Porous composite hydrogels with improved MSC survival for robust epithelial sealing around implants and M2 macrophage polarization

The application of mesenchymal stem cell (MSC)-based therapy is expected to make a significant con-tribution to the improvement of epithelial sealing around implants. However, there is currently no opti-mal MSC delivery biomaterial for clinical application in peri-implant epithelium (PIE) integration. In this study, we show that injectable photo-cross-linkable porous gelatin methacryloyl (GelMA)/silk fibroin gly-cidyl methacrylate (SilMA) hydrogels encapsulating gingival tissue-derived MSCs (GMSCs) are a simple and practical approach for re-epithelization applications. The hydrogels played a prominent role in sup-porting the proliferation, survival, and spread of GMSCs. Moreover, it was found that GMSCs-laden Porous GelMA/SilMA hydrogels could significantly upregulate the hemidesmosomes (HDs)-related genes and pro-teins expression and promote M2 polarization while inhibiting M1 polarization in vitro . Based on a rat model of early implant placement, application of the MSC-loaded hydrogels could enhance the protein ex-pression of LAMA3 and BP180 (COL17A1) at the implant-PIE interface and reduce horseradish peroxidase (HRP) penetration between the implants and PIE. Noticeably, hydrogel-based MSC therapy contributed to augmenting M2 macrophage infiltration at two time points in the gingival connective tissue around implants. These findings demonstrated that GMSCs-laden Porous GelMA/SilMA hydrogels could facilitate epithelial sealing around implants and M2-polarized macrophages and may be a novel and facile thera-peutic strategy for implant-PIE integration.Statement of significance In the case of poor integration between the implant and gingival epithelium, peri-implantitis can develop, which is one of the main causes of implant failure. While stem cell therapy has tremendous potential for addressing this issue, poor cell survival and engraftment compromise the effectiveness of the therapy. Due to the excellent modifiable and tunable properties of gelatin and silk fibroin, injectable photo-cross-linkable porous hydrogels were developed using gelatin methacryloyl (GelMA) and silk fibroin glycidyl methacrylate (SilMA) as delivery vehicles for gingiva-derived MSCs (GMSCs). Porous GelMA/SilMA not only enhanced the proliferation and viability of GMSCs but also promoted their immunomodulatory ca-pability for favorable epithelial sealing around implants. Overall, GMSCs-seeded porous hydrogels could be promising strategies for re-epithelization treatment.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

This study demonstrates that injectable photo-cross-linkable porous GelMA/SilMA hydrogels encapsulating GMSCs can facilitate epithelial sealing around implants and promote M2-polarized macrophage infiltration. The hydrogels support the proliferation, survival, and spread of GMSCs, and upregulate HDs-related genes and proteins expression. The application of these hydrogels in a rat model of implant placement enhances protein expression at the implant-PIE interface and reduces HRP penetration.