No abstract

Acellular hydroxyapatite (HA) reinforced collagen scaffolds were previously reported to induce angiogenesis and osteogenesis after ectopic implantation but the effect of the HA volume fraction was not investigated. Therefore, the objective of this study was to investigate the effect of HA volume fraction on in vivo angiogenesis and osteogenesis in acellular collagen scaffolds containing 0, 20, and 40 vol % HA after subcutaneous ectopic implantation for up to 12 weeks in mice. Endogenous cell populations were able to completely and uniformly infiltrate the entire scaffold within 6 weeks independent of the HA content, but the cell density was increased in scaffolds containing HA versus collagen alone. Angiogenesis, remodeling of the original scaffold matrix, mineralization, and osteogenic gene expression were evident in scaffolds containing HA, but were not observed in collagen scaffolds. Moreover, HA promoted a dose-dependent increase in measured vascular density, cell density, matrix deposition, and mineralization. Therefore, the results of this study suggest that HA promoted the recruitment and differentiation of endogenous cell populations to support angiogenic and osteogenic activity in collagen scaffolds after subcutaneous ectopic implantation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2178-2188, 2016.

Histology and backscatter scanning electron microscopy (bSEM) are the current gold standard methods for quantifying bone-implant contact (BIC), but are inherently destructive. Microcomputed tomography (μCT) is a non-destructive alternative, but attempts to validate μCT-based assessment of BIC in animal models have produced conflicting results. We previously showed in a rat model using a 1.5 mm diameter titanium implant that the extent of the metal-induced artefact precluded accurate measurement of bone sufficiently close to the interface to assess BIC. Recently introduced commercial laboratory μCT scanners have smaller voxels and improved imaging capabilities, possibly overcoming this limitation. The goals of the present study were to establish an approach for optimizing μCT imaging parameters and to validate μCT-based assessment of BIC. In an empirical parametric study using a 1.5 mm diameter titanium implant, we determined 90 kVp, 88 µA, 1.5 μm isotropic voxel size, 1600 projections/180°, and 750 ms integration time to be optimal. Using specimens from an in vivo rat experiment, we found significant correlations between bSEM and μCT for BIC with the manufacturer's automated analysis routine (r = 0.716, p = 0.003) or a line-intercept method (r = 0.797, p = 0.010). Thus, this newer generation scanner's improved imaging capability reduced the extent of the metal-induced artefact zone enough to permit assessment of BIC. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:979-986, 2018.

No abstract

Biomarkers are of interest to identify patients at risk for peri‐implant osteolysis and aseptic loosening. We used a rat model of particle‐induced peri‐implant osteolysis to investigate if early changes in biomarkers were associated with subsequent implant fixation strength. Implants were placed in rat femora, which were then challenged with intra‐articular knee injections of either clean polyethylene, lipopolysaccharide‐doped polyethylene, or cobalt‐chromium alloy particles, with particle‐free vehicle serving as control (n ≥ 8 per group). Rats were weighed weekly, blood was collected at weeks 0, 3, 5, and 6, and locomotor behavior was assessed 4 days before study conclusion. Rats were euthanized 6 weeks post surgery. Week 6 serum was analyzed for five bone remodeling markers, while longitudinal serum was assessed for osteocalcin. Bone‐implant contact, peri‐implant trabecular architecture, and implant fixation strength were measured. Rats challenged with cobalt‐chromium particles had a significant reduction in implant fixation strength compared with the vehicle‐control group (P = .034). This group also had elevated serum osteocalcin (P = .005), depressed weight gain (P = .001) and less frequent rearing behavior (P = .029). Regardless of group, change in serum osteocalcin at week 3 (r = −.368; P = .046), change in weight at week 2 (r = .586; P < .001), as well as weight change at all other time intervals were associated with fixation strength. The finding that early alterations in serum osteocalcin and body weight were predictive of subsequent implant fixation strength supports continued investigation of biomarkers for early detection of peri‐implant osteolysis and implant loosening. Further, change in biomarker levels was found to be more indicative of implant fixation status than any single measurement.