Microneedle, a one-plane bevel-tipped fabrication by 3D printing process.

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Isabella Villota, Paulo C. Calvo, Oscar I. Campo, Faruk Fonthal Rico This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1490579/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 This article presents the microneedles analysis where the design parameters studied were length, inner and outer diameter range. The ANSYS software was used to analyze the mechanical behavior of the microneedles. Following this, the range of inner and outer diameters were completed by mechanical simulations, getting from 30 μm to 134 μm, as the inner diameter range and 208 μm to 250 μm as the outer diameter range. With these ranges, a mathematical model was made using fourth-order polynomial regression, with a correlation of 0,9993. This mathematical model generalizes the relationship of the inner diameter to the outer diameter within the ranges, ensuring a safety factor of four, where Von Misses forces of the microneedle are around 17.931 MPa. In addition, the microneedle concept was made by 3D printing using a biocompatible resin of class 1. The features presented by the microneedle designed in this work make it a promising option to be implemented in a transdermal drug delivery device. Microneedles Transdermal drug delivery finite element analysis 3D printing Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 1. Introduction Transdermal drug delivery (TDD) is administering minimally invasive drugs through different skin layers, resulting in painless and comfortable drug administration [ 1 , 2 ]. This method is becoming increasingly appealing and desirable for drug delivery because of its advantages compared to conventional methods of drug delivery [ 1 – 5 ]. Despite being a great drug delivery alternative, TDD faces some challenges, one of the most important of which is that not all drugs can pass through the skin with the necessary characteristics for therapeutic actions [ 6 ]. Nowadays, methods are being used to improve transdermal delivery of insulin and other drugs using new micro-and nanotechnologies [ 7 – 9 ] that help overcome the challenges of TDD. On the other hand, there are different devices for TDD, such as the transdermal patch composed of microneedles (MN). Several researchers have studied MNs as a tool for transdermal drug delivery. These MN have sizes that are in the order of microns, mostly with lengths of 150 µm up to 1500 µm, this being sufficient to release the drug into the epidermis, width between 50 µm and 250 µm [ 6 ]. Drug delivery using microneedle devices has shown good permeability and efficacy [ 10 ]. There are different techniques to manufacture MNs, especially microelectromechanical systems technologies [ 11 ], most of which require tools with high costs. As a result, various researchers have used alternative methods that are less costly and sometimes easier to implement. One of these methods is additive manufacturing (3D printing) which has revolutionized pharmaceutical and biomedical sciences due to the manufacturing speed and cost-effective prototypes [ 12 ]. In the last years, several researchers have obtained promising results in studies that have been used for MN printing [ 13 – 15 ], which shows a long way to go in this method. 3D printing makes it possible to use different materials. In addition, other authors who used this method to produce MNs used biocompatible resins [ 15 – 17 ]. This paper presents the proposed designs of two different shapes of MNs based on the tip structure of 1- and 3-bevel hypodermic needles, with a relatively simple form that can facilitate their implementation in 3D printing with class 1 biocompatible resin that has high mechanical strength and puncture capacity. Finite element analysis (FEA) makes it possible to observe and validate the mechanical behavior in the presence of the loads applied to each MN structure. A mathematical model is also obtained that relates the inner and outer diameter of the MN within established ranges of these design parameters. 3D printing of the two designs was also implemented in the Form2-Formlabs printer to observe which of these designs achieves the best print resolutions. 2. Theoretical Analysis 2.1. Structural Design The structural design of MNs is based on creating a one-plane bevel-tipped needle and three bevel-tip. These structures are relatively simple and allow an adequate load distribution on the network, avoiding structural damage during the MN insertion process. The basic shape of the MNs is a cylinder with a length of 450 µm. The inner and outer diameter ranges are established to use any value within them because the dimensions for the manufacture of MNs greatly depend on the available resources. The ranges maintain the values of inner and outer diameters without exceeding the sizes of an MN, without affecting the mechanical behavior of the MN, and with a good safety factor for future use in the medical area. In the inner diameter range, a minimum of 30 µm is established and a maximum of 250 µm for the outer diameter. If this value is outstripped, it would be outside the accepted dimensions for an MN [ 6 ]. Mechanical simulations establish that this diameter range ensures that the MN can overcome the force necessary to pierce the skin without presenting mechanical failures and provide a safety factor of 4. Values similar and close to this inner diameter range have been used in medical device designs, such as needles, that prove suitable for use [ 18 , 19 ]. For the manufacture of MNs, the printing quality will determine the diameter values used to obtain a good structure with good printing resolutions. 2.1.1. Microneedle with the tip in the form of a one-plane bevel-tipped needle (MNTB1). The structure of this MN has a tip forming an angle ( θ ) of 45° between the lateral surface and the beveled plane, a length of 450 µm and a range of inner diameter ( β ) and outer diameter ( α ). A single-plane beveled hypodermic needle inspires the shape of this tip, the tip of which acts as a cutting edge, see Fig. 1 . This MN is characterized by generating a force asymmetrically, causing the tissue cut to occur at a compensating angle depending on the bevel angle, needle flexibility, and tissue properties [ 20 ]. 2.1.2. Microneedle with the tip in the form of 3 bevel-tip (MNTB3). The MN structure of the tip is inspired by a hypodermic needle three bevel tip, i.e., it has three areas, where the force exerted by the skin will be distributed during penetration has two shear angles, θ 1 = 30° and θ 2 = 35° as shown in Fig. 2 , a length of 450 µm and a range of inner diameter ( β ) and outer diameter ( α ). The shape of the tip that formed by the uppercuts (bevel 2 and 3) makes this MN have a sharper tip, a fundamental characteristic of the performance of the needle insertion because the contact area between the MN is mainly concentrated in the part of the pointed tip at the time of the initial cut [ 21 ]. 2.2. Theoretical microneedle Mechanical Analysis The stratum corneum is the principal cutaneous layer that mainly influences the viscoelastic property of the skin; this property is responsible for generating resistance when the skin is perforated, providing the maximum insertion resistance of an MN [ 22 ], causing compression on the MN structure. It is necessary to overcome the skin's opposition for the MN to penetrate the skin. The evaluation of MN mechanical stresses is carried out simulating the forces to which it's subjected just at the moment of insertion; this is the case where the MN is exposed to maximum resistance by the skin. The axial force that the microneedle can withstand without producing irreversible negative effects on its structure is provided with the compressive or yield stress ( σy ); this stress is comprised by Eq. (1) that relates the cross-section ( A ) of the analyzed section with the force that the MN can withstand without breaking ( F compressive ). \({\sigma }_{y}=\frac{{F}_{compressive}}{A}\) , (1) It is necessary to know the values of some mechanical properties of the material to be worked with to study the forces on the MN, which is class 1 biocompatible resin. These material properties are tensile strength of 73 MPa and a young's modulus of 2,9 GPa since the values obtained in the results depend directly on these properties. In addition, the F compressive used was 0,5 N because this value is adequate to simulate the force needed to pierce the skin in a hydration condition because it is within ranges established in other works [ 23 , 24 ]. 3. Finite Element Analysis (Fea) The main reason for the mechanical analysis of MNs is to determine the behavior of the structure, and the material is chosen since they must be able to correctly support the skin's resistance without generating adverse effects such as buckling of the MN structure during the insertion process. A fundamental factor that decreases the probability of buckling is to have an adequate wall thickness. The simulations of the two-needle designs performed with the biocompatible resin class 1, with the mechanical properties mentioned above and a Poisson coefficient of 0,35 established by resins with similar characteristics was used [25, 26]. The results obtained with these simulations show that MN design presents lower Von Misses stresses and deformations [23]. Other results are the values of the available ranges of inner and outer diameter with the mechanical simulations. With these, a mathematical model is taken that generalizes the relationship of these two design parameters within the ranges obtained, ensuring the mechanical integrity of the MN within these ranges and also allows the MN to have an adequate safety factor for its future medical implementation. 3.1. Initial mechanical analysis of microneedle structures For this mechanical analysis, the two MN designs (MNTB1 and MNTB3) were evaluated under the same conditions, a compression force of 0,5N and specific geometric dimensions: MN length of 450 µm, inner diameter ( β ) of 30 µm and outer diameter ( α ) of 250 µm, values within the initially known ranges. These simulations showed that the MN design with the lowest Von Misses stresses was MNTB1, with a maximum stress of 12.451 MPa see Fig. 3 and a maximum strain of 0,0015442. While the MNTB3 design presented a maximum stress of 15.903 MPa see Fig. 4 and maximum deformation of 0,0013586. 3.2. Generalized outer and inner diameter ranges for design MNTB1 with a factor of safety of 4 The generalized ranges were obtained for the MN design with the lowest Von Misses stresses, MNTB1. With the minimum diameter of 30 µm, the outer diameter varied in the mechanical simulation until finding the value where the Von Misses forces were as close as possible to 18.250 MPa (since this is the permissible value for safety factor 4). Considering that the material's tensile strength is 73 MPa, the minimum outer diameter was found around 208 µm, where a maximum Von Misses stress of 17.818 MPa, see Fig. 5, and with the maximum outer diameter of 250 µm the same procedure was performed. However, varying the inner diameter until finding the maximum value where the MN did not exceed the tensile strength of the resin, being this 134 µm, maximum inner diameter, with a Von Misses stress of 17.931 MPa, see Fig. 6. Table 1 shows the values obtained for the inner and outer diameter. Table 1 Result of inner and outer diameter ranges. Diameter (µm) Min. value Max. value Inner 30 134 Outer 208 250 3.3. A mathematical model for generalizing the outer/inner ratio diameter within the obtained ranges A mathematical model that generalizes the relationship of the diameters within the ranges obtained was developed. One characteristic of the model is flexibility in the microneedle design since any diameter value within the ranges can be used; this can be very useful when manufacturing the microneedle. On many occasions, the available manufacturing resources may limit microneedles' manufacture in micrometer sizes, as specialized technology is required. It also ensures that the MN design has an adequate safety factor for future manufacturing and implementation. First, a graph was made to observe the behavior and trend of the data, for which 12 values were chosen within the inner and outer diameter ranges, see Table 2. This table also shows that none of the values in this range presents stresses higher than the permissible value for a safety factor of 4, confirming that the design parameters preserve the mechanical integrity of the MN in these ranges. Next, using a fourth-degree polynomial regression, which was the one that perfectly fitted the trend of the data (see Fig. 7). Finally, a mathematical model corresponding to the form shown in equation two is obtained for the study. Where A presents a value of 4,9622e-7, B of -1,8167e-4, C of 0,0256, D of -1,1671, and E of 224,3235, values found in MATLAB when doing the polynomial regression, also, a data correlation of 0,9993 was obtained, which indicates that the behavior of the data and the fourth-degree polynomial regression have a very high and good correlation. The inner or outer diameter values found by this mathematical model will allow the design to present a Von Misses stress similar or close to 17.998 MPa, which is the average value of the data obtained in this study. Table 2 Inner and outer diameter values within the established range, and von misses stress values were obtained in each case. Inner diameter (µm) Outer diameter (µm) Von Misses stresses (MPa) 30 208 17.818 40 208 18.043 50 210 18.170 60 214 18.023 70 218 17.976 80 222 17.983 90 226 18.080 100 232 17.860 110 236 18.090 120 242 18.023 130 248 17.979 134 250 17.931 4. Microneedle 3d Printing The 3D printing of the MNs was performed with the Form 2- Formlabs printer and a class 1 biocompatible resin. The cleaning and curing processes of the MNs were performed following the protocols given by the material manufacturer. The MNTB1 design was the one manufactured in 3D printing, where a good printing resolution was observed. It could be seen that the printed format did correspond to the modeled design and that the experimental geometric dimensions were very close to the theoretical ones. Two printouts MNs were fabricated, one with the minimum values and the other with the maximum diameters. Although the impression achieved a physical appearance very similar to the proposed design, there was resin clogging in the inner holes of the MN, both for the impression of minimum and maximum diameter values. Still, for the maximum values, the clogging was lower. See Fig. 8 , observing that a better printing resolution is obtained the larger the dimensions to be printed. 5. Conclusions And Future Outlook This research paper shows useful and relevant information for the design and fabrication of MN, analyzing the mechanical behavior of the structures designed, finding the ranges of inner and outer diameters necessary so that the MN did not have mechanical failures and that these dimensions allowed the 3D printing. A mathematical model was also found to generalize the outer and inner diameter ratios in the obtained ranges. The FEA simulations showed that the MNTB1 design was the one that got the lowest von Misses stresses, and this design was then the one with the best mechanical behavior. Also, the inner and outer diameters range allows the needle to behave mechanically appropriately during insertion. The range is between 30 µm and 134 µm for the inner diameter and 208 µm to 250 µm for the outer diameter. In addition, simulations showed that the design, dimensions, and material support the force exerted by the skin at the time of penetration of the MN, which shows that it can be coupled in a method of transdermal drug delivery. The mathematical model obtained that generalizes the relation between inner and outer diameter allows the design to be universal in manufacturing because there is not a single value of diameters. The model does not fail mechanically and can be printed. The fabrication of the MNTB1 model in 3D printing showed a high resolution of impressive appearance and dimensions very similar to those of the designed model. However, the inner cavity of the MN presented resin clogging, as the MNs are in micrometer orders that make the 3D printing process more rigorous. 3D printing still has many challenges to face and must be studied in depth to perfect this method more and more, especially in very small details such as inner holes. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Author Contributions: Conceptualization, F.F. and I.V., methodology, F.F., P.C. and O.C., software, I.V. and O.C., validation, I.V., O.C. and F.F., formal analysis, F.F., I.V. and O.C., investigation, I.V., O.C. and F.F., resources, O.C. and F.F., data curation, I.V. and P.C, writing—original draft preparation, I.V., writing—review and editing, O.C and F.F., visualization, F.F., supervision, F.F., project administration, O.C. and F.F. All authors have read and agreed to the published version of the manuscript. Data Availability: Not applicable. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent to publish: Not applicable. Conflicts of Interest: The authors declare no conflict of interest. Acknowledgments: Thanks to Universidad Autónoma de Occidente, the institution that supported this research project and the UAO young researcher of I.Villota. Also, to Brandon Quintero for guidance on ANSYS software and simulations. References Xu J, Xu D, Xuan X, He H. 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In: Huntsman, Technical Data Sheet - Araldite® LY 5052/Aradur® 5052. 2012. https://es.scribd.com/document/402041100/Araldite-FT-LY-5052-Aradur-5052-en-1 . Saseendran S, Wysocki M, Varna J. Cure-state dependent viscoelastic Poisson’s ratio of LY5052 epoxy resin. Adv Manuf Polym Compos Sci. 2017. https://10.1080/20550340.2017.1348002 . Supplementary Files Graphicalabstract.png 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. 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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-1490579","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":99710427,"identity":"e2ca691b-4621-46a7-9a1a-0c2e9272094c","order_by":0,"name":"Isabella Villota","email":"","orcid":"","institution":"Universidad Autónoma de Occidente: Universidad Autonoma de Occidente","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Isabella","middleName":"","lastName":"Villota","suffix":""},{"id":99710428,"identity":"bd40b3c9-d9e5-47cf-bf76-87712fa181c7","order_by":1,"name":"Paulo C. 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16:30:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":53539,"visible":true,"origin":"","legend":"\u003cp\u003e\tSchematic illustration of MNTB3 design.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-1490579/v1/419f3f9d37f3faf4f8e79025.png"},{"id":20614197,"identity":"73c186e2-7281-4301-9226-56648e7cde24","added_by":"auto","created_at":"2022-04-21 16:35:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":132451,"visible":true,"origin":"","legend":"\u003cp\u003eVon Misses Stresses MNTB1.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-1490579/v1/61a8e628c474cbca89e4fa95.png"},{"id":20614270,"identity":"ab12a2d2-a75d-4d57-9021-d8ce30682447","added_by":"auto","created_at":"2022-04-21 16:40:30","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":85536,"visible":true,"origin":"","legend":"\u003cp\u003eVon Misses Stresses MNTB3.\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-1490579/v1/ef4b983f665edf55bebbb531.png"},{"id":20613751,"identity":"fbb57acf-5d71-4359-bcfd-7fa73774d86e","added_by":"auto","created_at":"2022-04-21 16:30:30","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":73879,"visible":true,"origin":"","legend":"\u003cp\u003e\tVon Misses stresses of MNTB1, inner diameter of 30 μm.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Fig5.png","url":"https://assets-eu.researchsquare.com/files/rs-1490579/v1/d62c2eb934909bc9a5509424.png"},{"id":20614199,"identity":"2d872f31-324b-4368-be96-0278101af03c","added_by":"auto","created_at":"2022-04-21 16:35:30","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":78972,"visible":true,"origin":"","legend":"\u003cp\u003e\tVon Misses stresses of MNTB1, inner diameter of 134 μm.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Fig6.png","url":"https://assets-eu.researchsquare.com/files/rs-1490579/v1/5d895633298d42505def14bf.png"},{"id":20614271,"identity":"14c4e2c8-6f38-4b65-bc26-1f1da5970a25","added_by":"auto","created_at":"2022-04-21 16:40:30","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":47007,"visible":true,"origin":"","legend":"\u003cp\u003e\tGraph of fourth-degree polynomial relationship: The x-axis is the inner diameter (µm), and the y-axis is the outer diameter (μm).\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Fig7.png","url":"https://assets-eu.researchsquare.com/files/rs-1490579/v1/3d3ef5e84661fd8d092f1463.png"},{"id":20613755,"identity":"bf061abe-fb49-4b33-ba66-49892d05a9d5","added_by":"auto","created_at":"2022-04-21 16:30:30","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":275045,"visible":true,"origin":"","legend":"\u003cp\u003e\tPrinting of the MNTB1 design: (\u003cstrong\u003ea\u003c/strong\u003e) printing with maximum diameter values, (\u003cstrong\u003eb\u003c/strong\u003e) printing with minimum diameter values.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Fig8.png","url":"https://assets-eu.researchsquare.com/files/rs-1490579/v1/f9fd3da469dd50d7d0b26f49.png"},{"id":21375321,"identity":"47927ea3-54df-4b47-ab12-a331820a620a","added_by":"auto","created_at":"2022-05-12 08:22:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1032219,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1490579/v1/3c7eb127-ffeb-4caa-93ee-f4d9bc7ab6f4.pdf"},{"id":20613750,"identity":"df7194a0-8016-4951-b12c-7452af8e43b6","added_by":"auto","created_at":"2022-04-21 16:30:30","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":283352,"visible":true,"origin":"","legend":"","description":"","filename":"Graphicalabstract.png","url":"https://assets-eu.researchsquare.com/files/rs-1490579/v1/8e53ec7d7a51d47867ef28d0.png"}],"financialInterests":"","formattedTitle":"Microneedle, a one-plane bevel-tipped fabrication by 3D printing process.","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eTransdermal drug delivery (TDD) is administering minimally invasive drugs through different skin layers, resulting in painless and comfortable drug administration [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This method is becoming increasingly appealing and desirable for drug delivery because of its advantages compared to conventional methods of drug delivery [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite being a great drug delivery alternative, TDD faces some challenges, one of the most important of which is that not all drugs can pass through the skin with the necessary characteristics for therapeutic actions [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Nowadays, methods are being used to improve transdermal delivery of insulin and other drugs using new micro-and nanotechnologies [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] that help overcome the challenges of TDD.\u003c/p\u003e \u003cp\u003eOn the other hand, there are different devices for TDD, such as the transdermal patch composed of microneedles (MN). Several researchers have studied MNs as a tool for transdermal drug delivery. These MN have sizes that are in the order of microns, mostly with lengths of 150 \u0026micro;m up to 1500 \u0026micro;m, this being sufficient to release the drug into the epidermis, width between 50 \u0026micro;m and 250 \u0026micro;m [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Drug delivery using microneedle devices has shown good permeability and efficacy [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere are different techniques to manufacture MNs, especially microelectromechanical systems technologies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], most of which require tools with high costs. As a result, various researchers have used alternative methods that are less costly and sometimes easier to implement. One of these methods is additive manufacturing (3D printing) which has revolutionized pharmaceutical and biomedical sciences due to the manufacturing speed and cost-effective prototypes [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In the last years, several researchers have obtained promising results in studies that have been used for MN printing [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], which shows a long way to go in this method. 3D printing makes it possible to use different materials. In addition, other authors who used this method to produce MNs used biocompatible resins [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis paper presents the proposed designs of two different shapes of MNs based on the tip structure of 1- and 3-bevel hypodermic needles, with a relatively simple form that can facilitate their implementation in 3D printing with class 1 biocompatible resin that has high mechanical strength and puncture capacity. Finite element analysis (FEA) makes it possible to observe and validate the mechanical behavior in the presence of the loads applied to each MN structure. A mathematical model is also obtained that relates the inner and outer diameter of the MN within established ranges of these design parameters. 3D printing of the two designs was also implemented in the Form2-Formlabs printer to observe which of these designs achieves the best print resolutions.\u003c/p\u003e"},{"header":"2. Theoretical Analysis","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Structural Design\u003c/h2\u003e \u003cp\u003eThe structural design of MNs is based on creating a one-plane bevel-tipped needle and three bevel-tip. These structures are relatively simple and allow an adequate load distribution on the network, avoiding structural damage during the MN insertion process.\u003c/p\u003e \u003cp\u003eThe basic shape of the MNs is a cylinder with a length of 450 \u0026micro;m. The inner and outer diameter ranges are established to use any value within them because the dimensions for the manufacture of MNs greatly depend on the available resources. The ranges maintain the values of inner and outer diameters without exceeding the sizes of an MN, without affecting the mechanical behavior of the MN, and with a good safety factor for future use in the medical area.\u003c/p\u003e \u003cp\u003eIn the inner diameter range, a minimum of 30 \u0026micro;m is established and a maximum of 250 \u0026micro;m for the outer diameter. If this value is outstripped, it would be outside the accepted dimensions for an MN [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Mechanical simulations establish that this diameter range ensures that the MN can overcome the force necessary to pierce the skin without presenting mechanical failures and provide a safety factor of 4. Values similar and close to this inner diameter range have been used in medical device designs, such as needles, that prove suitable for use [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFor the manufacture of MNs, the printing quality will determine the diameter values used to obtain a good structure with good printing resolutions.\u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003ch2\u003e2.1.1. Microneedle with the tip in the form of a one-plane bevel-tipped needle (MNTB1).\u003c/h2\u003e \u003cp\u003eThe structure of this MN has a tip forming an angle (\u003cem\u003eθ\u003c/em\u003e) of 45\u0026deg; between the lateral surface and the beveled plane, a length of 450 \u0026micro;m and a range of inner diameter (\u003cem\u003eβ\u003c/em\u003e) and outer diameter (\u003cem\u003eα\u003c/em\u003e). A single-plane beveled hypodermic needle inspires the shape of this tip, the tip of which acts as a cutting edge, see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eThis MN is characterized by generating a force asymmetrically, causing the tissue cut to occur at a compensating angle depending on the bevel angle, needle flexibility, and tissue properties [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.1.2. Microneedle with the tip in the form of 3 bevel-tip (MNTB3).\u003c/h2\u003e \u003cp\u003eThe MN structure of the tip is inspired by a hypodermic needle three bevel tip, i.e., it has three areas, where the force exerted by the skin will be distributed during penetration has two shear angles, \u003cem\u003eθ\u003c/em\u003e\u003csub\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;30\u0026deg; and \u003cem\u003eθ\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;35\u0026deg; as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, a length of 450 \u0026micro;m and a range of inner diameter (\u003cem\u003eβ\u003c/em\u003e) and outer diameter (\u003cem\u003eα\u003c/em\u003e).\u003c/p\u003e \u003cp\u003eThe shape of the tip that formed by the uppercuts (bevel 2 and 3) makes this MN have a sharper tip, a fundamental characteristic of the performance of the needle insertion because the contact area between the MN is mainly concentrated in the part of the pointed tip at the time of the initial cut [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Theoretical microneedle Mechanical Analysis\u003c/h2\u003e \u003cp\u003eThe stratum corneum is the principal cutaneous layer that mainly influences the viscoelastic property of the skin; this property is responsible for generating resistance when the skin is perforated, providing the maximum insertion resistance of an MN [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], causing compression on the MN structure. It is necessary to overcome the skin's opposition for the MN to penetrate the skin.\u003c/p\u003e \u003cp\u003eThe evaluation of MN mechanical stresses is carried out simulating the forces to which it's subjected just at the moment of insertion; this is the case where the MN is exposed to maximum resistance by the skin.\u003c/p\u003e \u003cp\u003eThe axial force that the microneedle can withstand without producing irreversible negative effects on its structure is provided with the compressive or yield stress (\u003cem\u003eσy\u003c/em\u003e); this stress is comprised by Eq.\u0026nbsp;(1) that relates the cross-section (\u003cem\u003eA\u003c/em\u003e) of the analyzed section with the force that the MN can withstand without breaking (\u003cem\u003eF\u003c/em\u003e\u003csub\u003e\u003cem\u003ecompressive\u003c/em\u003e\u003c/sub\u003e).\u003c/p\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({\\sigma }_{y}=\\frac{{F}_{compressive}}{A}\\)\u003c/span\u003e\u003c/span\u003e,\u003c/p\u003e \u003cp\u003e(1)\u003c/p\u003e \u003cp\u003eIt is necessary to know the values of some mechanical properties of the material to be worked with to study the forces on the MN, which is class 1 biocompatible resin. These material properties are tensile strength of 73 MPa and a young's modulus of 2,9 GPa since the values obtained in the results depend directly on these properties.\u003c/p\u003e \u003cp\u003eIn addition, the \u003cem\u003eF\u003c/em\u003e\u003csub\u003e\u003cem\u003ecompressive\u003c/em\u003e\u003c/sub\u003e used was 0,5 N because this value is adequate to simulate the force needed to pierce the skin in a hydration condition because it is within ranges established in other works [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Finite Element Analysis (Fea)","content":"\u003cp\u003eThe main reason for the mechanical analysis of MNs is to determine the behavior of the structure, and the material is chosen since they must be able to correctly support the skin\u0026apos;s resistance without generating adverse effects such as buckling of the MN structure during the insertion process. A fundamental factor that decreases the probability of buckling is to have an adequate wall thickness.\u003c/p\u003e\n\u003cp\u003eThe simulations of the two-needle designs performed with the biocompatible resin class 1, with the mechanical properties mentioned above and a Poisson coefficient of 0,35 established by resins with similar characteristics was used [25, 26].\u003c/p\u003e\n\u003cp\u003eThe results obtained with these simulations show that MN design presents lower Von Misses stresses and deformations [23]. Other results are the values of the available ranges of inner and outer diameter with the mechanical simulations. With these, a mathematical model is taken that generalizes the relationship of these two design parameters within the ranges obtained, ensuring the mechanical integrity of the MN within these ranges and also allows the MN to have an adequate safety factor for its future medical implementation.\u003c/p\u003e\n\u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003e3.1. Initial mechanical analysis of microneedle structures\u003c/h2\u003e\n \u003cp\u003eFor this mechanical analysis, the two MN designs (MNTB1 and MNTB3) were evaluated under the same conditions, a compression force of 0,5N and specific geometric dimensions: MN length of 450 \u0026micro;m, inner diameter (\u003cem\u003e\u0026beta;\u003c/em\u003e) of 30 \u0026micro;m and outer diameter (\u003cem\u003e\u0026alpha;\u003c/em\u003e) of 250 \u0026micro;m, values within the initially known ranges.\u003c/p\u003e\n \u003cp\u003eThese simulations showed that the MN design with the lowest Von Misses stresses was MNTB1, with a maximum stress of 12.451 MPa see Fig.\u0026nbsp;3 and a maximum strain of 0,0015442. While the MNTB3 design presented a maximum stress of 15.903 MPa see Fig.\u0026nbsp;4 and maximum deformation of 0,0013586.\u003c/p\u003e\n \u003ch2\u003e3.2. Generalized outer and inner diameter ranges for design MNTB1 with a factor of safety of 4\u003c/h2\u003e\n \u003cp\u003eThe generalized ranges were obtained for the MN design with the lowest Von Misses stresses, MNTB1.\u003c/p\u003e\n \u003cp\u003eWith the minimum diameter of 30 \u0026micro;m, the outer diameter varied in the mechanical simulation until finding the value where the Von Misses forces were as close as possible to 18.250 MPa (since this is the permissible value for safety factor 4). Considering that the material\u0026apos;s tensile strength is 73 MPa, the minimum outer diameter was found around 208 \u0026micro;m, where a maximum Von Misses stress of 17.818 MPa, \u003cstrong\u003esee\u003c/strong\u003e Fig.\u0026nbsp;5, and with the maximum outer diameter of 250 \u0026micro;m the same procedure was performed. However, varying the inner diameter until finding the maximum value where the MN did not exceed the tensile strength of the resin, being this 134 \u0026micro;m, maximum inner diameter, with a Von Misses stress of 17.931 MPa, see Fig.\u0026nbsp;6. Table\u0026nbsp;1 shows the values obtained for the inner and outer diameter.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eResult of inner and outer diameter ranges.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDiameter (\u0026micro;m)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMin. value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMax. value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInner\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e134\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOuter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e250\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\"\u003e\n \u003ch2\u003e3.3. A mathematical model for generalizing the outer/inner ratio diameter within the obtained ranges\u003c/h2\u003e\n \u003cp\u003eA mathematical model that generalizes the relationship of the diameters within the ranges obtained was developed. One characteristic of the model is flexibility in the microneedle design since any diameter value within the ranges can be used; this can be very useful when manufacturing the microneedle. On many occasions, the available manufacturing resources may limit microneedles\u0026apos; manufacture in micrometer sizes, as specialized technology is required. It also ensures that the MN design has an adequate safety factor for future manufacturing and implementation.\u003c/p\u003e\n \u003cp\u003eFirst, a graph was made to observe the behavior and trend of the data, for which 12 values were chosen within the inner and outer diameter ranges, see Table\u0026nbsp;2. This table also shows that none of the values in this range presents stresses higher than the permissible value for a safety factor of 4, confirming that the design parameters preserve the mechanical integrity of the MN in these ranges. Next, using a fourth-degree polynomial regression, which was the one that perfectly fitted the trend of the data (see Fig.\u0026nbsp;7). Finally, a mathematical model corresponding to the form shown in equation two is obtained for the study.\u003c/p\u003e\n \u003cdiv\u003e\u003cimg src=\"data:image/png;base64,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\"\u003e\u003c/div\u003e\n \u003cp\u003eWhere A presents a value of 4,9622e-7, B of -1,8167e-4, C of 0,0256, D of -1,1671, and E of 224,3235, values found in MATLAB when doing the polynomial regression, also, a data correlation of 0,9993 was obtained, which indicates that the behavior of the data and the fourth-degree polynomial regression have a very high and good correlation.\u003c/p\u003e\n \u003cp\u003eThe inner or outer diameter values found by this mathematical model will allow the design to present a Von Misses stress similar or close to 17.998 MPa, which is the average value of the data obtained in this study.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eInner and outer diameter values within the established range, and von misses stress values were obtained in each case.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInner diameter (\u0026micro;m)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOuter diameter (\u0026micro;m)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVon Misses stresses (MPa)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.818\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.043\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.170\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e218\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.976\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.983\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.080\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e232\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.860\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.090\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.979\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.931\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"4. Microneedle 3d Printing","content":"\u003cp\u003eThe 3D printing of the MNs was performed with the Form 2- Formlabs printer and a class 1 biocompatible resin. The cleaning and curing processes of the MNs were performed following the protocols given by the material manufacturer.\u003c/p\u003e \u003cp\u003eThe MNTB1 design was the one manufactured in 3D printing, where a good printing resolution was observed. It could be seen that the printed format did correspond to the modeled design and that the experimental geometric dimensions were very close to the theoretical ones.\u003c/p\u003e \u003cp\u003eTwo printouts MNs were fabricated, one with the minimum values and the other with the maximum diameters. Although the impression achieved a physical appearance very similar to the proposed design, there was resin clogging in the inner holes of the MN, both for the impression of minimum and maximum diameter values. Still, for the maximum values, the clogging was lower. See Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e, observing that a better printing resolution is obtained the larger the dimensions to be printed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"5. Conclusions And Future Outlook","content":"\u003cp\u003eThis research paper shows useful and relevant information for the design and fabrication of MN, analyzing the mechanical behavior of the structures designed, finding the ranges of inner and outer diameters necessary so that the MN did not have mechanical failures and that these dimensions allowed the 3D printing. A mathematical model was also found to generalize the outer and inner diameter ratios in the obtained ranges.\u003c/p\u003e \u003cp\u003eThe FEA simulations showed that the MNTB1 design was the one that got the lowest von Misses stresses, and this design was then the one with the best mechanical behavior. Also, the inner and outer diameters range allows the needle to behave mechanically appropriately during insertion. The range is between 30 \u0026micro;m and 134 \u0026micro;m for the inner diameter and 208 \u0026micro;m to 250 \u0026micro;m for the outer diameter. In addition, simulations showed that the design, dimensions, and material support the force exerted by the skin at the time of penetration of the MN, which shows that it can be coupled in a method of transdermal drug delivery.\u003c/p\u003e \u003cp\u003eThe mathematical model obtained that generalizes the relation between inner and outer diameter allows the design to be universal in manufacturing because there is not a single value of diameters. The model does not fail mechanically and can be printed.\u003c/p\u003e \u003cp\u003eThe fabrication of the MNTB1 model in 3D printing showed a high resolution of impressive appearance and dimensions very similar to those of the designed model. However, the inner cavity of the MN presented resin clogging, as the MNs are in micrometer orders that make the 3D printing process more rigorous. 3D printing still has many challenges to face and must be studied in depth to perfect this method more and more, especially in very small details such as inner holes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u0026nbsp;\u003c/strong\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e Conceptualization, F.F. and I.V., methodology, F.F., P.C. and O.C., software, I.V. and O.C., validation, I.V., O.C. and F.F., formal analysis, F.F., I.V. and O.C., investigation, I.V., O.C. and F.F., resources, O.C. and F.F., data curation, I.V. and P.C, writing\u0026mdash;original draft preparation, I.V., writing\u0026mdash;review and editing, O.C and F.F., visualization, F.F., supervision, F.F., project administration, O.C. and F.F. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e The authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e Thanks to Universidad Aut\u0026oacute;noma de Occidente, the institution that supported this research project and the UAO young researcher of I.Villota. Also, to Brandon Quintero for guidance on ANSYS software and simulations.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eXu J, Xu D, Xuan X, He H. Advances of microneedles in biomedical applications. Molecules. 2021. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/molecules26195912\u003c/span\u003e\u003cspan address=\"10.3390/molecules26195912\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen BZ, He MC, Zhang XP, Fei WM. \u0026middot;Cui Y,\u0026middot;Guo XD. A novel method for fabrication of coated microneedles with homogeneous and controllable drug dosage for transdermal drug delivery. 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Cure-state dependent viscoelastic Poisson\u0026rsquo;s ratio of LY5052 epoxy resin. Adv Manuf Polym Compos Sci. 2017. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://10.1080/20550340.2017.1348002\u003c/span\u003e\u003cspan address=\"https://10.1080/20550340.2017.1348002\" 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":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"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":"Microneedles, Transdermal drug delivery, finite element analysis, 3D printing","lastPublishedDoi":"10.21203/rs.3.rs-1490579/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1490579/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis article presents the microneedles analysis where the design parameters studied were length, inner and outer diameter range. The ANSYS software was used to analyze the mechanical behavior of the microneedles. Following this, the range of inner and outer diameters were completed by mechanical simulations, getting from 30 μm to 134 μm, as the inner diameter range and 208 μm to 250 μm as the outer diameter range. With these ranges, a mathematical model was made using fourth-order polynomial regression, with a correlation of 0,9993. This mathematical model generalizes the relationship of the inner diameter to the outer diameter within the ranges, ensuring a safety factor of four, where Von Misses forces of the microneedle are around 17.931 MPa. In addition, the microneedle concept was made by 3D printing using a biocompatible resin of class 1. The features presented by the microneedle designed in this work make it a promising option to be implemented in a transdermal drug delivery device.\u003c/p\u003e","manuscriptTitle":"Microneedle, a one-plane bevel-tipped fabrication by 3D printing process.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-21 16:30:28","doi":"10.21203/rs.3.rs-1490579/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":"7350c4df-119c-4642-b796-336a8332fa34","owner":[],"postedDate":"April 21st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-05-12T08:22:46+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-21 16:30:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1490579","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1490579","identity":"rs-1490579","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}