A Lignin‐Based Coating to Improve Tricalcium Phosphate Bioceramic‐Mediated Osteoimmune Reaction and Osteogenesis

ABSTRACT Beta‐tricalcium phosphate (TCP) bioceramic is a widely used artificial bone substitute, but its rapid degradation and inflammatory activation inhibit complete bone healing. Here, we synthesize a novel lignin‐incorporated polyurethane (LPP) exhibiting a temperature‐induced sol–gel transition, which can form a hydrogel at body temperature. This copolymer is further applied as a dual‐functional coating onto TCP porous scaffolds for bone tissue engineering. Our results demonstrate that the polyurethane coating effectively delays the degradation of TCP both in vitro and in vivo. The incorporation of lignin endows the polyurethane backbone with the capacity to reduce immune cell infiltration and promote neovascularization, thus enhancing the osteoinduction in TCP. For the implantation of in vivo femoral defects, the TCP‐LPP scaffold achieves satisfactory bone regeneration, which is attributed to moderate degradation rate, enhanced osteoinductivity, and upregulation of N6‐methyladenosine methylation. In summary, a new strategy of lignin coating with intrinsic antioxidant activity is developed to optimize the regenerative outcomes of TCP bone substitutes.