Incorporating simvastatin/poloxamer 407 hydrogel into 3D-printed porous Ti ₆ Al ₄ V scaffolds for the promotion of angiogenesis, osseointegration and bone ingrowth

Abstract

Three-dimensional porous titanium alloys printed via electron beam melting have low stiffness similar to that of cortical bone and are promising scaffolds for orthopedic applications. However, the bio-inert nature of titanium alloy is poorly compatible with bone ingrowth. We previously observed that simvastatin/poloxamer 407 thermosensitive hydrogel induces endogenous angiogenic/osteogenic growth factors and promotes angiogenesis and osteogenesis, but the mechanical properties of this hydrogel are poor. The purpose of this study was to construct 3D-printed porous titanium scaffolds (pTi scaffolds) filled with simvastatin/hydrogel and evaluate the effects of this composite on osseointegration, bone ingrowth and neovascularization using a tibial defect rabbit model. Four and eight weeks after implantation, the bone volume, bone mineral density, mineral apposition rate, and push-in maximum force of the pTi scaffolds filled with simvastatin/hydrogel were significantly higher than those without simvastatin (p < 0.05). Moreover, filling with simvastatin/hydrogel significantly enhanced vascularization in and around the pTi scaffolds, and a significant correlation was observed between the volume of new bone and neovascularization (p < 0.01). In conclusion, incorporating simvastatin/poloxamer 407 hydrogel into pTi scaffolds significantly improves neovascularization, osseointegration and bone ingrowth.

Inhibition of cathepsin K promotes osseointegration of titanium implants in ovariectomised rats

“…After acquiring the 3D images, the peri-implant volume-of-interest of 1 mm was established manually, and the threshold value was adjusted appropriately to distinguish trabecular bone from bone marrow. Inveon Research Workplace 3.0 software (Siemens) was used to automatically compute BV/TV, BMD and the following trabecular bone morphological parameters: Tb.N, Tb.Sp and Tb.Th4445.…”

Statin-Induced Nitric Oxide Signaling: Mechanisms and Therapeutic Implications

“…The involvement of both mature endothelial cells and circulating EPCs after statin treatment suggests that statins can induce both angiogenesis and vasculogenesis [89][90][91]. Therefore, statins have been loaded into tissue engineering scaffolds made from mesoporous hydroxyapatite microspheres or titanium to induce angiogenesis in the structure [92,93]. The ability of cells to form tubes after statin exposure is mediated by both the PI3K/Akt pathway (evidenced by suppression of migration by a PI3k inhibitor) and AMPK pathways.…”

Clinical, industrial, and research perspectives on powder bed fusion additively manufactured metal implants

“…This basic proof of concept has been established in cp-Ti with a range of biocompatible fillers [122]. Infiltration of a simvastatin loaded hydrogel into a Ti-6Al-4 V scaffold showed significantly greater vascularisation, osseointegration, and bone ingrowth in a rabbit model compared to equivalent structures without a secondary phase [123]. Alternatively, a larger and more controlled volume of material may be delivered by integrating the second phase inside a physical reservoir, i.e.…”