Strontium-Substituted\nNanohydroxyapatite Containing\nBiodegradable 3D Printed Composite Scaffolds for Bone Regeneration

Treatment of large-size bone defects is difficult, and\nacquiring\nautografts may be challenging due to limited availability. A synthetic\npatient-specific bone substitute can be developed by using 3D printing\ntechnologies in such cases. In the present study, we have developed\nphotocurable composite resins with poly(trimethylene carbonate) (PTMC)\ncontaining a high percentage of biodegradable bioactive strontium-substituted\nnanohydroxyapatite (SrHA, size 30–70 nm). These photocurable\nresins have then been employed to develop high-surface-area 3D-printed\nbone substitutes using the digital light processing (DLP) technique.\nTo enhance the surface area of the 3D-printed substitute, cryogels\nalone and functionalized with bioactive components of bone morphogenetic\nprotein (BMP) and zoledronic acid (ZA) were filled within the 3D-printed\nscaffold/substitute. The scaffolds were tested in vitro for biocompatibility\nand functionality in vivo in two therapeutically relevant rat models\nwith large bone defects (4 mm). The porosities of 3D printed scaffolds\nwere found to be 60.1 ± 0.9%, 72.9 ± 0.5%, and 74.3 ±\n1.6% for PTMC, PTMC-HA, and PTMC-SrHA, respectively, which is in the\nrange of cancellous bone (50–95%). The thermogravimetric analysis\ndemonstrated the fabrication of 3D printed composites with HA and\nSrHA concentrations of 51.5 and 57.4 wt %, respectively, in the PTMC\nmatrix. The tensile Young’s modulus (<i>E</i>), compressive\nmoduli, and wettability increased post incorporation of SrHA and HA\nin the PTMC matrix. In vitro and in vivo results revealed that SrHA\nintegrated into the PTMC matrix exhibited good physicochemical and\nbiological properties. Furthermore, the osteoactive molecule-functionalized\n3D printed composite scaffolds were found to have an adequate osteoconductive\nand osteoinductive surface that has shown increased bone regeneration\nand defect repair in both tibial and cranial bone defects. Our findings\nthus support the use of PTMC-SrHA composites as next-generation patient-specific\nsynthetic bioactive biodegradable bone substitutes.