Silk Acid as an Implantable Biomaterial for Tissue Regeneration

Abstract Silk fibroin derived from the domesticated silkworm Bombyx mori is a protein‐based biopolymer with low immunogenicity, intrinsic biodegradability, and tunable mechanical properties, showing great potential in biomedical applications. Using chemical modification to alter the primary structure of silk fibroin enables the expanded generation of new silk‐based biomaterials. Inspired by the molecular structure of hyaluronic acid, which is enriched in carboxyl groups, an efficient method with scaling‐up potential to achieve controlled carboxylation of silk fibroin to prepare silk acid (SA) is reported, and the biological properties of SA are further studied. The SA materials show tunable hydrophilicity and enzymatic degradation properties at different carboxylation degrees (CDs). Subcutaneous implantation in mice for up to 1 month reveals that the SA materials with a high CD present enhanced degradation while causing a mild foreign‐body response, including a low inflammatory response and reduced fibrotic encapsulation. Immunofluorescence analysis further indicates that the SA materials show pro‐angiogenesis properties and promote M2‐type macrophage polarization to facilitate tissue regeneration. This implies great promise for SA materials as a new implantable biomaterial for tissue regeneration.