Injectable stress relaxation gelatin-based hydrogels with positive surface charge for adsorption of aggrecan and facile cartilage tissue regeneration

Abstract

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.

Gelatin methacryloyl as environment for chondrocytes and cell delivery to superficial cartilage defects

“…While gelMA has been evaluated for the use in cartilage regeneration, many studies rely on the use of cell lines (Zhou et al., 2018 ), animal derived cells (L. Han et al., 2017 ; M.‐E. Han et al., 2017 ; Mouser, 2018 ; Wang et al., 2021 ) or very young donors (Boere et al., 2014 ) thus making them less applicable for translational research. Other studies using human chondrocyte sources (Brown et al., 2017 ; Gu et al., 2020 ) often focus on material characterization and only superficially describe effects on the cellular level.…”

Is Microfracture Alone Enough?

“…Another approach worth mentioning consists of a modified gelatin hydrogel that absorbs proteoglycans secreted by chondrocytes near the cartilage tissue in situ and quickly forms an adequate chondrocyte survival microenvironment. Wang et al evaluated this therapeutic method, and the in vivo and in vitro results showed that the hydrogels were effective and expressed efficient biocompatibility, while promoting the tissue repair of cartilage defects [54].…”

Hydrogels for Treatment of Different Degrees of Osteoarthritis

“…Internal studies show that the hydrogel structure can be well-integrated with surrounding host tissues. Wang K.-Y. et al (2021a) and others synthesized modified gelatin Gel-EPL, Gel-B, GelEPL/B using ε-poly-L-lysine, and phenylboronic acid as raw materials.…”