Sequential treatment of infectious bone defects with three dimensional-printed body temperature-responsive shape memory scaffold coated with metal-polyphenol layers

Background: Infectious bone defects are characterized by persistent bacterial invasion and an immune microenvironment imbalance, which significantly hinders bone regeneration. Recently, numerous bone repair materials have been developed to address the complex pathological microenvironment associated with infectious bone defects. However, dynamic changes in the defect size after infectious debridement pose a significant challenge for achieving effective bone integration of artificial bone grafts. Therefore, there is a need to develop an integrated scaffold with antibacterial, immunomodulatory, and osteogenic properties to achieve filling of irregular bone defects. Methods: Using low-temperature printing combined with the freeze-drying technology, a shape-memory scaffold with a biomimetic porous structure of cancellous bones was fabricated by compositing left-handed poly(L-lactic acid)-trimethylene carbonate (PLLA-TMC) with citric acid-modified hydroxyapatite (CHA). The scaffold (PT/CHA) was further coated with a metal-polyphenol network tannic acid-magnesium (TA-Mg) on its surface through the "mussel" effect, enabling the sequential treatment of infectious bone defects. Results: The scaffold can adaptively integrate with defect interfaces at the physiological temperature (37°C), achieving superior bone integration performance. The incorporation of citric-acid-modified hydroxyapatite effectively optimizes the polymer-inorganic phase printing ink system, significantly enhancing the mechanical strength and mineralization capacity of the scaffold. Meanwhile, the external tannic-acid-magnesium metal-polyphenol coating (TA-Mg) demonstrates excellent pathogen clearance properties both in vitro and in vivo. It also influences macrophage polarization to regulate the immune microenvironment, ultimately promoting bone regeneration in infectious bone defects. Conclusions: The PT/CHA@TA-Mg scaffold achieves bone integration through adaptive filling and enables the multi-stage treatment of infectious bone defects via antibacterial, immune-regulatory, and osteogenic differentiation.