Water-Insoluble, Thermostable, Crosslinked Gelatin Matrix for Soft Tissue Implant Development

Viktória Varga; László Smeller; Róbert Várdai; Bence Kocsis; Ibolya Zsoldos; Sara Cruciani; Renzo Pala; István Hornyák

doi:10.3390/ijms25084336

Water-Insoluble, Thermostable, Crosslinked Gelatin Matrix for Soft Tissue Implant Development

Int J Mol Sci. 2024 Apr 14;25(8):4336. doi: 10.3390/ijms25084336.

Authors

Viktória Varga^{1

2}, László Smeller³, Róbert Várdai^{4

5}, Bence Kocsis², Ibolya Zsoldos², Sara Cruciani⁶, Renzo Pala⁶, István Hornyák^{1

2}

Affiliations

¹ Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary.
² Department of Materials Science and Technology, University of Győr, 9026 Győr, Hungary.
³ Department of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, Hungary.
⁴ Laboratory of Plastics and Rubber Technology, Department of Physical Chemistry and Materials Science, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, 1111 Budapest, Hungary.
⁵ Research Centre for Natural Sciences, Institute of Materials and Environmental Chemistry, 1111 Budapest, Hungary.
⁶ Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.

Abstract

In this present study, the material science background of crosslinked gelatin (GEL) was investigated. The aim was to assess the optimal reaction parameters for the production of a water-insoluble crosslinked gelatin matrix suitable for heat sterilization. Matrices were subjected to enzymatic degradation assessments, and their ability to withstand heat sterilization was evaluated. The impact of different crosslinkers on matrix properties was analyzed. It was found that matrices crosslinked with butanediol diglycidyl ether (BDDE) and poly(ethylene glycol) diglycidyl ether (PEGDE) were resistant to enzymatic degradation and heat sterilization. Additionally, at 1 v/v % crosslinker concentration, the crosslinked weight was lower than the starting weight, suggesting simultaneous degradation and crosslinking. The crosslinked weight and swelling ratio were optimal in the case of the matrices that were crosslinked with 3% and 5% v/v BDDE and PEGDE. FTIR analysis confirmed crosslinking, and the reduction of free primary amino groups indicated effective crosslinking even at a 1% v/v crosslinker concentration. Moreover, stress-strain and compression characteristics of the 5% v/v BDDE crosslinked matrix were comparable to native gelatin. Based on material science measurements, the crosslinked matrices may be promising candidates for scaffold development, including properties such as resistance to enzymatic degradation and heat sterilization.

Keywords: biomaterials; crosslinked gelatin; material science; scaffold development.

MeSH terms

Biocompatible Materials / chemistry
Cross-Linking Reagents* / chemistry
Epoxy Resins*
Gelatin* / chemistry
Hot Temperature
Materials Testing
Polyethylene Glycols / chemistry
Solubility
Spectroscopy, Fourier Transform Infrared
Sterilization / methods
Tissue Scaffolds / chemistry
Water* / chemistry

Substances

Gelatin
Cross-Linking Reagents
Water
Polyethylene Glycols
Biocompatible Materials
Quetol 651
Epoxy Resins

Grants and funding

This research was supported by the Hungarian National Research, Development and Innovation Office, (OTKA K-125174, K-139230, and PD-143327), by the Ministry of Innovation and Technology of Hungary from the NRDI Fund (ÚNKP-22-4-II-SE-17, 2020-1.1.6-JÖVO-2021-00010, 2020-1.1.6-JÖVO-2021-00013; RRF-2.1.2.-12-2022-0001, TKP2021-EGA-25, TKP2021-EGA-21, and TKP2021-EGA-23). The research was also supported by grants from the National Institute on Aging (R01AG055395, R01AG068295, R01AG070915), the National Institute of Neurological Disorders and Stroke (R01NS100782), the National Cancer Institute (R01CA255840), and the Scientific and Innovation Office of Semmelweis University (STIAKFI007) grants, as well as the iP-Osteo project funding from the European Union’s HORIZON 2020 MSCA-RISE Marie Skłodowska-Curie Research and Innovation Staff Exchange Research Programme under grant agreement no. 823981. The Central Library of Semmelweis University also kindly provided funding for open access publication fees. The research was financed by the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary within the framework of the Molecular Biology Thematic Programme of Semmelweis University.