Sericin-based biomaterial for craniomaxillofacial regeneration: Preclinical evidence and translational potential.

Significant craniomaxillofacial (CMF) bone defects after trauma, tumor removal, or congenital disabilities are a major clinical challenge. Therefore, new methods are continually sought to improve treatment effectiveness. In this context, next-generation biomaterials deserve special attention. Sericin, a protein component of silk, demonstrates regenerative potential. Current evidence suggests that sericin actively stimulates osteogenesis by promoting the differentiation of osteoprogenitor cells and upregulating key markers, including Runx2, osteocalcin, and osteopontin. In addition, it exhibits a favorable biocompatibility profile and promising immunomodulatory properties. By exerting anti-inflammatory effects, sericin may promote a pro-healing polarization of M2 macrophages and reduce TNF-α expression. The antimicrobial potential of sericin-based biomaterials is also highlighted, though the evidence remains debated and further validation is needed, particularly for grafts and scaffolds used in CMF regeneration. Sericin also appears to promote angiogenesis and the organized deposition of mineralized extracellular matrix, which are crucial factors in bone regeneration. In preclinical animal models, sericin-based biomaterials have shown statistically significant improvements in the healing of calvarial, alveolar, and long bone defects. Despite these encouraging findings, the translation of sericin into clinical practice remains limited, with only two human studies available, primarily for minor applications in oral surgery. This review summarizes the current literature focusing on sericin-based biomaterials and relates the available evidence to potential applications in CMF regeneration. In a structured manner, it begins with the physical and biological properties of sericin, proceeds to cellular and tissue interactions, and presents preclinical and clinical evidence, critically evaluating the advantages and limitations.