Development of bioresorbable smart injectable hydrogels based on thermo-responsive copolymer integrated bovine serum albumin bioconjugates for accelerated healing of excisional wounds

Abstract

One of the major challenges in wound healing is the development of suitable hydrogels that are injectable, biocompatible with multiple functionalities and properties such as high mechanical, tissue adhesiveness, and swelling properties. However, these hydrogels should not elicit any immunological response and synthesis steps should be easier and tunable according to the requirements. Considering these properties, we synthesized a thermo-sensitive triblock copolymer consisting of bovine serum albumin (BSA) protein capable of leveraging the needs for a proper wound closure and tissue regeneration on excisional injuries. Firstly, the triblock copolymer consisting of poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA) was synthesized and then the copolymer was grafted with BSA to yield BSA-PCLA bioconjugates. Aqueous solutions of free-flowing bioconjugate sol at room temperature can transform to gel at physiological temperature with high viscoelastic properties. Subcutaneous injection of BSA-PCLA bioconjugate sol into the back of Sprague-Dawley rats formed gel immediately and found to be bioresorbable after 5 weeks without significant toxicity at implantation sites. BSA-PCLA bioconjugate gel exhibited good adhesive property to major organs including liver, heart, and spleen when compared with control PCLA gel. When tested for in vivo wound closure trials, the BSA-PCLA gels showed rapid wound contraction compared to the PCLA and the control. The increased angiogenesis and collagen deposition were confirmed from the histological studies of the samples. These highly adhesive, biocompatible, biodegradable, thermos-sensitive bioconjugate gels show promising potential in wound healing and tissue regeneration without any additional biofactors or inorganic nanoparticles.