Injectable FHE+BP composites hydrogel with enhanced regenerative capacity of tendon-bone interface for anterior cruciate ligament reconstruction

Abstract

Features of black phosphorous (BP) nano sheets such as enhancing mineralization and reducing cytotoxicity in bone regeneration field have been reported. Thermo-responsive FHE hydrogel (mainly composed of oxidized hyaluronic acid (OHA), poly-ε-L-lysine (ε-EPL) and F127) also showed a desired outcome in skin regeneration due to its stability and antibacterial benefits. This study investigated the application of BP-FHE hydrogel in anterior cruciate ligament reconstruction (ACLR) both in in vitro and in vivo, and addressed its effects on tendon and bone healing. This BP-FHE hydrogel is expected to bring the benefits of both components (thermo-sensitivity, induced osteogenesis and easy delivery) to optimize the clinical application of ACLR and enhance the recovery. Our in vitro results confirmed the potential role of BP-FHE via significantly increased rBMSC attachment, proliferation and osteogenic differentiation with ARS and PCR analysis. Moreover, In vivo results indicated that BP-FHE hydrogels can successfully optimize the recovery of ACLR through enhancing osteogenesis and improving the integration of tendon and bone interface. Further results of Biomechanical testing and Micro-CT analysis [bone tunnel area (mm2) and bone volume/total volume (%)] demonstrated that BP can indeed accelerate bone ingrowth. Additionally, histological staining (H&E, Masson and Safranin O/fast green) and immunohistochemical analysis (COL I, COL III and BMP-2) strongly supported the ability of BP to promote tendon-bone healing after ACLR in murine animal models.

The role of smart polymeric biomaterials in bone regeneration: a review

“…Infused with the TNF-alpha antagonist etanercept (ETN), the hydrogel mitigates debris-induced osteolysis through sustained ETN release, thereby reducing aseptic inflammation. For anterior cruciate ligament (ACL) repair, a thermos-responsive BP-FHE BP, primarily F127, oxidized hyaluronic acid (OHA), poly-epsilon-L-lysine (epsilon-EPL)) hydrogel was proven to promote mineralization, skin, and bone regeneration while reducing cytotoxicity, optimizing ACLR clinical use and recovery ( Cho et al, 2023 ). Sui et al (2023) L-PRF-based chitosan (CS)-hydroxyapatite (HAP) composite scaffold provides mechanical stability, sustained release, and enhanced cytotoxicity for bone regeneration.…”

“…Frontiers in Bioengineering and Biotechnology frontiersin.org mineralization, skin, and bone regeneration while reducing cytotoxicity, optimizing ACLR clinical use and recovery (Cho et al, 2023). Sui et al (2023) L-PRF-based chitosan (CS)hydroxyapatite (HAP) composite scaffold provides mechanical stability, sustained release, and enhanced cytotoxicity for bone regeneration.…”