Porosity, pore size and water content (%) of pHEMA hydrogels prepared with different water contents
Water content of the reaction mixture (%)
Porosity (%)
Pore sizes (µm)
Water content after swelling (%)
44
17
40.75 ± 8.59
40.27 ± 1.20
50
33
55.09 ± 7.15
42.80 ± 1.24
55
52
15.24 ± 3.05
47.60 ± 1.34
80
50
15.44 ± 2.05
52.17 ± 0.50
Declarations
Acknowledgments
We acknowledge the support by METU CoE in Biomaterials and Tissue Engineering (BIOMATEN) for the use of the facilities and materials. We also acknowledge Department of Bioengineering and Genetics, Gumushane University, Turkey for the opportunity to study at METU.
Author contributions
DAS: Resources, Data curation, Formal analysis, Investigation, Methodology, Validation, Writing—original draft. CDS: Validation, Writing—review & editing, Supervision. VH: Conceptualization, Methodology, Validation, Visualization, Writing—review & editing, Supervision. All authors read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Ethical approval
Not applicable.
Consent to participate
Not applicable.
Consent to publication
Not applicable.
Availability of data and materials
The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.
Funding
This work was supported by Strategy and Budget Department of Turkiye Republic [BAP-08-11-KB.2016K-121520]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Li NY, Onor GI, Lemme NJ, Gil JA. Epidemiology of peripheral nerve ınjuries in sports, exercise, and recreation in the United States, 2009 – 2018.Phys Sportsmed. 2021;49:355–62. [DOI] [PubMed]
Lopes B, Sousa P, Alvites R, Branquinho M, Sousa AC, Mendonça C, et al. Peripheral nerve injury treatments and advances: one health perspective.Int J Mol Sci. 2022;23:918. [DOI] [PubMed] [PMC]
Baradaran A, El-Hawary H, Efanov JI, Xu L. Peripheral nerve healing: so near and yet so far.Semin Plast Surg. 2021;35:204–10. [DOI] [PubMed] [PMC]
Wieringa PA, Gonçalves de Pinho AR, Micera S, van Wezel RJA, Moroni L. Biomimetic architectures for peripheral nerve repair: a review of biofabrication strategies.Adv Healthc Mater. 2018;7:e1701164. [DOI] [PubMed]
Krauss EM, Weber RV, Mackinnon SE. 52 - Nerve injury, repair, and reconstruction. In: Farhadieh RD, Bulstrode NW, Mehrara BJ, Cugno S, editors. Plastic surgery - principles and practice. Elsevier; 2022. pp. 803–25.
Kasper M, Deister C, Beck F, Schmidt CE. Bench-to-bedside lessons learned: commercialization of an acellular nerve graft.Adv Healthc Mater. 2020;9:e2000174. [DOI] [PubMed]
Narayan SK, Arumugam M, Chittoria R. Outcome of human peripheral nerve repair interventions using conduits: a systematic review.J Neurol Sci. 2019;396:18–24. [DOI] [PubMed]
Xu H, Yu Y, Zhang L, Zheng F, Yin Y, Gao Y, et al. Sustainable release of nerve growth factor for peripheral nerve regeneration using nerve conduits laden with bioconjugated hyaluronic acid-chitosan hydrogel.Composites, Part B. 2022;230:109509. [DOI]
Wolfe EM, Mathis SA, Ovadia SA, Panthaki ZJ. Comparison of collagen and human amniotic membrane nerve wraps and conduits for peripheral nerve repair in preclinical models: a systematic review of the literature.J Reconstr Microsurg. 2023;39:245–53. [DOI] [PubMed]
Xiang L, Cui W. Biomedical application of photo-crosslinked gelatin hydrogels.J Leather Sci Eng. 2021;3:1–24. [DOI]
Alvites RD, Branquinho MV, Sousa AC, Amorim I, Magalhães R, João F, et al. Combined use of chitosan and olfactory mucosa mesenchymal stem/stromal cells to promote peripheral nerve regeneration in vivo.Stem Cells Int. 2021;2021:6613029. [DOI] [PubMed] [PMC]
Abdelbasset WK, Jasim SA, Sharma SK, Margiana R, Bokov DO, Obaid MA, et al. Alginate-based hydrogels and tubes, as biological macromolecule-based platforms for peripheral nerve tissue engineering: a review.Ann Biomed Eng. 2022;50:628–53. [DOI] [PubMed]
Li A, Pereira C, Hill EE, Vukcevich O, Wang A. In vitro, in vivo and ex vivo models for peripheral nerve ınjury and regeneration.Curr Neuropharmacol. 2022;20:344–61. [DOI] [PubMed] [PMC]
Roca FG, Santos LG, Roig MM, Medina LM, Martínez-Ramos C, Pradas MM. Novel tissue-engineered multimodular hyaluronic acid-polylactic acid conduits for the regeneration of sciatic nerve defect.Biomedicines. 2022;10:963. [DOI] [PubMed] [PMC]
Onode E, Uemura T, Hama S, Yokoi T, Okada M, Takamatsu K, et al. Nerve-end capping treatment with a polyglycolic acid conduit for rat sciatic neuroma: a preliminary report.J Reconstr Microsurg. 2022;38:711–20. [DOI] [PubMed]
Grijalvo S, Díaz DD. Graphene-based hybrid materials as promising scaffolds for peripheral nerve regeneration.Neurochem Int. 2021;147:105005. [DOI] [PubMed]
Pozzobon LG, Sperling LE, Teixeira CE, Malysz T, Pranke P. Development of a conduit of PLGA-gelatin aligned nanofibers produced by electrospinning for peripheral nerve regeneration.Chem Biol Interact. 2021;348:109621. [DOI] [PubMed]
Dursun Usal T, Yesiltepe M, Yucel D, Sara Y, Hasirci V. Fabrication of a 3D printed PCL nerve guide: in vitro and in vivo testing.Macromol Biosci. 2022;22:e2100389. [DOI] [PubMed]
Borschel GH, Kia KF, Kuzon WM Jr, Dennis RG. Mechanical properties of acellular peripheral nerve.J Surg Res. 2003;114:133–9. [DOI] [PubMed]
Ma X, Wang M, Ran Y, Wu Y, Wang J, Gao F, et al. Design and fabrication of polymeric hydrogel carrier for nerve repair.Polymers (Basel). 2022;14:1549. [DOI] [PubMed] [PMC]
Zare M, Bigham A, Zare M, Luo H, Rezvani Ghomi E, Ramakrishna S. pHEMA: an overview for biomedical applications.Int J Mol Sci. 2021;22:6376. [DOI] [PubMed] [PMC]
Velasco-Rodriguez B, Diaz-Vidal T, Rosales-Rivera LC, García-González CA, Alvarez-Lorenzo C, Al-Modlej A, et al. Hybrid methacrylated gelatin and hyaluronic acid hydrogel scaffolds. Preparation and systematic characterization for prospective tissue engineering applications.Int J Mol Sci. 2021;22:6758. [DOI] [PubMed] [PMC]
Dodla MC, Alvarado-Velez M, Mukhatyar VJ, Bellamkonda RV. Peripheral nerve regeneration. Chapter 69 - Peripheral nerve regeneration. In: Atala A, Lanza R, Mikos AG, Nerem R, editors. Principles of regenerative medicine (third edition). Boston: Academic Press; 2019. pp. 1223–36.
Min Q, Parkinson DB, Dun XP. Migrating Schwann cells direct axon regeneration within the peripheral nerve bridge.Glia. 2021;69:235–54. [DOI] [PubMed]
Wu P, Tong Z, Luo L, Zhao Y, Chen F, Li Y, et al. Comprehensive strategy of conduit guidance combined with VEGF producing Schwann cells accelerates peripheral nerve repair.Bioact Mater. 2021;6:3515–27. [DOI] [PubMed] [PMC]
Endo T, Kadoya K, Suzuki T, Suzuki Y, Terkawi MA, Kawamura D, et al. Mature but not developing Schwann cells promote axon regeneration after peripheral nerve injury.NPJ Regen Med. 2022;7:12. [DOI] [PubMed] [PMC]
Jessen KR, Mirsky R. Schwann cells in nerve repair and regeneration. In: Phillips JB, Hercher D, Hausner T, editors. Peripheral nerve tissue engineering and regeneration. Springer, Cham; 2022. pp. 385–401.
Huang Q, Cai Y, Zhang X, Liu J, Liu Z, Li B, et al. Aligned graphene mesh-supported double network natural hydrogel conduit loaded with netrin-1 for peripheral nerve regeneration.ACS Appl Mater Interfaces. 2021;13:112–22. [DOI] [PubMed]
Xie HR, Hu LS, Li GY. SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson’s disease.Chin Med J (Engl). 2010;123:1086–92. [PubMed]
Cerda‐Sumbarda YD, Zapata‐Gonzalez I, Licea‐Claverie A, Zizumbo‐Lopez A, F. Ramos‐de Valle L, Espinoza‐Martínez A. Poly(hexylacrylate)Core-poly(ethyleneglycol methacrylate)Shell nanogels as fillers for poly(2-hydroxyethyl methacrylate) nanocomposite hydrogels.Polym Eng Sci. 2019;59:170–81. [DOI]
Shirahama H, Lee BH, Tan LP, Cho NJ. Precise tuning of facile one-pot gelatin methacryloyl (GelMA) synthesis.Sci Rep. 2016;6:31036. [DOI] [PubMed] [PMC]
Smeds KA. Synthesis, characterization, and biomedical applications of novel photocrosslinkable hydrogels and biodendrimers [dissertation]. Duke University; 2002.
Twarużek M, Zastempowska E, Soszczyńska E, Ałtyn I. The use of in vitro assays for the assessment of cytotoxicity on the example of MTT test.Folia Biol. 2018;14:23–32. [DOI]
Hoch E, Schuh C, Hirth T, Tovar GE, Borchers K. Stiff gelatin hydrogels can be photo-chemically synthesized from low viscous gelatin solutions using molecularly functionalized gelatin with a high degree of methacrylation.J Mater Sci Mater Med. 2012;23:2607–17. [DOI] [PubMed]
Shie MY, Lee JJ, Ho CC, Yen SY, Ng HY, Chen YW. Effects of gelatin methacrylate bio-ink concentration on mechano-physical properties and human dermal fibroblast behavior.Polymers (Basel). 2020;12:1930. [DOI] [PubMed] [PMC]
Yousefi F, Kandel S, Pleshko N. Infrared spectroscopic quantification of methacrylation of hyaluronic acid: a scaffold for tissue engineering applications.Appl Spectrosc. 2018;72:1455–66. [DOI] [PubMed]
Dursun Usal T, Yucel D, Hasirci V. A novel GelMA-pHEMA hydrogel nerve guide for the treatment of peripheral nerve damages.Int J Biol Macromol. 2019;121:699–706. [DOI] [PubMed]
Tutar R, Yüce-Erarslan E, İzbudak B, Bal-Öztürk A. Photocurable silk fibroin-based tissue sealants with enhanced adhesive properties for the treatment of corneal perforations.J Mater Chem B. 2022;10:2912–25. [DOI] [PubMed]
Zamboni F, Okoroafor C, Ryan MP, Pembroke JT, Strozyk M, Culebras M, et al. On the bacteriostatic activity of hyaluronic acid composite films.Carbohydr Polym. 2021;260:117803. [DOI] [PubMed]
Khurana B, Ouk TS, Lucas R, Senge MO, Sol V. Photosensitizer-hyaluronic acid complexes for antimicrobial photodynamic therapy (aPDT).J Porphyr Phthalocyanines. 2022;26:585–93. [DOI]
O’Grady BJ, Balotin KM, Bosworth AM, McClatchey PM, Weinstein RM, Gupta M, et al. Development of an N-cadherin biofunctionalized hydrogel to support the formation of synaptically connected neural networks.ACS Biomater Sci Eng. 2020;6:5811–22. [DOI] [PubMed] [PMC]
Xiao S, Zhao T, Wang J, Wang C, Du J, Ying L, et al. Gelatin methacrylate (GelMA)-based hydrogels for cell transplantation: an effective strategy for tissue engineering.Stem Cell Rev Rep. 2019;15:664–79. [DOI] [PubMed]
Noh I, Kim N, Tran HN, Lee J, Lee C. 3D printable hyaluronic acid-based hydrogel for its potential application as a bioink in tissue engineering.Biomater Res. 2019;23:3. [DOI] [PubMed] [PMC]
Roth JG, Huang MS, Li TL, Feig VR, Jiang Y, Cui B, et al. Advancing models of neural development with biomaterials.Nat Rev Neurosci. 2021;22:593–615. [DOI] [PubMed] [PMC]
Camci-Unal G, Cuttica D, Annabi N, Demarchi D, Khademhosseini A. Synthesis and characterization of hybrid hyaluronic acid-gelatin hydrogels.Biomacromolecules. 2013;14:1085–92. [DOI] [PubMed] [PMC]
Wang Y, Ma M, Wang J, Zhang W, Lu W, Gao Y, et al. Development of a photo-crosslinking, biodegradable GelMA/PEGDA hydrogel for guided bone regeneration materials.Materials (Basel). 2018;11:1345. [DOI] [PubMed] [PMC]
Wang Y, Lin C. Study on properties of 3D-printed GelMA hydrogel scaffolds with different nHA contents.J Bioact Compat Polym. 2022;37:392–405. [DOI]
Elkhoury K, Morsink M, Sanchez-Gonzalez L, Kahn C, Tamayol A, Arab-Tehrany E. Biofabrication of natural hydrogels for cardiac, neural, and bone tissue engineering applications.Bioact Mater. 2021;6:3904–23. [DOI] [PubMed] [PMC]
Pooshidani Y, Zoghi N, Rajabi M, Haghbin Nazarpak M, Hassannejad Z. Fabrication and evaluation of porous and conductive nanofibrous scaffolds for nerve tissue engineering.J Mater Sci Mater Med. 2021;32:46. [DOI] [PubMed] [PMC]
Hasirci N, Kilic C, Kömez A, Bahcecioglu G, Hasirci V. Chapter 1: Hydrogels in regenerative medicine.In: Gels handbook. 2016. pp. 1–52. [DOI]
Chen Y, Long X, Lin W, Du B, Yin H, Lan W, et al. Bioactive 3D porous cobalt-doped alginate/waterborne polyurethane scaffolds with a coral reef-like rough surface for nerve tissue engineering application.J Mater Chem B. 2021;9:322–35. [DOI] [PubMed]
Manoukian OS, Arul MR, Rudraiah S, Kalajzic I, Kumbar SG. Aligned microchannel polymer-nanotube composites for peripheral nerve regeneration: small molecule drug delivery.J Control Release. 2019;296:54–67. [DOI] [PubMed] [PMC]
Kilic Bektas C, Hasirci V. Cell loaded GelMA:HEMA IPN hydrogels for corneal stroma engineering.J Mater Sci Mater Med. 2019;31:2. [DOI] [PubMed]
Ferreira CL, Valente CA, Zanini ML, Sgarioni B, Ferreira Tondo PH, Chagastelles PC, et al. Biocompatible PCL/PLGA/Polypyrrole composites for regenerating nerves.Macromol Symp. 2019;383:1800028. [DOI]
Fath MK, Zahedi F, Hashemi ZS, Khalili S. Evaluation of differentiation quality of several differentiation inducers of bone marrow-derived mesenchymal stem cells to nerve cells by assessing expression of beta-tubulin 3 marker: a systematic review.Curr Stem Cell Res Ther. 2021;16:994–1004. [DOI] [PubMed]
Luijerink L, Waters KA, Machaalani R. Immunostaining for NeuN does not show all mature and healthy neurons in the human and pig brain: focus on the hippocampus.Appl Immunohistochem Mol Morphol. 2021;29:e46–56. [DOI] [PubMed]
Tenbaum S, Palmer HG, Arqués O, Chicote I, Puig I. Standardized relative quantification of ımmunofluorescence tissue staining.Research Square [Preprint]. 2012 [cited 2021 Nov 11]. Available from: https://doi.org/10.1038/protex.2012.008
Ruiz IM, Vilariño-Feltrer G, Mnatsakanyan H, Vallés-Lluch A, Monleón Pradas M. Development and evaluation of hyaluronan nanocomposite conduits for neural tissue regeneration.J Biomater Sci Polym Ed. 2021;32:2227–45. [DOI] [PubMed]
Dong X, Liu S, Yang Y, Gao S, Li W, Cao J, et al. Aligned microfiber-induced macrophage polarization to guide schwann-cell-enabled peripheral nerve regeneration.Biomaterials. 2021;272:120767. [DOI] [PubMed]
Ma Y, Wei C, Qi X, Pu Y, Dong L, Xu L, et al. Schistosoma japonicum-derived peptide SJMHE1 promotes peripheral nerve repair through a macrophage-dependent mechanism.Am J Transl Res. 2021;13:1290–306. [PubMed] [PMC]
Ramesh PA, Dhandapani R, Bagewadi S, Zennifer A, Radhakrishnan J, Sethuraman S, et al. Reverse engineering of an anatomically equivalent nerve conduit.J Tissue Eng Regen Med. 2021;15:998–1011. [DOI] [PubMed]
Yang X, Huang L, Yi X, Huang S, Duan B, Yu A. Multifunctional chitin-based hollow nerve conduit for peripheral nerve regeneration and neuroma inhibition.Carbohydr Polym. 2022;289:119443. [DOI] [PubMed]
Zhang H, Guo J, Wang Y, Shang L, Chai R, Zhao Y. Natural polymer-derived bioscaffolds for peripheral nerve regeneration.Advanced Functional Materials. 2022;32:2203829. [DOI]
Cai Y, Huang Q, Wang P, Ye K, Zhao Z, Chen H, et al. Conductive hydrogel conduits with growth factor gradients for peripheral nerve repair in diabetics with non-suture tape.Adv Healthc Mater. 2022;11:e2200755. [DOI] [PubMed]
