Effects of simvastatin gel on bone regeneration in alveolar defects in miniature pigs

Currently, the most commonly used treatment methods for repairing alveolar furcation defects are periodontal guided tissue regeneration （GTR） and bone grafting. The objective of this study was to investigate the effects of simvastatin/methylcellulose gel on bone regeneration in alveolar defects in miniature pigs. Methods Alveolar defects were produced in 32 teeth （the third and fourth premolars） of 4 miniature pigs. The 32 experimental teeth were divided into 5 groups comprising control （C） and treatment （T） teeth： （1） empty defects without gel （group CO, n=4）; （2） defects injected with methylcellulose gel （group C1, n=4）; （3） defects injected with 0.5 rag/50 pl simvastatin/methylcellulose gel （group T1, n=8）; （4） defects injected with 1.5 mg/50 μl simvastatin/methylcellulose gel （group T2, n=8）; and （5） defects injected with 2.2 mg/50 μl simvastatin/methylcellulose gel （group T3, n=8）. Every week after surgery, the furcation sites were injected once with gel. At the eighth week afte（ surgery, the 4 pigs were sacrificed and underwent macroscopic observation, descriptive histologic examination, and regenerate bone quantitative histologic examination. Results At 8 weeks after surgery, the defect sites in the treatment groups were completely filled in with new bone and fibrous tissue. There was little new bone in the CO and C1 groups, and only a small number of osteoblasts and proliferative vessels could be seen on microscopic examination. Conclusions Miniature pigs are an ideal experimental animal for establishing a model of alveolar defects using a surgical method. Local application of simvastatin/methylcellulose gel can stimulate the regeneration of alveolar bone in furcation defect sites, because it promotes the proliferation of osteoblasts. The best dose of simvastatin gel to stimulate bone regeneration is 0.5 mg.

Sequentially releasing self-healing hydrogel fabricated with TGFβ3-microspheres and bFGF to facilitate rat alveolar bone defect repair

Resorption and loss of alveolar bone leads to oral dysfunction and loss of natural or implant teeth. Biomimetic delivery of growth factors based on stem cell recruitment and osteogenic differentiation, as the key steps in natural alveolar bone regenerative process, has been an area of intense research in recent years. A mesoporous self-healing hydrogel(DFH) with basic fibroblast growth factor(bFGF) entrapment and transforming growth factor β3(TGFβ3)-loaded chitosan microspheres(CMs) was developed. The formulation was optimized by multiple tests of self-healing, in-bottle inversion, SEM, rheological, swelling rate and in vitro degradation. In vitro tubule formation assays, cell migration assays, and osteogenic differentiation assays confirmed the ability of DFH to promote blood vessels, recruit stem cells, and promote osteogenic differentiation. The optimum DFH formula is 0.05 ml 4ArmPEG-DF(20%) added to 1 ml CsGlu(2%) containing bFGF(80 ng) and TGFβ3-microspheres(5 mg). The results of in vitro release studied by Elisa kit, indicated an 95% release of b FGF in7 d and long-term sustained release of TGFβ3. For alveolar defects rat models, the expression levels of CD29 and CD45, the bone volume fraction, trabecular number, and trabecular thickness of new bone monitored by Micro-CT in DFH treatment groups were significantly higher than others(*P < 0.05, vs Model). HE and Masson staining show the same results.In conclusion, DFH is a design of bionic alveolar remodelling microenvironment, that is in early time microvessels formed by b FGF provide nutritious to recruited endogenous stem cells, then TGFβ3 slowly released speed up the process of new bones formation to common facilitate rat alveolar defect repair. The DFH with higher regenerative efficiency dovetails nicely with great demand due to the requirement of complicated biological processes.

Treatment of critical bone defects using calcium phosphate cement and mesoporous bioactive glass providing spatiotemporal drug delivery

Calcium phosphate cements (CPC) are currently widely used bone replacement materials with excellent bioactivity, but have considerable disadvantages like slow degradation. For critical-sized defects, however, an improved degradation is essential to match the tissue regeneration, especially in younger patients who are still growing. We demonstrate that a combination of CPC with mesoporous bioactive glass (MBG) particles led to an enhanced degradation in vitro and in a critical alveolar cleft defect in rats. Additionally, to support new bone formation the MBG was functionalized with hypoxia conditioned medium (HCM) derived from rat bone marrow stromal cells. HCM-functionalized scaffolds showed an improved cell proliferation and the highest formation of new bone volume. This highly flexible material system together with the drug delivery capacity is adaptable to patient specific needs and has great potential for clinical translation.