Abstract
The fragile nature of porous bioceramic substitutes cannot match the toughness of bone, which limits the use of these materials in clinical load-bearing applications. Statins can enhance bone healing, but it could show rhabdomyolysis/inflammatory response after overdosing. In this study, the drug-containing bone grafts were developed from poly(lactic acid-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles encapsulating simvastatin (SIM) (SIM-PP NPs) loaded within an appropriately mechanical bioceramic scaffold (BC). The combination bone graft provides dual functions of osteoconduction and osteoinduction. The mechanical properties of the bioceramic are enhanced mainly based on the admixture of a combustible reverse-negative thermoresponsive hydrogel (poly(N-isopropylacrylamide base). We showed that SIM-PP NPs can increase the activity of alkaline phosphatase and osteogenic differentiation of bone marrow stem cells. To verify the bone-healing efficacy of this drug-containing bone grafts, a nonunion radial endochondral ossification bone defect rabbit model (N = 3/group) and a nonunion calvarial intramembranous defect Sprague Dawley (SD) rat model (N = 5/group) were used. The results indicated that SIM-PP NPs combined with BC can improve the healing of nonunion bone defects of the radial bone and calvarial bone. Therefore, the BC containing SIM-PP NPs may be appropriate for clinical use as a synthetic alternative to autologous bone grafting that can overcome the problem of determining the clinical dosage of simvastatin drugs to promote bone healing.
Highlights
Bones comprise the majority of both volume and weight in the human body, and their most important function is to allow the body’s action and support the body structure
This study demonstrated that the combination product of a porous BC scaffold combined with SIM-PP NPs can improve the healing of bone defects in a rabbit radial endochondral ossification bone defect model and an standard deviation (SD) rat calvarial intramembranous defect model
The porous bioceramic (BC) scaffold combined with SIM-PP NPs with sustained-release of simvastatin produced both osteoinductive and osteoconductive effects that accelerated bone regeneration
Summary
Bones comprise the majority of both volume and weight in the human body, and their most important function is to allow the body’s action and support the body structure. The most common bone defects in clinical treatment include serious bone fractures, nonunion bone fractures, bone defects caused by osteomyelitis, postoperative defects caused by bone tumors, vertebral body collapse, and other acetabular bone defects from artificial joint reconstruction [1]. Surgical techniques currently used to treat bone defects rely on different alternatives, including homologous bone grafts provided by a musculoskeletal tissue bank (allograft), autologous vascularized bone grafts, prostheses, or heterologous bone grafts (xenograft), each of which has specific advantages, complications, and drawbacks [1]. Autologous bone grafts remain the gold standard in bone repair and regeneration because of the osteogenicity, osteoinductivity, and osteoconductivity associated with this technique [2]. Autologous bone grafts may be resorbed too rapidly as they can be degraded before bone completed healing [5]
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