In vivo evaluation of 3D printed polycaprolactone composite scaffold and recombinant human bone morphogenetic protein-2 for vertical bone augmentation with simultaneous implant placement on rabbit calvaria.

This study evaluated 3D printed polycaprolactone (PCL) composite scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2), loaded either onto a PCL composite scaffold or implant surface, for vertical bone augmentation with implant placement. Three-dimensional printed PCL frames were filled with powdered PCL, hydroxyapatite, and ß-tricalcium phosphate. RhBMP-2 was loaded to the PCL composite scaffolds and implant surfaces, and rhBMP-2 release was quantified for 21 days. Experimental implants were placed bilaterally on 20 rabbit calvaria, and the PCL composite scaffolds were vertically augmented. The randomly allocated experimental groups were divided by carrier and rhBMP-2 dosage as no rhBMP-2 (control), 5 µg rhBMP-2 loaded to PCL composite (Scaffold/rhBMP-2[5 µg]), 5 µg rhBMP-2 loaded to implant (Implant/rhBMP-2[5 µg]), 30 µg rhBMP-2 loaded to PCL composite (Scaffold/rhBMP-2[30 µg]), and 30 µg rhBMP-2 loaded to implant (Implant/rhBMP-2[30 µg]). Histologic and histometric analyses were conducted after 8 weeks. In both scaffold-loading and implant-loading, rhBMP-2 released initially rapidly, then slowly and constantly. Released rhBMP-2 totaled 23.02 ± 1.03% and 24.69 ± 1.14% in the scaffold-loaded and implant-loaded groups, respectively. There were no significant differences in histologic bone-implant contact (%). Peri-implant bone density (%) was significantly higher in the Scaffold/rhBMP-2(30 µg) and Implant/rhBMP-2(30 µg) groups. Total bone density (%) was not significantly different between the Scaffold/rhBMP-2(5 µg), Implant/rhBMP-2(5 µg), and control groups, or between the Scaffold/rhBMP-2(30 µg) and Implant/rhBMP-2(30 µg) groups, but was significantly higher in the Scaffold/rhBMP-2(30 µg) and Implant/rhBMP-2(30 µg) groups than in the controls. Three-dimensional printed PCL composite scaffold with rhBMP-2 produced vertical osteogenesis and osseointegration, regardless of rhBMP-2 loading to the PCL composite scaffold or implant surface.

Enhancement of Bone Ingrowth into a Porous Titanium Structure to Improve Osseointegration of Dental Implants: A Pilot Study in the Canine Model.

A porous titanium structure was suggested to improve implant stability in the early healing period or in poor bone quality. This study investigated the effect of a porous structure on the osseointegration of dental implants. A total of 28 implants (14 implants in each group) were placed in the posterior mandibles of four beagle dogs at 3 months after extraction. The control group included machined surface implants with an external implant-abutment connection, whereas test group implants had a porous titanium structure added to the apical portion. Resonance frequency analysis (RFA); removal torque values (RTV); and surface topographic and histometric parameters including bone-to-implant contact length and ratio, inter-thread bone area and ratio in total, and the coronal and apical parts of the implants were measured after 4 weeks of healing. RTV showed a significant difference between the groups after 4 weeks of healing (p = 0.032), whereas no difference was observed in RFA. In the test group, surface topography showed bone tissue integrated into the porous structures. In the apical part of the test group, all the histometric parameters exhibited significant increases compared to the control group. Within the limitations of this study, enhanced bone growth into the porous structure was achieved, which consequently improved osseointegration of the implant.

Surface engineering of titanium alloy using metal-polyphenol network coating with magnesium ions for improved osseointegration.

Although titanium-based implants are widely used in orthopedic and dental clinics, improved osseointegration at the bone-implant interface is still required. In this study, we developed a titanium alloy (Ti-6Al-4V, Ti) coated with epigallocatechin gallate (EGCG) and magnesium ions (Mg2+) in a metal-polyphenol network (MPN) formation. Specifically, Ti discs were coated with EGCG in MgCl2 by controlling their concentrations and pH, with the amount of coating increasing with the coating time. An in vitro culture of human adipose-derived stem cells (hADSCs) on the EGCG-Mg2+-coated Ti showed significantly enhanced ALP activity and mRNA expression of osteogenic markers. In addition, the EGCG-Mg2+-coated Ti enhanced the mineralization of hADSCs, significantly increasing the calcium content (22.2 ± 5.0 µg) compared with cells grown on Ti (13.5 ± 0.3 µg). Treatment with 2-APB, an inhibitor of Mg2+ signaling, confirmed that the enhancement of osteogenic differentiation in the hADSCs was caused by the synergistic influence of EGCG and Mg2+. The EGCG-Mg2+ coating significantly reduced the osteoclastic maturation of Raw264.7 cells, reducing tartrate-resistant acid phosphatase activity (5.4 ± 0.4) compared with that of cells grown on Ti (1.0 ± 0.5). When we placed Ti implants onto rabbit tibias, the bone-implant contact (%) was greater on the EGCG-Mg2+-coated Ti implants (8.1 ± 4.3) than on the uncoated implants (4.4 ± 2.0). Therefore, our MPN coating could be a reliable surface modification for orthopedic implants to enable the delivery of an osteoinductive metal ion (Mg2+) with the synergistic benefits of a polyphenol (EGCG).

Comparative preclinical assessment of the use of dehydrated human amnion/chorion membrane to repair perforated sinus membranes.

PURPOSE: The aim of this study was to evaluate the use of dehydrated human amnion/chorion membrane (dHACM) to repair perforated sinus membranes in rabbits. METHODS: Bilateral surgical windows (7.5-mm diameter) were prepared on the nasal bones of 14 rabbits. Standardized circular perforations (5-mm diameter) were made in the sinus membrane by manipulating implant twist drills. The perforated sinus membranes were repaired using dHACM or a resorbable collagen membrane (CM). The negative control (NC) group did not undergo perforated sinus membrane repair, while the positive control (PC) group underwent sinus augmentation without perforations. The same amount of deproteinized porcine bone mineral was grafted in all 4 groups. After 6 weeks, micro-computed tomography (micro-CT) and histomorphometric evaluations were conducted. RESULTS: The micro-CT analysis revealed that the total augmented volume was not significantly different among the groups. In the dHACM group, newly formed bone filled the augmented area with remaining biomaterials; however, non-ciliated flat epithelium and inflammatory cells were observed on the healed sinus membrane. Histometric analysis showed that the percentage of newly formed bone area in the dHACM group did not differ significantly from that in the CM group. The dHACM group showed a significantly higher percentage of newly formed bone area than the NC group, but there was no significant difference between the dHACM and PC groups. CONCLUSIONS: dHACM could be a feasible solution for repairing sinus membrane perforations that occur during sinus floor augmentation.

Effect of microthreads on coronal bone healing of narrow-diameter implants with reverse-tapered design in beagle dogs.

OBJECTIVES: The objective of this study was to investigate the effect of microthreads on the coronal bone healing of narrow-diameter implants with reverse-tapered design. MATERIAL AND METHODS: A total of 52 implants were classified into two groups according to presence or absence of coronal microthreads, the reverse-tapered narrow-diameter implant (RTN) group, and the reverse-tapered narrow-diameter implant with microthreads (RTNM) group. The implants were installed in split-mouth design in the edentulous mandible of six dogs. Three animals were sacrificed at 4 weeks and three at 8 weeks. Resonance frequency analysis, bone measurement using microcomputed tomography (micro-CT), removal torque test, and histometric analysis were performed. RESULTS: No significant differences in implant stability quotient value were observed between the groups at baseline, 4 weeks, or 8 weeks. Bone measurement using micro-CT showed that bone-implant contact volume (BICV) and bone-implant contact volume ratio (BICVR) in the coronal part of RTNM were statistically higher than those in RTN at 4 and 8 weeks. Histometric analysis showed statistically higher bone-implant contact length (BICL) in the coronal part of RTNM than in RTN at 4 weeks; however, bone-implant contact ratio (BICR) was not significantly different between the groups. At 8 weeks, the BICL and BICR did not differ significantly between the groups. Removal torque test showed no significant differences between the groups at 4 and 8 weeks. CONCLUSIONS: The microthreads might facilitate more coronal bone-implant contact due to increased surface areas at an early healing phase; however, they did not significantly affect coronal bone healing at 8 weeks.

Evaluation of a Reverse-Tapered Design on the Osseointegration of Narrow-Diameter Implants in Beagle Dogs: A Pilot Study.

PURPOSE: The purpose of this study was to evaluate a reverse-tapered design on the osseointegration of narrow-diameter implants in comparison with a conventional tapered design in beagle dogs. MATERIALS AND METHODS: All mandibular premolars and first molars were extracted bilaterally in four beagle dogs. Three months later, three kinds of implants were placed in both quadrants of the mandible: tapered narrow-diameter implants processed by cold working (TNC; n = 8), reverse-tapered narrow-diameter implants (RTN; n = 8), and reverse-tapered narrow-diameter implants processed by cold working (RTNC; n = 8). The animals were sacrificed at 4 weeks. Implant stability quotient (ISQ) values were measured at the time of implant placement and sacrifice. Histomorphometric analysis was performed. RESULTS: The baseline ISQ values were significantly lower in the RTN (56.0 ± 11.6) and RTNC (57.2 ± 9.8) than in the TNC (68.0 ± 5.4; P = .021). At 4 weeks, the TNC (69.9 ± 5.1) exhibited significantly higher ISQ values compared with the RTNC (61.6 ± 4.1; P = .024). Histologic analysis in the RTN and RTNC revealed osseointegration without any signs of inflammation; however, unresolved coronal gap or dehiscence was also observed. The total bone-to-implant contact ratios (BIC) in TNC, RTN, and RTNC were 55.1% ± 11.5%, 47.8% ± 19.1%, and 60.2% ± 15.3%, respectively, and no significant differences were shown among them. The BIC for the coronal part in each group was 51.1% ± 29.4%, 28.8% ± 33.8%, and 23.9% ± 23.3%, respectively, and the differences were not significant. In the threaded part, TNC, RTN, and RTNC showed a BIC of 56.3% ± 9.6%, 50.7% ± 18.3%, and 65.3% ± 15.6%, respectively. There was no significant difference among them. CONCLUSION: The reverse-tapered design on narrow-diameter implants showed a lower initial stability than the conventional tapered design; however, there was equivalent osseointegration in an early healing phase.

Comparison of collagen membrane and bone substitute as a carrier for rhBMP-2 in lateral onlay graft.

OBJECTIVES: To evaluate the bone regenerative effect of bioresorbable collagen membrane (CM) as a carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2) when performing lateral onlay grafts using bovine hydroxyapatite incorporated with collagen matrix (BHC) in combination with CM in dogs. MATERIAL AND METHODS: A guided bone regeneration (GBR) was performed at the buccal aspect of edentulous maxillary alveolar ridges in dogs (n = 5): (1) BHC group, in which rhBMP-2-loaded BHC was covered by a CM, and (2) CM group, in which BHC was covered by an rhBMP-2-loaded CM. A histologic and histometric analysis was performed after 8 weeks of healing. RESULTS: Both the BHC and CM groups exhibited substantial newly formed bone (NB). More NB was found in the CM group than in the BHC group without statistical significance. Most of the NB was in direct contact with the residual bone substitute in the BHC group, whereas the projections and islands of NB were observed in the spaces between the residual bone substitute clusters in the CM group. The bone-to-residual bone substitute contact ratio was significantly lower in the CM group than in the BHC group (P = 0.043). CONCLUSIONS: Within the limitations of this study, it can be concluded that rhBMP-2-loaded CM performed lateral onlay grafts as effectively as rhBMP-2-loaded BHC while showing less bone-residual bone substitute contact ratio in dogs. The loading of CMs with rhBMP-2 might therefore be a recommendable treatment option for facilitating lateral onlay graft combined with rhBMP-2.

The biological effect of cyanoacrylate-combined calcium phosphate in rabbit calvarial defects.

PURPOSE: The purpose of this study was to determine the biological effects of cyanoacrylate-combined calcium phosphate (CCP), in particular its potential to act as a physical barrier - functioning like a membrane - in rabbit calvarial defects. METHODS: In each animal, four circular calvarial defects with a diameter of 8 mm were prepared and then filled with either nothing (control group) or one of three different experimental materials. In the experimental conditions, they were filled with CCP alone (CCP group), filled with biphasic calcium phosphate (BCP) and then covered with an absorbable collagen sponge (ACS; BCP/ACS group), or filled with BCP and then covered by CCP (BCP/CCP group). RESULTS: After 4 and 8 weeks of healing, new bone formation appeared to be lower in the CCP group than in the control group, but the difference was not statistically significant. In both the CCP and BCP/CCP groups, inflammatory cells could be seen after 4 and 8 weeks of healing. CONCLUSIONS: Within the limits of this study, CCP exhibited limited osteoconductivity in rabbit calvarial defects and was histologically associated with the presence of inflammatory cells. However, CCP demonstrated its ability to stabilize graft particles and its potential as an effective defect filler in bone augmentation, if the biocompatibility and osteoconductivity of CCP were improved.