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 in vitro testing confirmed biocompatibility, enzyme-responsive degradation, and capability to support stem cell differentiation. Further in vivo 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.