Preparation, physicochemical characterization, and in vitro and in vivo osteogenic evaluation of a bioresorbable, moldable, hydroxyapatite/poly(caprolactone-co-lactide) bone substitute.

Use of bioresorbable artificial bone substitutes is anticipated for bone augmentation in dental implant surgery because they are relatively economical and uniform in quality compared to heterogeneous bone. In this study, a new shapable, rubbery, bioresorbable bone substitute was developed. The material was prepared by ultrasonically dispersing hydroxyapatite (HA) particles throughout a poly (caprolactone-co-lactide) (PCLLA) rubbery matrix. Physiochemical properties of the bone substitute including its composition, deformability, anti-collapse ability, degradation behavior, and in vitro and in vivo osteogenic ability were evaluated. Results revealed that HA/PCLLA, which consists of homogeneously dispersed HA particles and a rubbery matrix composed of PCLLA, possesses a deformable capacity. The result of the mass retention rate of the material indicated an excellent durability in an aqueous environment. Further, the effects of HA/PCLLA on cell functions and bone-regenerated performance were evaluated in vitro and in vivo. The results showed that HA/PCLLA had enhanced proliferative capacity, and ability to undergo osteogenic differentiation and mineralization in vitro. It was also found that HA/PCLLA had an appropriate degradation rate to induce consecutive new bone formation without collapse at the early stage in vivo, as well as the ability to maintain the contour of the bone-grafting area, which is comparable to the deproteinized bovine bone mineral. These results indicated that HA/PCLLA is a promising bioresorbable bone substitute with properties that meet clinical requirements, including deformability, resistance to collapse in an aqueous environment, appropriate early-stage degradation rate, biocompatibility, osteogenic bioactivity and the capacity to regenerate bone tissue with favorable contour.

Efficacy of a mineralized collagen bone-grafting material for peri-implant bone defect reconstruction in mini pigs.

The mechanism of the mineralization process induced by natural mineralized collagen (MC) has been investigated for decades. The purpose of this study was to investigate the efficacy of self-assembled MC for peri-implant bone defect reconstruction in a mini pig. A standardized peri-implant bone defect model was created using 14 mini pig mandibles. Two materials were evaluated, i.e. a mixture of hydroxyapatite and collagen (Type A, TA), and self-assembled MC (Type B, TB). Bio-Oss (BO) and untreated (blank control, BC) groups were used as controls. After 3- and 6-month healing periods, the mini pigs were sacrificed for histomorphometric and microcomputed tomography analysis. After 3 months of healing, the average alveolar ridge height was 3.27 ± 1.57 mm for group TA, 3.28 ± 2.02 mm for group TB and 3.37 ± 1.09 mm for group BO, while group BC showed the lowest height of 2.68 ± 0.47 mm. After 6 months of healing, the average alveolar ridge height was 2.64 ± 1.13 mm for group TA, 4.31 ± 1.80 mm for group TB and 3.87 ± 1.38 mm for group BO, while group BC showed the lowest height of 2.48 ± 1.80 mm. The experimental groups and control group showed similar bone volume density, bone complexity and histological reaction. The self-assembled MC (Type B) stimulated new bone formation in the reconstruction of deficient alveolar ridges around the dental implant; it also displayed excellent clinical operability compared with bone grafts without collagen.

Biomechanical and histological evaluation of the osseointegration capacity of two types of zirconia implant.

The purpose of this study was to evaluate the biomechanical and histological behavior of a ceria-stabilized zirconia-alumina nanocomposite (NanoZr) in comparison with that of 3 mol% yttria-stabilized tetragonal zirconia polycrystalline (3Y-TZP) in Sprague Dawley rats. Cylindrical NanoZr and 3Y-TZP implants (diameter 1 mm, length 2 mm) were used. Implant-surface morphology and surface roughness were determined by scanning white-light interferometry and scanning electron microscopy, respectively. The cylindrical zirconia implants were placed at the distal edge of the femur of Sprague Dawley rats. At weeks 2, 4, and 8, the interfacial shear strength between implant and bone was measured by push-in test. Histological analysis was performed using hard-tissue sections. Bone-implant contact (BIC), the thickness of new bone around the implant within the bone marrow area, and osteoclast numbers were evaluated. The average surface roughness of 3Y-TZP (Sa 0.788 µm) was significantly higher than that of NanoZr (Sa 0.559 µm). The shear strengths of 3Y-TZP and NanoZr were similar at 2 weeks, but at 4 and 8 weeks the shear strength of NanoZr was higher than that of 3Y-TZP. The average BIC values within the bone marrow area for 3Y-TZP and NanoZr were 25.26% and 31.51% at 2 weeks, 46.78% and 38% at 4 weeks, and 47.88% and 56.81% at 8 weeks, respectively. The average BIC values within the cortical area were 38.86% and 58.42% at 2 weeks, 66.82% and 57.74% at 4 weeks, and 79.91% and 78.97% at 8 weeks, respectively. The mean BIC value did not differ significantly between the two zirconia materials at any time point. The NanoZr implants were biocompatible, capable of establishing close BIC, and may be preferred for metal-free dental implants.

Galactosylated reversible hydrogels as scaffold for HepG2 spheroid generation.

Various galactosylated scaffolds have been developed for hepatocyte culture because galactose ligands help maintain cell viability, facilitate the formation of multicellular spheroids and help maintain a high level of liver-specific functions. However, it is difficult to harvest the cell spheroids generated inside the three-dimensional scaffolds for their further biological analysis and applications. Here we developed a new galactosylated hydrogel scaffold which solidifies in situ upon heating to physiological temperature, but liquefies again upon cooling back to room temperature. The new scaffold is composed of poly(N-isopropylacrylamide) (PNIPAM) microgel and poly(ethylene glycol) (PEG). Because of the thermosensitivity of PNIPAM microgel, the mixed dispersions gel upon heating and liquefy upon cooling. PEG was added to reduce the shrinkage of the gels. Part of the PNIPAM microgel was replaced with a galactosylated one to provide a series of blend gels with various galactose ligand contents. HepG2 cells, a human hepatocarcinoma cell line, were encapsulated in the in situ-formed gels. As expected, the cell viability increases with increasing content of galactose ligands. In addition, compact multicellular spheroids were obtained in gels containing galactose ligands, while loose spheroids formed in gel without galactose ligands. The cells cultured in galactose-containing gels also exhibit a higher level of liver-specific functions, in terms of both albumin secretion and urea synthesis, than those cultured in gel without these ligands. The new galactosylated scaffold not only promotes the formation of hepatocyte spheroids, but also allows for their harvest. By cooling back to room temperature to liquefy the gel, the hepatocyte spheroids can be facilely harvested from the scaffold. The reversible galactosylated scaffold developed here may be used for large scale fabrication of hepatocyte spheroids.