Background Cartilage injury and pathological degeneration are reported in millions of patients globally. Cartilages such as articular hyaline cartilage are characterized by poor self-regeneration ability due to lack of vascular tissue. Current treatment methods adopt foreign cartilage analogue implants or microfracture surgery to accelerate tissue repair and regeneration. These methods are invasive and are associated with the formation of fibrocartilage, which warrants further exploration of new cartilage repair materials. The present study aims to develop an injectable modified gelatin hydrogel. Method The hydrogel effectively adsorbed proteoglycans secreted by chondrocytes adjacent to the cartilage tissue in situ, and rapidly formed suitable chondrocyte survival microenvironment modified by ε-poly-L-lysine (EPL). Besides, dynamic covalent bonds were introduced between glucose and phenylboronic acids (PBA). These bonds formed reversible covalent interactions between the cis−diol groups on polyols and the ionic boronate state of PBA. PBA-modified hydrogel induced significant stress relaxation, which improved chondrocyte viability and cartilage differentiation of stem cells. Further, we explored the ability of these hydrogels to promote chondrocyte viability and cartilage differentiation of stem cells through chemical and mechanical modifications. Results In vivo and in vitro results demonstrated that the hydrogels exhibited efficient biocompatibility. EPL and PBA modified GelMA hydrogel (Gel-EPL/B) showed stronger activity on chondrocytes compared to the GelMA control group. The Gel-EPL/B group induced the secretion of more extracellular matrix and improved the chondrogenic differentiation potential of stem cells. Finally, thus hydrogel promoted the tissue repair of cartilage defects. Conclusion Modified hydrogel is effective in cartilage tissue repair.

Background: Diabetic wounds are a disturbing and rapidly growing clinical problem. A novel peptide, parathyroid hormone related peptide (PTHrP-2), is assumed as multifunctional factor in angiogenesis, fibrogenesis and reepithelization. This study aims to test PTHrP-2 efficiency and mechanism in wound healing. Methods: Through repair phenomenon in vivo some problems were detected, and further research on their mechanisms was made. In vivo therapeutic effects of PTHrP-2 were determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 were determined by proliferation, migration, Vascular Endothelial Grown Factor and collagen I secretion of cells and Akt/ Erk1/2 pathway change. In vitro indirect effects of PTHrP-2 was study via exosomes. Exosomes from PTHrP-2 untreated and treated HUVECs and HFF-1 cells were insolated and identified. Exosomes were co-cultured with original cells, HUVECs or HFF-1 cells, and epithelial cells. Proliferation and migration and pathway change were observed. PTHrP-2-HUVEC-Exos were added into in vivo wound to testify its hub role in PTHrP-2 indirect effects in wound healing. Results: In vivo, PTHrP-2 exerted multifunctional pro-angiogenesis, pro-firbogenesis and re-epithelization effects. In vitro, PTHrP-2 promoted proliferation and migration of endothelial and fibroblast cells, but had no effect on epithelial cells. Therefore, we tested PTHrP-2 indirect effects via exosomes. PTHrP-2 intensified intercellular communication between endothelial cells and fibroblasts and initiated endothelial-epithelial intercellular communication. PTHrP-2-HUVEC-Exos played a hub role in PTHrP-2 indirect effects in wound healing.Conclusion: These findings of this study indicated that PTHrP-2, a multifunctional factor, could promote wound healing via synergistic multicellular stimulating and exosomal activities.

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