Simvastatin loaded chitosan guided bone regeneration membranes stimulate bone healing.

BACKGROUND AND OBJECTIVE: Electrospun chitosan membranes (ESCM) modified with short-chain fatty acids have the ability to control the release of simvastatin (SMV), an anti-cholesterol drug with osteogenic potential, for guided bone regeneration (GBR) applications. This study evaluated in vivo osteogenic effects of rapid short release of SMV (4 weeks) vs long sustained release (8 weeks) from acetic anhydride (AA)-and hexanoic anhydride (HA)-modified ESCMs, respectively. METHODS: AA ESCMs loaded with 10 or 50 µg SMV and HA ESCMs loaded with 50 µg SMV were evaluated for biocompatibility and bone formation at 4 and 8 weeks, in 5 mm critical size rat calvarial defects, using histological evaluation and micro-CT analysis. RESULTS: No severe inflammatory response was noticed around the ESCMs. Less hydrophobic AA membranes showed signs of resorption by week 4 and were almost completely resorbed by week 8 whereas the more hydrophobic HA membranes resorbed slowly, remaining intact over 8 weeks. In micro-CT analysis, 10 µg SMV-loaded AA membranes did not show significant bone formation as compared to non-loaded AA membranes at either evaluation time points. 50 µg SMV-loaded AA membranes stimulated significantly more bone formation than non-loaded AA membranes by week 4 (%bone = 31.0 ± 5.9% (AA50) vs 18.5 ± 13.7% (AA0)) but showed no difference at week 8. HA membranes with 50 µg SMV showed significantly more bone formation as compared to corresponding non-loaded membranes by week 8 (%bone = 61.7 ± 8.9% (HA50) vs 33.9 ± 29.7% (HA0)), though such an effect was not significant at week 4. CONCLUSION: These results indicate that modified ESCMs may be used to control the release of SMV and promote bone healing in GBR applications.

Use of Collagen Matrix Scaffolds as a Substitute for Soft Tissue Augmentation: Case Series.

INTRODUCTION: The presence of keratinized mucosa (KM) around natural teeth is believed to be beneficial in certain restorative, prosthetic, and orthodontic situations. Lack of adequate KM is common and predictably treated by autogenous gingival grafts (AGGs); however, AGGs have the disadvantages of harvest site morbidity, limited donor site availability, and compromised esthetics. CASE PRESENTATION: This case series presents the use of the xenogeneic porcine bilayer collagen matrix (BCM) in increasing the width of attached KM around natural teeth. Patients with a limited amount of KM, shallow vestibule, and aberrant frenum attachment were treated using this graft material. The patients were followed up to 4.5 years postoperatively and were evaluated regarding the amount of KM, gingival margin stability, and tissue esthetics. CONCLUSIONS: Within the limitations of the sample size of patients in this report, the BCM appears to be a viable alternative option to AGG for increasing the width of KM gingiva around teeth. This method resulted in gain of KM, gingival margin stability, vestibular deepening, aberrant frenum elimination, and favorable esthetics in terms of color matching, texture, and contour blending. This xenogeneic graft material could be used in cases where the autogenous graft supply is limited or in highly esthetically demanding cases. Additionally, it could be an alternative option when a second surgical site is not desired by the patient or a less invasive procedure is preferred by the clinician in certain medical conditions. Well-controlled long-term studies are required to validate our limited clinical observations.

Mechanically stable surface-hydrophobilized chitosan nanofibrous barrier membranes for guided bone regeneration.

The use of chitosan based nanofiber membranes in guided bone regeneration (GBR) is limited by its uncontrolled swelling and mechanical instability in aqueous environments. This paper describes the significantly improved stability and properties of surface butyrylated chitosan nanofiber (BCSNF) membranes that greatly enhance their potential in GBR. The BCSNF membranes exhibited an overall degree of substitution of 1.61, an average diameter of 99.3 ± 33.7 nm, and a 75% decrease in swelling with an approximate doubling in suture pull out strengths as compared to unmodified fibers in aqueous environment. In a five week phosphate-buffered saline-lysozyme degradation study, it was found that the remaining mass fraction of BCSNF membranes was 11.5% more than that of unmodified fibers. In vitro, the BCSNF membranes were found to support the adhesion and proliferation of fibroblasts and were cell occulusive. In vivo, the BCSNF membranes were found to significantly improve the regeneration of a rat calvarial critical size defect in a 12 week healing period and showed better barrier function than commercially available collagen membranes with little soft tissue penetration through the membranes. Taken together, these data provide strong scientific evidence for use of BCSNF membranes in GBR applications.

In vitro and in vivo evaluations of a novel post-electrospinning treatment to improve the fibrous structure of chitosan membranes for guided bone regeneration.

Electrospun chitosan membranes have been investigated for guided bone regeneration but are susceptible to swelling, dissolution, and loss of biomimetic nanofiber structure due to residual acid salts. A novel process was investigated for acidic salt removal from chitosan electrospun in 70% trifluoroacetic acid (TFA) by treating with triethylamine (TEA)/acetone and di-tert-butyl dicarbonate (tBOC) instead of the common Na2CO3 treatment. TFA salt removal and nanofiber structure stabilization were confirmed by EDS, FTIR, 19F NMR and electron microscopy before and after soaking in water. Membrane degradation after 4 weeks in PBS with 100 µg ml-1 lysozyme and osteoblastic proliferation were similar between TEA/tBOC-treated and Na2CO3-treated membranes. A simulated surgical tear test using surgical tacks showed that the peak tensile tear strength of the TEA/tBOC-treated chitosan membranes (62.1 ± 1.9 N mm-1) was significantly greater than a commercial polylactic acid (PLA) membrane (13.4 ± 0.4 N mm-1), similar to one commercial collagen membrane (55.3 ± 7.5 N mm-1) but lower than another commercial collagen membrane (133.9 ± 21.5 N mm-1). Rat 8 mm critical-sized calvarial defects covered with TEA/tBOC-treated chitosan membranes prevented soft tissue infiltration and supported new bone growth (15.76 ± 10.28%) similar to a commercial collagen membrane (16.08 ± 10.69%) at 12 weeks based on microCT analyses. Hence our novel TEA/tBOC process significantly improved nanofiber structure and mechanical strengths of electrospun chitosan membranes as compared to Na2CO3 treated membranes, without affecting in vitro degradation or cytocompatibility, improved membrane mechanical properties to be greater than a commercial PLA membrane and to be in range of commercial collagen membranes and supported calvarial bone defect healing similar to collagen. Thus TEA/tBOC-treated chitosan membranes exhibit many characteristics and properties that strongly support their potential for use in guided bone regeneration.