Proanthocyanidins modification of the mineralized collagen scaffold based on synchronous self-assembly/mineralization for bone regeneration.

Proteoglycans (PG) is crucial for regulating collagen formation and mineralization during bone tissue development. A wide variety of PG-modified collagen scaffolds have been proposed for bone engineering application to promote biological responses and work as artificial matrices that guide tissue regeneration. However, poor performance of theses biomaterials against infections has led to an unmet need for clinical prevention. Therefore, we utilized proanthocyanidins (PA) to simulate the functions of PG, including mediating the collagen assembly and intrafibrillar mineralization, to optimize scaffolds performance. The excellent antibacterial properties of PA can endow the scaffolds with anti-infection effects in the process of tissue regeneration. When PA was added during fibrillogenesis, the collagen fibrils appeared irregular aggregation and the mineralization degree was reduced. In contrast, the addition of PA after collagen self-assembly improved the latter's ability to act as a deposition template and remarkably promoted mineral ions infiltration, thus enhancing intrafibrillar mineralization. The PA-modified scaffold displayed a highly hydrophilicity behaviour and long-term resistance to degradation. The sustained release of PA effectively inhibited the activity of Staphylococcus aureus. The scaffold also showed excellent biocompatibility and improved bone regeneration in calvarial critical-size defect models. The application of PA enables a dual-function scaffold with favourable intrafibrillar mineralization and anti-bacterial properties for bone regeneration.