Photosensitive and extracellular matrix-mimicking hydrogels promote the tendon-bone healing in rotator cuff injury

The healing of the tendon-bone interface remains a significant challenge due to the lack of suitable bioactive materials for promoting interface regeneration. To address this, we developed a photosensitive hydrogel system designed to mimic the extracellular matrix. This system is based on light-induced imine crosslinking between type I collagen (Col I) and o-nitrobenzyl alcohol (NB)-modified hyaluronic acid (HANB). Experimental results demonstrate that the hydrogel (Col I-HANB) exhibits excellent controllability, low swelling rate, biodegradability, and tissue-adhesive properties. Using a fluorescent dye (8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt, HPTS) as a model molecule, we confirmed that the hydrogel enables localized and sustained release, high-lighting its potential as a drug-delivery platform for tissue engineering. To further enhance tendon-bone interface repair, the hydrogel was functionalized with two key components: (I) The E7 peptide, known for its stem cell-homing properties, was covalently immobilized into the hydrogel network via conjugation to bovine serum albumin (BSA) and followed by imine-ligation between UV-triggered aldehyde generation from HANB and BSA’s amino groups; and (II) Kartogenin (KGN)-loaded nanoparticles (KGN-NPs) were incorporated to potentially promote chondrogenic differentiation, with release assays confirming sustained KGN delivery over 21 days. The composite hydrogel demonstrated excellent biocompatibility in cytotoxicity and live/dead assays. Importantly, in a rabbit rotator cuff tear model, it effectively promoted fibrocartilage regeneration and significantly improved tendon-bone healing, creating a favorable microenvironment for repair. The results above indicate that the hydrogel system provides a good microenvironment for rotator cuff injury repair and is a promising scaffold applied in treatment of rotator cuff injury. The construction diagram of Col I-HANB hydrogel and the application in promoting rotator cuff injury repair. HANB: ortho-nitrobenzyl alcohol (NB)-modified hyaluronic acid (HA). KGN: Kartogenin. The KGN incorporated to the hydrogel can induce the differentiation of mesenchymal stem cells into chondrocytes in the tendon-bone interface. The structure and composition of tendon-bone interface are shown on the right side of the figure: From top to bottom, there are tendon, non-mineralized fibrocartilage, mineralized fibrocartilage, and bone.