD for mitral annular area (MAA), mitral annular circumference (MAC), septal-lateral (SL) distance, and commissure-commissure (CC) distance. b, d) Mean (SD) for the same parameters at four time points: end-diastole (ED), mid-diastole (MD), mid-systole (MS), and end-systole (ES).\u003c/p\u003e","description":"","filename":"Figure1195.png","url":"https://assets-eu.researchsquare.com/files/rs-7766713/v1/e304f07d6b72227ee315c761.png"},{"id":94729503,"identity":"f9092c5a-d0a1-48b1-83e0-6e8d337304cc","added_by":"auto","created_at":"2025-10-30 07:05:03","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":230088,"visible":true,"origin":"","legend":"\u003cp\u003eAnnular dynamics post-reconstruction (PLR).\u003cstrong\u003e \u003c/strong\u003eCircumferential changes from end-diastole (ED) to end-systole (ES), with a colour scale: blue indicates systolic expansion, red indicates compression.\u003c/p\u003e","description":"","filename":"Figure1196.png","url":"https://assets-eu.researchsquare.com/files/rs-7766713/v1/254e69a6b2165944db2e55a5.png"},{"id":100614818,"identity":"11a978e2-8d6d-404c-a5ea-776317c35d0d","added_by":"auto","created_at":"2026-01-19 17:26:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2424540,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7766713/v1/8e09af4c-4d65-448f-8a6f-acb2214c2fe4.pdf"},{"id":94700291,"identity":"10270b5c-8117-4fc8-a722-5512e7d43252","added_by":"auto","created_at":"2025-10-29 19:32:21","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":184075,"visible":true,"origin":"","legend":"displays echocardiographic images of the reconstructed MV, with geometric parameters summarised in Table\u0026nbsp;1. Echocardiography confirmed a fully functional MV in all subjects, with no evidence of regurgitation, stenosis or systolic anterior motion following reconstruction. Posterior leaflet repair led to a statistically significant reduction in septal-lateral annular diameter and a statistically significant increase in posterior leaflet length at end-diastole, while anterior leaflet length remained unchanged. Posterior billowing height was statistically significantly reduced, with no corresponding change in the anterior leaflet. Coaptation length and tenting height were both statistically significantly increased after reconstruction.","description":"","filename":"Graphicalabstract.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7766713/v1/fcf328c0f9745bf031cf0454.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Functional Competency of a Novel 2-Ply Vacuum-Pressed Biological Scaffold for Posterior Mitral Valve Repair","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSurgical intervention is recommended for patients with severe mitral valve (MV) regurgitation, particularly when conservative treatment is insufficient. MV repair has become more common over the past five decades and is favoured over replacement due to better long-term clinical outcomes (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). However, a successful repair requires sufficient pliable MV tissue (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), often unavailable in patients with rheumatic valve disease, degenerative MV disease, or extensive calcification, necessitating patch repair for adequate reconstruction (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAn effective MV patch material must meet several criteria, including being non-infectious, non-thrombogenic, and non-immunogenic, as well as being pliable and calcification-resistant, while supporting cell growth (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Small intestinal submucosal extracellular matrix (SIS-ECM) has emerged as a promising material for MV patches due to its biocompatibility and mechanical properties, which align well with these requirements.\u003c/p\u003e\u003cp\u003eIn prior studies, our group successfully reconstructed the posterior MV leaflet and chordae tendineae in an acute porcine model using 2-ply lyophilised SIS-ECM (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). However, the material lacked sufficient suture retention strength, necessitating double folding at the anchoring points (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), which could interfere with the degeneration and remodelling process of the bioscaffold. Additionally, clinical studies suggest that lyophilised SIS-ECM may lack durability, with patch failure and recurrent MV regurgitation observed in some instances (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe vacuum-pressing method differs from lyophilisation. In a previous study, we found that vacuum-pressed SIS-ECM exhibits greater mechanical strength than the lyophilised version and is feasible for posterior MV reconstruction in vitro (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). We hypothesise that 2-ply vacuum-pressed SIS-ECM possesses the properties needed for an ideal MV patch material, potentially allowing for posterior MV leaflet and chordae tendineae reconstruction in vivo. Thus, the present study aimed to evaluate our novel patch design for posterior MV and subvalvular reconstruction using 2-ply vacuum-pressed SIS-ECM in an acute porcine model.\u003c/p\u003e"},{"header":"Materials \u0026 Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis experimental in vivo study was conducted at the Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. Each pig served as its own control, with preoperative baseline and post-interventional measurements, eliminating the need for a separate control group. This design reduced the number of animals used by 50%, adhering to the 3 R\u0026rsquo;s principle of replacement, reduction, and refinement (10).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study complied with the National Guidelines for Experimental Animal Research and was approved by the Danish Inspectorate of Animal Experimentation (No. 2016-15-0201-01132).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eReporting was done in accordance with the ARRIVE guidelines.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnimals\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeven female 80-kg pigs (mixed Duroc and Danish Landrace-Yorkshire), sourced from Aarhus University, Aarhus, Denmark, were used. The animal model has been previously described in detail (11).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatch Material\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe posterior MV patch was fashioned from a 100 x 70 mm sheet of 2-ply vacuum-pressed SIS-ECM (CorMatrix\u0026reg;, Cardiovascular Inc., Alpharetta, GA, USA), illustrated in Fig. 1a-b. The vacuum-pressed SIS-ECM material and the patch design have been described in an earlier study (9).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstrumentation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInvasive pressure measurements were obtained using Mikro-Tip pressure catheters (SPR-350S, Millar Instruments, Houston, TX, USA). Baseline and post-interventional MV geometry and leaflet mobility were assessed with epicardial echocardiography (Vivid E9, GE Vingmed Ultrasound AS., Horten, Norway). Eleven piezoelectric 2 mm sonomicrometry crystals (Sonometrics Corp., London, Canada) were used to assess the annular and subvalvular geometry (12).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurgical Procedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTransportation, handling, and anaesthesia have been previously described (11,13). Anaesthesia was maintained by continuous intravenous administration of Propofol (4.375 mg/kg/h), Fentanyl (6\u0026micro;g/kg/h), and Rocuronium (3.125 mg/kg/h). The heart was exposed through a median sternotomy, and the pig was heparinised with 50.000 IU of heparin. Baseline measurements, including epicardial echocardiography and intracardiac and intra-arterial pressure measurements, were performed before the establishment of cardiopulmonary bypass and cardiac arrest by cold blood cardioplegia.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe MV was exposed via a left atriotomy. Four 5-0 Optilene\u0026reg; sutures (B. Braun, Melsungen, Germany) were placed in the annulus at the anterolateral commissure, the P1-P2 indentation, the P2-P3 indentation, and the posteromedial commissure. The posterior MV leaflet was excised at the annular level, and the associated chordae tendineae were transected at the papillary muscle heads. Two additional 5-0 Optilene\u0026reg; sutures were placed in the fibrous portion of each papillary muscle head, oriented anteriorly and posteriorly. The implantation technique is illustrated in Fig. 1c-f.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe P1 and P3 segments of the patch each contained two anchoring points, connected to the anterolateral and posteromedial papillary muscles, respectively. The anchoring points within each segment were spaced 1 cm apart and secured to the papillary muscle heads using three continuous suture loops spanning 2-3 mm, before the patch was parachuted into place. The oversized patch was evenly distributed across the four annular landmark sutures and fixed using a running interlocking suture. It was then attached to the anterior leaflet with a plicated suture at each commissure. No prosthetic ring was implanted. The left atrium was closed with a 4-0 Optilene\u0026reg; running suture, after which the animal was weaned from cardiopulmonary bypass and re-perfused. Off-pump interventional echocardiography, intracardiac, and intra-arterial pressure recordings were performed under spontaneous cardiac activity.\u003c/p\u003e\n\u003cp\u003eCardiopulmonary bypass and cardioplegic arrest were reinitiated, and the left atrium was reopened to place eight annular and three ventricular sonomicrometry crystals (Fig. 2). Annular wires were exteriorised through the atrial wall, and ventricular wires through the apex. Following atrial closure, the animal was weaned from bypass, re-perfused, and sonomicrometry measurements were recorded. Euthanasia was performed under continued anaesthesia via an intravenous overdose of pentobarbital. All procedures were performed by the same surgeon (JHJ) under identical conditions over three weeks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Acquisition \u0026amp; Data Analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSignal acquisition, synchronisation, and analysis of haemodynamic, echocardiographic, and sonometric data were performed according to the same protocol established in our previous study (11). This included processing of pressure waveforms, quantification of leaflet motion, and measurements of annular geometry.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFollowing the assessment of normality, results are presented as mean with standard deviation (SD). Normality was assessed by inspecting quantile plots and tested using the Shapiro-Wilk test. Pressure data were analysed using a mixed-effects model with group (baseline, intervention) as a fixed effect and pig as a random effect. Echocardiographic and hemodynamic parameters obtained from echocardiography were compared using another mixed-effects model with group as a fixed effect and pig as a random effect. Models were fitted using restricted maximum likelihood, and the Kenward-Roger correction method was applied to reduce small-sample bias (14). The homoscedasticity of residuals was checked by plotting them as a function of predicted values. The normality of residuals and random effects was checked by inspection of quantile plots of residuals and best linear unbiased predictors, respectively. Post hoc pairwise comparisons of all variables between groups were performed using a\u0026nbsp;2-tailed least-squares means pairwise t-test, with an alpha level of 0.05. The statistical models were developed with the Biostatistical Advisory Service (BIAS), Aarhus University, Aarhus, Denmark. Statistical analyses were performed using SAS\u003csup\u003e\u0026reg;\u003c/sup\u003e Enterprise Guide\u003csup\u003e\u0026reg;\u003c/sup\u003e software, version 7.1 (SAS, Institute Inc., Cary, NC, USA).\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAll reconstructed valves showed preserved haemodynamic function and geometric properties in all subjects.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHaemodynamic Results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMean peak left atrial pressure (SD) at baseline and after repair showed no statistically significant difference: 9.9 (1.1) vs 9.9 (1.0) mmHg, p = 0.676, diff = 0.002 mmHg, 95% CI: [-1.06;1.05]. The mean MV pressure difference (SD) decreased slightly from 4.5 (2.3) vs 4.1 (2.3) mmHg, p = 0.063, diff = -0.40, 95% CI: [-2,73;1.93]. These findings indicate no evidence of mitral regurgitation or stenosis. The mean ejection fraction (SD) showed no statistically significant difference before and after reconstruction: 56.6 (12.3) vs. 63.7 (1.3) %, p = 0.152, diff = 7.10, 95% CI: [-1.75; 15.95]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEchocardiographic Results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFig. 3 displays echocardiographic images of the reconstructed MV, with geometric parameters summarised in Table 1. Echocardiography confirmed a fully functional MV in all subjects, with no evidence of regurgitation, stenosis or systolic anterior motion following reconstruction. Posterior leaflet repair led to a statistically significant reduction in septal-lateral annular diameter and a statistically significant increase in posterior leaflet length at end-diastole, while anterior leaflet length remained unchanged. Posterior billowing height was statistically significantly reduced, with no corresponding change in the anterior leaflet. Coaptation length and tenting height were both statistically significantly increased after reconstruction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSonomicrometry Results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFig. 4 present in-plane geometric measurements, including annular area, circumference, septal-lateral distance, and commissure-commissure distance. Fig. 5a-d illustrates out-of-plane MV annular geometric results, including annular height, annular height-to-commissural width ratio, annular segmental distance, and the annular crystal distances at end-systole to the least square plane as an expression of the saddle shape of the MV. Subvalvular geometric results shown in Fig. 5d-f include cyclic papillary muscle distances and their respective distance to the annulus. Fig. 6 illustrates annular segmental circumferential changes from end-diastole to end-systole, with a colour scale indicating regional systolic circumferential changes.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePosterior MV leaflet pathology can convert a \u0026ldquo;simple repair\u0026rdquo; to a challenging surgical procedure (2,4), and a total MV replacement may be warranted in cases with extensive damage to the posterior MV leaflet (2). While prior in vitro (15) and animal studies (6) on 2-ply lyophilised SIS-ECM have shown promising results, clinical data have raised concerns about its long-term efficacy and durability (7,8). This acute porcine study examined transvalvular pressure differences, MV annular and subvalvular geometry, as well as valve dynamics before and after reconstruction of the posterior MV leaflet and subvalvular apparatus with 2-ply vacuum-pressed SIS-ECM. The posterior MV and subvalvular apparatus were fully functional, with no regurgitant jets on the colour Doppler echocardiography and no statistically significant change in peak left atrial pressure. Furthermore, no post-reconstruction indication of stenosis was found, as a similar mean pressure difference across the MV was observed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDouble folding the material at the anchoring points was omitted, based on findings from our previous in vitro study of 2-ply vacuum-pressed SIS-ECM (9). Considering the earlier in vitro findings and the current in vivo findings, the vacuum-pressed SIS-ECM exhibits stronger biomechanical characteristics compared to the lyophilised SIS-ECM, offering several advantages. First, it simplifies the surgical technique by eliminating the need for double folding, potentially reducing operative time. Second, it may reduce the risk of thrombosis, which could arise from the potential space created between double-folding the material. Third, the material preserves its intrinsic properties for degeneration and recellularisation. However, further studies are needed to confirm whether its suture retention strength remains sufficient over time.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEchocardiographic parameters were comparable to those observed in the human heart (16), and post-repair imaging demonstrated an anatomical and functional appearance similar to the native MV. A statistically significant reduction in the septal-lateral annular dimension was observed following repair. Although annular downsizing in this plane may reduce the left ventricular outflow tract area and increase the risk of systolic anterior motion, neither echocardiographic imaging nor catheter-based pressure measurements revealed evidence of this. Despite the reduced septal-lateral diameter, the mitral annulus exhibited similar systolic contraction before and after repair, indicating preserved cyclic annular dynamics.\u003c/p\u003e\n\u003cp\u003eThe billowing height of the native anterior MV leaflet was preserved following reconstruction, whereas the posterior leaflet showed a statistically significant reduction. This reduction was attributed to atrial bending of the reconstructed posterior leaflet, as observed on echocardiography. The deformation likely results from excess tissue and the absence of intermediate and basal chordae, which usually counteract systolic pressure directed toward the left atrium (6). Atrial bending of the posterior leaflet is a known limitation of this surgical technique and may alter left ventricular flow dynamics and stress distribution across the MV apparatus. Further studies are needed to evaluate the long-term biomechanical and functional implications of this phenomenon.\u003c/p\u003e\n\u003cp\u003eChanges in annular area, circumference, and commissure-commissure distance confirmed that the size and dynamic behaviour of the reconstructed MV were generally compatible with those reported in native valve studies (17,18). Both echocardiography and sonomicrometry demonstrated a reduction in the septal-lateral dimension compared with baseline and native valves (17,19). However, during systole, an increase in annular area, circumference, and commissure-commissure distance was observed relative to native measurements, indicating an unphysiological annular widening. This was further supported by segmental analysis, which revealed systolic widening of the posterior annulus and corresponding circumferential deformation. \u0026nbsp;A similar pattern was previously observed in our animal study using lyophilised 2-ply SIS-ECM for posterior leaflet reconstruction\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e(6), suggesting that the effect of the patch design has a more significant impact than the biomechanical properties of the used material.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIncorporating an annuloplasty ring during posterior MV reconstruction may help reduce the ballooning effect (20). However, annuloplasty rings have been associated with SIS-ECM failure in some cases (21). An alternative approach involves designing a more restrictive patch with a reduced circumference and height, although this may excessively constrain posterior leaflet motion, thereby increasing the risk of regurgitation. It may also elevate tension between the papillary muscles and annulus, thereby raising the risk of dehiscence or rupture. A third option is to design a patch with perforations in the subvalvular region, allowing physiological blood flow through the centre of the prosthetic cusp (22).\u003c/p\u003e\n\u003cp\u003eThe reconstructed MV preserved its native out-of-plane geometry, maintaining physiological cyclic variation in the annular height-to-commissural width ratio, consistent with native valve studies (19,23). The anterior annular segment also retained its characteristic systolic expansion post-repair, in line with previous observations (17,18,23). Following posterior leaflet reconstruction, inter-papillary muscle distance and dynamics remained comparable to those in native valves (24). Additionally, the distance from each papillary muscle tip to its corresponding commissure exceeded the distance to the A2 and P2 scallops, respectively\u0026mdash;an anatomical relationship also reported in native studies (24). The posterior papillary muscle to P2 distance was greater than the anterior papillary muscle to A2 distance, further confirming preservation of subvalvular geometry. These findings suggest that the modified patch design maintained functional alignment between the valve leaflets and subvalvular apparatus.\u003c/p\u003e\n\u003cp\u003eThis study employed a 2-ply vacuum-pressed SIS-ECM patch, which was found to be pliable and mechanically suitable for posterior MV reconstruction. No tearing or rupture was observed, despite omitting double-folding at anchoring points. While materials with similar biomechanical properties may yield comparable results, the use of alternative materials could influence key outcomes. Further investigation is warranted to evaluate long-term performance, particularly in terms of durability and recellularisation potential. Our findings support the feasibility of using vacuum-pressed SIS-ECM in acute in vivo models. Patch sizing was standardised using magnetic resonance imaging in 80 kg pigs (9); however, clinical translation will require personalised sizing and configuration, accounting for patient-specific anatomy and pathology.\u003c/p\u003e\n\u003cp\u003eThe experimental setup described in this study provides a robust platform for evaluating heart valve repair techniques. The porcine model offers strong translational relevance, reflecting anatomical and procedural conditions that are comparable to those in human clinical practice. The controlled environment ensures reproducibility and facilitates a detailed assessment of biomechanical integrity, functional competence, and recellularisation potential\u0026mdash;key parameters in evaluating bioscaffold performance. This model supports the systematic development and optimisation of surgical strategies, thereby enhancing the clinical applicability of novel repair approaches.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe posterior MV repair was performed in a healthy porcine model. Thus, no pathophysiological deformities of the left ventricular chamber, left atrium, or the MV itself were observed, which is the case in patients with a diseased MV. Furthermore, the measurements were performed immediately following extensive cardiac surgery. Therefore, the results should not be directly applied to a clinical setting. We did not include a control group undergoing a sham procedure; thus, randomisation or blinding was not applicable in this study. Finally, the setup used in this study does not provide any information on long-term effects, and studies investigating the MV function with a more extended follow-up period are warranted.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study demonstrated the feasibility of posterior MV repair using a 2-ply vacuum-pressed SIS-ECM patch in an acute porcine model. The reconstructed MV maintained functionality with preserved haemodynamics and typical subvalvular geometry, and there was no evidence of regurgitation, stenosis, or systolic anterior motion. Annular systolic widening and atrial bending of the reconstructed posterior MV leaflet were observed, potentially affecting stress distribution in the MV. These results suggest that 2-ply vacuum-pressed SIS-ECM is a promising material for MV reconstruction. However, the patch design requires further optimisation, and long-term studies are necessary to test the long-term durability and clinical relevance of the material.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMitral valve\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eStandard deviation\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSIS-ECM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSmall intestinal submucosal extracellular matrix (CorMatrix\u0026reg;)\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJHJ, JMH, and MJT conceived the study idea, designed the study, and planned the experimental setup and protocol. JHJ and MJT designed the patch. JHJ, FTA, AEK, and JTV performed the intervention and collected the data. SNS designed software for data collection and analysis. JHJ and AEK analysed and interpreted the results of the study. JHJ wrote the initial draft of the manuscript. All authors discussed the results, reviewed and revised the manuscript, and approved the final version.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used in the current study are available from the corresponding author upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResearch Involving Human and Animal Rights\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo human subjects were included in the study. All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees (nr. 2016-15-01201-01132).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Novo Nordisk Foundation [Grant number NNF20OC0065584].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest. CorMatrix CardioVascular Inc. provided the small intestinal submucosal extracellular matrix free of charge. The company has not influenced or approved the content of this manuscript. \u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMcNeely, C. \u0026amp; Vassileva, C. 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Annular Dynamics and Leaflet Geometry in Patch Reconstruction of the Posterior Mitral Leaflet After Adding a Flexible Annuloplasty Ring. \u003cem\u003eCardiovasc. Eng. Technol.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e (6), 748\u0026ndash;759 (2020).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArbona, M. A., David, T. E., David, C. M. \u0026amp; Rao, V. Results of mitral valve reconstruction using substitute extracellular matrix. \u003cem\u003eJTCVS Tech.\u003c/em\u003e \u003cb\u003e16\u003c/b\u003e, 43\u0026ndash;48 (2022).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSzałański, P., Uziębło-Życzkowska, B. \u0026amp; Zaleska, M. Combined total mitral and tricuspid valve reconstruction with the use of CorMatrix in an adult. \u003cem\u003eInteract. Cardiovasc. Thorac. Surg.\u003c/em\u003e \u003cb\u003e28\u003c/b\u003e (1), 158\u0026ndash;160 (2019).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSkov, S. N. et al. Remodeling Mitral Annuloplasty Ring Concept with Preserved Dynamics of Annular Height. \u003cem\u003eJ. Heart Valve Dis.\u003c/em\u003e \u003cb\u003e26\u003c/b\u003e (3), 295\u0026ndash;303 (2017).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJensen, H. et al. Three-dimensional assessment of papillary muscle displacement in a porcine model of ischemic mitral regurgitation. \u003cem\u003eJ. Thorac. Cardiovasc. Surg.\u003c/em\u003e \u003cb\u003e140\u003c/b\u003e (6), 1312\u0026ndash;1318 (2010).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: Echocardiographic results of the mitral valve at baseline and after MV repair in apical 5-chamber view\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter Repair\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003eAnnulus diameter (mm)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Systole\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e28.7 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e22.4 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Diastole\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e31.4 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e24.4 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Distensibility/cyclic change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e2.7 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e2.0 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.334\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Systole anterior leaflet part\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e15.1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12.6 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Systole posterior leaflet part\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e13.6 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e9.9 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003eTenting Area\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Total\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e122.7 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e99.7 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Anterior leaflet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e83.3 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e70.3 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Posterior leaflet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e39.4 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e29.4 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003eTenting height (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e7.3 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e8.6 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003eCoaptation length (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e6.6 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e9.4 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003eLeaflet length in diastole (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Anterior leaflet\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e24.1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e24.3 (4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.930\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Posterior leaflet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e17.9 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e20.7 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003eBillowing height (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Anterior leaflet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e7.7 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7.1 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.280\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Posterior leaflet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e4.4 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e3.4 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 624px;\"\u003e\n \u003cp\u003eAll measurements were obtained in an apical 5-chamber view. Data presented as mean (standard deviation). \u003csup\u003ea\u003c/sup\u003eMeasured in septal-lateral direction.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Mitral valve, mitral valve repair, patch repair, bioscaffold, small intestinal submucosal extracellular matrix.","lastPublishedDoi":"10.21203/rs.3.rs-7766713/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7766713/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThis study assessed the feasibility of posterior mitral valve leaflet and subvalvular reconstruction in an acute porcine model using a novel 2-ply vacuum-pressed small intestinal submucosal extracellular matrix (SIS-ECM) patch.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eReconstruction was performed in an acute 80-kg porcine model (n\u0026thinsp;=\u0026thinsp;7), using a novel 2-ply vacuum-pressed SIS-ECM (CorMatrix\u0026reg;) patch for posterior mitral reconstruction. Echocardiography and left ventricular pressure were assessed pre- and post-interventional. Sonomicrometry was used to evaluate the geometry and valve dynamics.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe reconstructed mitral valves were all fully competent. The peak left atrial pressure at baseline and post-reconstruction was 9.9 (1.1) vs 9.9 (1.0) mmHg, p\u0026thinsp;=\u0026thinsp;0.676, diff\u0026thinsp;=\u0026thinsp;0.002 mmHg, 95% CI: [-1.06;1.05], and the mean trans-mitral pressure difference was 4.5 (2.3) vs 4.1 (2.3) mmHg, p\u0026thinsp;=\u0026thinsp;0.063, diff = -0.40, 95% CI: [-2,73;1.93] The out-of-plane characteristics and subvalvular geometry of the mitral valve were preserved after reconstruction. Slight atrial bending of the reconstructed posterior leaflet and systolic annular ballooning were observed.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eIn an acute porcine model, we successfully reconstructed the posterior mitral valve and subvalvular apparatus using our modified 2-ply vacuum-pressed SIS-ECM patch. The bioscaffold demonstrated short-term durability in vivo, warranting further investigation of its long-term durability.\u003c/p\u003e","manuscriptTitle":"Functional Competency of a Novel 2-Ply Vacuum-Pressed Biological Scaffold for Posterior Mitral Valve Repair","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-29 19:32:16","doi":"10.21203/rs.3.rs-7766713/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-20T03:46:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-18T00:38:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"110626632689207950989202690358906037596","date":"2025-11-12T00:06:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-02T20:03:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"36859321603596449010581851558928163311","date":"2025-10-26T19:27:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-15T15:22:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-14T20:22:23+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-08T12:22:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-07T09:28:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-10-07T09:16:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"59eafbe7-dc7e-4217-b540-648e88b747c4","owner":[],"postedDate":"October 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":57016759,"name":"Health sciences/Cardiology"},{"id":57016760,"name":"Health sciences/Diseases"},{"id":57016761,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-01-19T16:48:59+00:00","versionOfRecord":{"articleIdentity":"rs-7766713","link":"https://doi.org/10.1038/s41598-026-36236-4","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-01-14 16:30:32","publishedOnDateReadable":"January 14th, 2026"},"versionCreatedAt":"2025-10-29 19:32:16","video":"","vorDoi":"10.1038/s41598-026-36236-4","vorDoiUrl":"https://doi.org/10.1038/s41598-026-36236-4","workflowStages":[]},"version":"v1","identity":"rs-7766713","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7766713","identity":"rs-7766713","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}