A pH-responsive immunomodulatory scaffold synergistically promotes osteogenesis for enhanced osseointegration in osteoporotic bone

With the increasing aging of the global population, osteoporosis has emerged as a key challenge affecting orthopedic implant survival. Traditional implant surfaces are mostly biologically inert, and in osteoporosis patients, they cannot actively cope with the harsh microenvironment composed of chronic inflammation and low osteogenic capacity, resulting in poor osseointegration and even implant failure. Therefore, this study proposes and verifies a new treatment strategy: to achieve immune regulation and direct bone induction of the microenvironment around the implant under osteoporosis by constructing a multifunctional bioactive scaffold. We constructed a multifunctional composite scaffold TZIF-8-PDA@TC4 by constructing a polydopamine (PDA) coating on the surface of Ti-6Al-4V titanium alloy (TC4) and Zeolite imidazolate framework 8 (ZIF-8) nanoparticles loaded with Tetrandrine (TET). The scaffold has good biocompatibility, drug release, and mechanical properties. We verified its dual functions of immunomodulation and osteogenesis induction through in vitro cellular experiments, demonstrating that it can effectively inhibit the M1 phenotype and promote the M2 phenotype, thereby creating an immune microenvironment conducive to osteoblast function. Finally, the scaffold’s ability to drive robust osseointegration was confirmed in vivo using an osteoporotic rat model. This strategy of actively guiding tissue immunity and regenerative reactions provides a promising solution to solve the current orthopedic implantation field in the osteoporosis environment, and opens up new directions for the design of regenerative biomaterials.