AccScience Publishing / IJB / Volume 10 / Issue 5 / DOI: 10.36922/ijb.4069
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RESEARCH ARTICLE

Methacrylic anhydride-assisted one-step in situ extrusion 3D bioprinting of collagen hydrogels for enhanced full-thickness skin regeneration

Xiaxia Yang1,2 ,  Linyan Yao1,2 ,  Wenhua Li1,2 ,  Xiaodi Huang1,2 ,  Na Li1,2 ,  Jianxi Xiao1,2*
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1 State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu, China
2 Gansu Engineering Research Center of Medical Collagen, Lanzhou, Gansu, China
IJB 2024, 10(5), 4069 https://doi.org/10.36922/ijb.4069
Submitted: 28 June 2024 | Accepted: 7 August 2024 | Published: 9 August 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Full-thickness skin injuries cause extended inflammation, compromised angiogenesis, and protracted wound healing, presenting considerable health risks. Herein, we introduce an innovative technique utilizing methacrylic anhydride (MA)-enhanced, one-step in situ extrusion 3D bioprinting of collagen hydrogels, specifically engineered for the effective repair of full-thickness skin injuries. This method capitalizes on the inherent bioactivity of collagen, surmounting its mechanical constraints via a streamlined, one-step extrusion process enabled by MA. The resultant biomaterial ink, an optimized mix of collagen, MA, and photoinitiator, demonstrates superior printability, mechanical robustness, and stability, making it an ideal candidate for direct application to wound sites. The bioprinted collagen scaffolds exhibit improved mechanical strength, reduced swelling, and enhanced resistance to enzymatic degradation, providing a durable matrix for cell proliferation and tissue in-growth. In vitro assessments reveal that the scaffolds support human foreskin fibroblast adhesion, proliferation, and migration, creating a conducive environment for skin regeneration. In vivo evaluations, conducted using a rat full-thickness skin injury model, further validate the scaffold’s efficacy in promoting rapid and orderly tissue repair, characterized by accelerated re-epithelialization and organized collagen deposition. This MA-enhanced, in situ extrusion 3D bioprinting technique generates collagen hydrogel scaffolds that significantly accelerate wound healing, offering promising advancements in tissue engineering and regenerative medicine.

Keywords
Collagen
Extrusion 3D bioprinting
Full-thickness skin regeneration
Funding
This work was supported by grants from the National Natural Science Foundation of China (grant nos. 22074057 and 22205089), the Natural Science Foundation of Gansu Province (grant no. 20YF3FA025), and the Fundamental Research Funds for the Central Universities (grant no. lzujbky-2021-it15).
Conflict of interest
The authors declare no competing interest.
References
  1. Park H, Patil TV., Dutta SD, et al. Extracellular matrix-bioinspired anisotropic topographical cues of electrospun nanofibers: a strategy of wound healing through macrophage polarization. Adv. Healthcare Mater. 2024;13:2304114. doi: 10.1002/adhm.202304114
  2. Todorova K, Mandinova A. Novel approaches for managing aged skin and nonmelanoma skin cancer. Adv. Drug Delivery Rev. 2020;153:18-27. doi: 10.1016/j.addr.2020.06.004
  3. Eyerich S, Eyerich K, Traidl-Hoffmann C, Biedermann T. Cutaneous barriers and skin immunity: differentiating a connected network. Trends Immunol. 2018;39:315-327. doi: 10.1016/j.it.2018.02.004
  4. Cao X, Lin X, Li N, Zhao X, Zhou M, Zhao Y. Animal tissue-derived biomaterials for promoting wound healing. Mater. Horiz. 2023;10:3237-3256. doi: 10.1039/D3MH00411B
  5. Zhou C, Sheng C, Chen J, et al. Gradual hydrogel degradation for programable repairing full-thickness skin defect wound. Chem. Eng. J. 2022;450:138200. doi: 10.1016/j.cej.2022.138200
  6. Wang Y, Luo M, Li T, Xie C, Li S, Lei B. Multi-layer-structured bioactive glass nanopowder for multistage-stimulated hemostasis and wound repair. Bioact. Mater. 2023;25:319-332. doi: 10.1016/j.bioactmat.2023.01.019
  7. Luo Y, Yi X, Liang T, et al. Autograft microskin combined with adipose-derived stem cell enhances wound healing in a full-thickness skin defect mouse model. Stem Cell Res. Ther. 2019;10:279. doi: 10.1186/s13287-019-1389-4
  8. Cuono C, Langdon R, McGuire J. Use of cultured epidermal autografts and dermal allografts as skin replacement after burn injury. Lancet. 1986;327: 1123-1124. doi: 10.1016/S0140-6736(86)91838-6
  9. Moore TC, Schayer RW. Histidine decarboxylase activity of autografted and allografted rat skin. Transplantation. 1969;7:99-104. doi: 10.1097/00007890-196902000-00002
  10. Priya SG, Jungvid H, Kumar A. Skin tissue engineering for tissue repair and regeneration. Tissue Eng., Part B. 2008;14:105-118. doi: 10.1089/teb.2007.0318
  11. Tottoli EM, Rossella D, Genta I, Chiesa E, Pisani S, Conti B. Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics. 2020;12:735. doi: 10.3390/pharmaceutics12080735
  12. Chouhan D, Dey N, Bhardwaj N, Mandal BB. Emerging and innovative approaches for wound healing and skin regeneration: current status and advances. Biomaterials. 2019;216:119267. doi: 10.1016/j.biomaterials.2019.119267
  13. Liu H, Dong J, Du R, Gao Y, Zhao P. Collagen study advances for photoaging skin. Photodermatol. Photoimmunol. Photomed. 2024;40:e12931. doi: 10.1111/phpp.12931
  14. Yang W, Meyers MA, Ritchie RO. Structural architectures with toughening mechanisms in nature: a review of the materials science of Type-I collagenous materials. Prog. Mater. Sci. 2019;103:425-483. doi: 10.1016/j.pmatsci.2019.01.002
  15. Amirrah IN, Lokanathan Y, Zulkiflee I, Wee MFMR, Motta A, Fauzi MB. A comprehensive review on Collagen Type I development of biomaterials for tissue engineering: from biosynthesis to bioscaffold. Biomedicines. 2022; 10:2307. doi: 10.3390/biomedicines10092307
  16. Lin K, Zhang D, Macedo MH, Cui W, Sarmento B, Shen G. Advanced Collagen‐based biomaterials for regenerative biomedicine. Adv. Funct. Mater. 2019;29: 1804943. doi: 10.1002/adfm.201804943
  17. Ruszczak Z. Effect of collagen matrices on dermal wound healing. Adv. Drug Delivery Rev. 2003;55:1595-1611. doi: 10.1016/j.addr.2003.08.003
  18. Gajbhiye S, Wairkar S. Collagen fabricated delivery systems for wound healing: a new roadmap. Biomater. Adv. 2022;142:213152. doi: 10.1016/j.bioadv.2022.213152
  19. Sharma S, Rai VK, Narang RK, Markandeywar TS. Collagen-based formulations for wound healing: a literature review. Life Sci. 2022;290:120096. doi: 10.1016/j.lfs.2021.120096
  20. Mathew-Steiner SS, Roy S, Sen CK. Collagen in wound healing. Bioengineering. 2021;8:63. doi: 10.3390/bioengineering8050063
  21. Wang Y, Wang Z, Dong Y. Collagen-based biomaterials for tissue engineering. ACS Biomater. Sci. Eng. 2023;9: 1132-1150. doi: 10.1021/acsbiomaterials.2c00730
  22. Shi S, Wang L, Song C, Yao L, Xiao J. Recent progresses of collagen dressings for chronic skin wound healing. Collagen Leather. 2023;5:31. doi: 10.1186/s42825-023-00136-4
  23. Chattopadhyay S, Raines RT. Collagen-based biomaterials for wound healing. Biopolymers. 2014;101:821-833. doi: 10.1002/bip.22486
  24. Bacakova M, Pajorova J, Broz A, et al. A two-layer skin construct consisting of a collagen hydrogel reinforced by a fibrin-coated polylactide nanofibrous membrane. Int. J. Nanomed. 2019;14:5033-5050. doi: 10.2147/IJN.S200782
  25. Wang Y, Zhang Y, Li T, et al. Adipose mesenchymal stem cell derived exosomes promote keratinocytes and fibroblasts embedded in collagen/platelet-rich plasma scaffold and accelerate wound healing. Adv. Mater. 2023;35:2303642. doi: 10.1002/adma.202303642
  26. Liu J, Garcia J, Leahy L, et al. 3D printing of multifunctional conductive polymer composite hydrogels. Adv. Funct. Mater. 2023;33:2214196. doi: 10.1002/adfm.202214196
  27. Boyer C, Blasco E, Ke C. Unleashing the potential of 3D printing: bridging chemistry and applications. Small. 2023;19:2309837. doi: 10.1002/smll.202309837
  28. Vijayavenkataraman S, Lu WF, Fuh JYH. 3D bioprinting of skin: a state-of-the-art review on modelling, materials, and processes. Biofabrication. 2016;8:032001. doi: 10.1088/1758-5090/8/3/032001
  29. Shapira A, Noor N, Asulin M, Dvir T. Stabilization strategies in extrusion-based 3D bioprinting for tissue engineering. Appl. Phys. Rev. 2018;5:041112. doi: 10.1063/1.5055659
  30. Donderwinkel I, Hest JCMv, Cameron NR. Bio-inks for 3D bioprinting: recent advances and future prospects. Polym. Chem. 2017;8:4451. doi: 10.1039/C7PY00826K
  31. Mu X, Agostinacchio F, Xiang N, et al. Recent advances in 3D printing with protein-based inks. Prog. Polym. Sci. 2021;115:101375. doi: 10.1016/j.progpolymsci.2021.101375

32 Lee A, Hudson AR, Shiwarski DJ, et al. 3D bioprinting of collagen to rebuild components of the human heart. Science. 2019;365:482-487. doi: 10.1126/science.aav9051

  1. Guo C, Wu J, Zeng Y, Li H. Construction of 3D bioprinting of HAP/collagen scaffold in gelation bath for bone tissue engineering. Regener. Biomater. 2023;10:rbad067. doi: 10.1093/rb/rbad067
  2. Liu Y, Luo X, Wu W, et al. Dual cure (thermal/photo) composite hydrogel derived from chitosan/collagen for in situ 3D bioprinting. Int. J. Biol. Macromol. 2021; 182:689-700. doi: 10.1016/j.ijbiomac.2021.04.058
  3. Suo H, Zhang J, Xu M, Wang L. Low-temperature 3D printing of collagen and chitosan composite for tissue engineering. Mater. Sci. Eng. C. 2021;123:111963. doi: 10.1016/j.msec.2021.111963
  4. Stepanovska J, Otahal M, Hanzalek K, Supova M, Matejka R. pH modification of high-concentrated collagen bioinks as a factor affecting cell viability, mechanical properties, and printability. Gels. 2021;7:252. doi: 10.3390/gels7040252
  5. Yoon H, Lee J, Yim H, Kim G, Chun W. Development of cell-laden 3D scaffolds for efficient engineered skin substitutes by collagen gelation. RSC Adv. 2016;6:21439. doi: 10.1039/C5RA19532B
  6. Kim W, Kim GH. An innovative cell-printed microscale collagen model for mimicking intestinal villus epithelium. Chem. Eng. J. 2018;334:2308-2318. doi: 10.1016/j.cej.2017.12.001
  7. Yeo MG, Kim GH. A cell-printing approach for obtaining hASC-laden scaffolds by using a collagen/polyphenol bioink. Biofabrication. 2017;9:025004. doi: 10.1088/1758-5090/aa6997
  8. Lee J, Yeo M, Kim W, Koo Y, Kim GH. Development of a tannic acid cross-linking process for obtaining 3D porous cell-laden collagen structure. Int. J. Biol. Macromol. 2018;110:497-503. doi: 10.1016/j.ijbiomac.2017.10.105
  9. Lee J, Kim G. 3D hierarchical nanofibrous collagen scaffold fabricated using fibrillated collagen and pluronic F-127 for regenerating bone tissue. ACS Appl. Mater. Interfaces. 2018;10:35801–35811. doi: 10.1021/acsami.8b14088
  10. Lee HJ, Kim YB, Ahn SH, et al. A new approach for fabricating Collagen/ECM-based bioinks using preosteoblasts and human adipose stem cells. Adv. Healthcare Mater. 2015;4:1359-1368. doi: 10.1002/adhm.201500193
  11. Chen C, Xu H, Liu X, et al. 3D printed collagen/silk fibroin scaffolds carrying the secretome of human umbilical mesenchymal stem cells ameliorated neurological dysfunction after spinal cord injury in rats. Regener. Biomater. 2022;9:rbac014. doi: 10.1093/rb/rbac014
  12. Stepanovska J, Supova M, Hanzalek K, Broz A, Matejka R. Collagen bioinks for bioprinting: a systematic review of hydrogel properties, bioprinting parameters, protocols, and bioprinted structure characteristics. Biomedicines. 2021;9:1137. doi: 10.3390/biomedicines9091137
  13. Lee JM, Suen SKQ, Ng WL, Ma WC, Yeong WY. Bioprinting of Collagen: considerations, potentials, and applications. Macromol. Biosci. 2021;21:2000280. doi: 10.1002/mabi.202000280
  14. Matinong AME, Chisti Y, Pickering KL, Haverkamp RG. Collagen extraction from animal skin. Biology. 2022;11:905. doi: 10.3390/biology11060905
  15. Fauzi MB, Lokanathan Y, Aminuddin BS, Ruszymah BHI, Chowdhury SR. Ovine tendon collagen: extraction, characterisation and fabrication of thin films for tissue engineering applications. Mater. Sci. Eng. C. 2016;68:163-171. doi: 10.1016/j.msec.2016.05.109
  16. Diamantides N, Wang L, Pruiksma T, et al. Correlating rheological properties and printability of collagen bioinks: the effects of riboflavin photocrosslinking and Ph. Biofabrication. 2017;9:034102. doi: 10.1088/1758-5090/aa780f
  17. Mondy WL, Cameron D, Timmermans J, et al. Computer-aided design of microvasculature systems for use in vascular scaffold production. Biofabrication. 2009;1:035002. doi: 10.1088/1758-5082/1/3/035002
  18. Logan ME, Zaim MT. Histologic stains in dermatopathology. J. Am. Acad. Dermatol. 1990;22:820-830. doi: 10.1016/S0190-9622(08)81173-5
  19. Fu Z, Naghieh S, Xu C, Wang C, Sun W, Chen X. Printability in extrusion bioprinting. Biofabrication. 2021;13:033001. doi: 10.1088/1758-5090/abe7ab
  20. Suess PM, Smith SA, Morrissey JH. Platelet polyphosphate induces fibroblast chemotaxis and myofibroblast differentiation. J. Thromb. Haemostasis. 2020;18: 3043-3052. doi: 10.1111/jth.15066
  21. Zhao M, Wang J, Zhang J, et al. Functionalizing multi-component bioink with platelet-rich plasma for customized in-situ bilayer bioprinting for wound healing. Mater. Today Bio. 2022;16:100334. doi: 10.1016/j.mtbio.2022.100334
  22. Ding X, Yu Y, Li W, Zhao Y. In situ 3D-bioprinting MoS2 accelerated gelling hydrogel scaffold for promoting chronic diabetic wound healing. Matter. 2023; 6:1000-1014. doi: 10.1016/j.matt.2023.01.001
  23. Santefort AL, Yuya PA, Shipp DA. Dynamic covalent exchange induced cyclization in poly (methacrylic anhydride). Polym. Chem. 2022;13:4502-4510. doi: 10.1039/D2PY00488G
  24. Cavallo A, Kayal T, Mero A, et al. Marine Collagen-based bioink for 3D bioprinting of a Bilayered skin model. Pharmaceutics. 2023;15:1331. doi: 10.3390/pharmaceutics15051331
  25. Kang D, Wang W, Li Y, Ma Y, Huang Y, Wang J. Biological macromolecule hydrogel based on recombinant Type I Collagen/Chitosan scaffold to accelerate full-thickness healing of skin wounds. Polymers. 2023;15:3919. doi: 10.3390/polym15193919
  26. Osidak EO., Karalkin PA., Osidak MS, et al. Viscoll collagen solution as a novel bioink for direct 3D bioprinting. J. Mater. Sci.: Mater. Med. 2019;30:31. doi: 10.1007/s10856-019-6233-y
  27. Yannas I, Tzeranis D, So PT. Surface biology of collagen scaffold explains blocking of wound contraction and regeneration of skin and peripheral nerves. Biomed. Mater. 2016;11:014106. doi: 10.1088/1748-6041/11/1/0A14106
  28. Ma L, Gao C, Mao Z, Zhou J, Shen J. Biodegradability and cell-mediated contraction of porous collagen scaffolds: the effect of lysine as a novel crosslinking bridge. J. Biomed. Mater. Res., Part A. 2004;71A:334–342. doi: 10.1002/jbm.a.30170
  29. Albanna M, Binder KW, Murphy SV, et al. In situ bioprinting of autologous skin cells accelerates wound healing of extensive excisional full-thickness wounds. Sci. Rep. 2019;9:1856. doi: 10.1038/s41598-018-38366-w
  30. Wei Q, Wang Y, Wang H, et al. Photo-induced adhesive carboxymethyl chitosan-based hydrogels with antibacterial and antioxidant properties for accelerating wound healing. Carbohydr. Polym. 2021;278:119000. doi: 10.1016/j.carbpol.2021.119

 

 

 

 

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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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