Bone Enzyme-Responsive Biodegradable Poly(propylene fumarate) and Polycaprolactone Polyphosphoester Dendrimer Cross-Linked via Click Chemistry for Bone Tissue Engineering

Traditional polymer systems often rely on toxic initiators or catalysts for cross-linking, posing significant safety risks. For bone tissue engineering, another issue is that the scaffolds often take a longer time to degrade, inconsistent with bone formation pace. Here, we developed an enzyme-responsive biodegradable poly(propylene fumarate) (PPF) and polycaprolactone (PCL) polyphosphoester (PPE) dendrimer cross-linked utilizing click chemistry (EnzDeg-click-PFCLPE scaffold) for enhanced biocompatibility and degradation. The strain-promoted alkyne-azide cycloaddition (SPAAC) offers high efficiency and biocompatibility without harmful agents. The polyphosphoesters render polymer cleavage responsive to alkaline phosphatase (ALP) enzyme in bone formation, ensuring facilitated scaffold biodegradation. The <i>in vitro</i> testing confirmed biocompatibility, enzyme-responsive degradation, and capability to support stem cell differentiation. Further <i>in vivo</i> implantation in rat demonstrated bone regeneration and scaffold integration. In summary, this polymer system combining click chemistry with ALP-responsive biodegradation ensures initial bone support and facilitates scaffold degradation synchronized with the natural bone healing process.