Biodegradable metabotissugenic citrate-based polymer derived self-sealing pro-regenerative membrane for tendon anti-biofouling and repair

Tendon stem/progenitor cells (TSPCs) are crucial for intrinsic regeneration of injured tendons which consume a substantial amount of energy relying on the tricarboxylic acid (TCA) cycle. Citric acid, the key substrate of the TCA cycle, emerges as a promising candidate for regulating energy metabolism. However, sustainable methods in providing energy metabolic substrates across the whole regenerating process has been neglected. Herein, a metabotissugenic membrane consisting of poly(octamethylene citrate) and L-lysine diisocyanate, POCL₁₀, was developed to consistently biodegrade and provide citrate substrates. Furthermore, the POCL₁₀ membrane exhibited self-sealing properties due to the introduction of strong hydrogen bonds and demonstrated anti-biofouling capacity in vitro. Intriguingly, POCL₁₀ showed excellent regenerative capability by promptly upregulating TSPC proliferation, energy metabolism and differentiation. In vivo, POCL₁₀ was effortlessly wrapped around the injured Achilles tendon showcasing with anti-tissue adhesion and prominent collagen organization along with strengthened biomechanical properties. Hence, the development of POCL expands the reservoir of available biodegradable citrate-based biomaterials and provides a unique metabotissugenic biomaterial platform for tendon anti-biofouling and repair.