Morphological Assessment of MACI Grafts in Patients with Revision Surgery and Total Joint Arthroplasty.

OBJECTIVE: To compare the histological and immunohistochemical characteristics of matrix-assisted chondrocyte implantation (MACI) grafts between patients with revision surgery and patients with total joint arthroplasty. METHODS: Biopsies of MACI grafts from patients with revision and total joint arthroplasty. The graft tissue characteristics and subchondral bone were examined by qualitative histology, ICRS (International Cartilage Repair Society) II scoring and semiquantitative immunohistochemistry using antibodies specific to type I and type II collagen. RESULTS: A total of 31 biopsies were available, 10 undergoing total knee arthroplasty (TKA) and 21 patients undergoing revision surgery. Patients in the clinically failed group were significantly older (46.3 years) than patients in the revision group (36.6 years) (P = 0.007). Histologically, the predominant tissue in both groups was of fibrocartilaginous nature, although a higher percentage of specimens in the revision group contained a hyaline-like repair tissue. The percentages of type I collagen (52.9% and 61.0%) and type II collagen (66.3% and 42.2%) were not significantly different between clinically failed and revised MACI, respectively. The talar dome contained the best and patella the worst repair tissue. Subchondral bone pathology was present in all clinically failed patients and consisted of bone marrow lesions, including edema, necrosis and fibrosis, intralesional osteophyte formation, subchondral bone plate elevation, intralesional osteophyte formation, subchondral bone cyst formation, or combinations thereof. CONCLUSIONS: MACI grafts in patients with revision and total joint arthroplasty were predominantly fibrocartilage in repair type, did not differ in composition and were histologically dissimilar to healthy cartilage. Clinically failed cases showed evidence of osteochondral unit failure, rather than merely cartilage repair tissue failure. The role of the subchondral bone in relation to pain and failure and the pathogenesis warrants further investigation.

The biology and clinical evidence of microfracture in hip preservation surgery.

The use of microfracture in hip arthroscopy is increasing dramatically. However, recent reports raise concerns not only about the lack of evidence to support the clinical use of microfracture, but also about the potential harm caused by violation of the subchondral bone plate. The biology and pathology of the microfracture technique were described based on observations in translational models and the clinical evidence for hip microfracture was reviewed systematically. The clinical outcomes in patients undergoing microfracture were the same as those not undergoing microfracture. However, the overall clinical evidence quality is poor in hips. This review identified only one study with Level III evidence, while most studies were Level IV. There were no randomized trials available for review. Repair tissue is primarily of fibrocartilaginous nature. Reconstitution of the subchondral bone is often incomplete and associated with poor quality repair tissue and faster degeneration. Subchondral bone cyst formation is associated with microfracture, likely secondary to subchondral bone plate disruption and a combination of pressurized synovial fluid and inflammatory mediators moving from the joint into the bone. There is a lack of clinical efficacy evidence for patients undergoing microfracture. There is evidence of bone cyst formation following microfracture in animal studies, which may accelerate joint degeneration. Bone cyst formation following microfracture has not been studied adequately in humans.

Treatment of Articular Cartilage Defects With Microfracture and Autologous Matrix-Induced Chondrogenesis Leads to Extensive Subchondral Bone Cyst Formation in a Sheep Model.

BACKGROUND: Microfracture and the autologous matrix-induced chondrogenesis (AMIC) technique are popular for the treatment of articular cartilage defects. However, breaching of the subchondral bone plate could compromise the subchondral bone structure. HYPOTHESIS: Microfracture and AMIC will cause deleterious effects on the subchondral bone structure. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 36 sheep received an 8-mm-diameter cartilage defect in the left medial femoral condyle. Control animals (n = 12) received no further treatment, and the rest received 5 microfracture holes either with a type I/III collagen scaffold implanted (n = 12; AMIC group) or without the collagen scaffold (n = 12; microfracture group). Macroscopic infill of defects, histology, and histomorphometry of the subchondral bone were performed at 13 and 26 weeks postoperatively, and micro-computed tomography (CT) was also performed at 26 weeks postoperatively. RESULTS: Microfracture and AMIC resulted in subchondral bone cyst formation in 5 of 12 (42%) and 11 of 12 (92%) specimens at 13 and 26 weeks, respectively. Subchondral bone changes induced by microfracture and AMIC were characterized by an increased percentage of bone volume, increased trabecular thickness, and a decreased trabecular separation, and extended beyond the area below the defect. High numbers of osteoclasts were observed at the cyst periphery, and all cysts communicated with the microfracture holes. Cartilage repair tissue was of poor quality and quantity at both time points and rarely reached the tidemark at 13 weeks. CONCLUSION: Microfracture technique caused bone cyst formation and induced severe pathology of the subchondral bone in a sheep model. CLINICAL RELEVANCE: The potential of microfracture technique to induce subchondral bone pathology should be considered.

Evaluation of an intramedullary bone stabilization system using a light-curable monomer in sheep.

Percutaneous intramedullary fixation may provide an ideal method for stabilization of bone fractures, while avoiding the need for large tissue dissections. Tibiae in 18 sheep were treated with an intramedullary photodynamic bone stabilization system (PBSS) that comprised a polyethylene terephthalate (Dacron) balloon filled with a monomer, cured with visible light in situ, and then harvested at 30, 90, or 180 days. In additional 40 sheep, a midshaft tibial osteotomy was performed and stabilized with external fixators or external fixators combined with the PBSS and evaluated at 8, 12, and 26 weeks. Healing and biocompatibility were evaluated by radiographic analysis, micro-computed tomography, and histopathology. In nonfractured sheep tibiae, PBSS implants conformably filled the medullary canal, while active cortical bone remodeling and apposition of new periosteal and/or endosteal bone was observed with no significant macroscopic or microscopic observations. Fractured sheep tibiae exhibited increased bone formation inside the osteotomy gap, with no significant difference when fixation was augmented by PBSS implants. Periosteal callus size gradually decreased over time and was similar in both treatment groups. No inhibition of endosteal bone remodeling or vascularization was observed with PBSS implants. Intramedullary application of a light-curable PBSS is a biocompatible, feasible method for fracture fixation.

The effects of multiple high-resolution peripheral quantitative computed tomography scans on bone healing in a rabbit radial bone defect model.

The use of in vivo high-resolution computed tomography (CT) scanners provides the unique opportunity for evaluating temporal progression in healing of bone defects. However, these in vivo scanners impose ionizing radiation that could affect the healing and morphology of the bone. The primary objective of this study was to determine the effects of in vivo scanning at 2-week intervals on bone healing of a critical sized radial defect in rabbits and to investigate the effect of this radiation protocol on bone marrow cell viability using clinically applicable radiation doses. Thirty male rabbits were randomized into three groups: two groups received a 15 mm defect in the left radius that was filled with an autologous bone graft (DEF-CT and DEF-SHAM), and one group acted as an intact control (INT-CT). The duration of the study was 6 weeks. DEF-CT and INT-CT had high-resolution CT scans performed at 2-week intervals. The total cumulative radiation dose was 81.6 mGy per animal. DEF-SHAM received sham CT scans at the same time points. In group DEF-CT, the bone volume (BV) in the defect increased significantly over time (p≤0.002, for all comparisons); the bone mineral density (BMD) in the defect decreased over time and was significantly lower at weeks 4 and 6 than at weeks 0 and 2 (p<0.001, for all comparisons). In group INT-CT, BV and BMD did not change over time (p=1, for all comparison). The BV (p=0.50) and the BMD (p=0.37) in the defect as measured by microCT scan during ex vivo analysis was not significantly different between DEF-CT and DEF-SHAM. Similarly, histomorphometry showed no significant difference in the total bone area (p=0.22) and percentage bone within the defect (p=0.24) between these groups. Bone marrow analysis of the left (radiated) and right (non-radiated) radius of the INT-CT group via a Colony Forming Units (CFU) assay demonstrated an average of 25.3 and 28.5 colonies for radiated and non-radiated radii, respectively (p=0.72). In conclusion, there was no significant difference in bone healing between radiated and non-radiated radius defects in rabbits. This is an important finding as it demonstrates that serial in vivo high resolution-CT imaging can not only provide accurate tissue regeneration data, but it can also be used to reduce the number of temporal cohorts within an experimental design.

The use of Reamer Irrigator Aspirator (RIA) autograft harvest in the treatment of critical-sized iliac wing defects in sheep: investigation of dexamethasone and beta-tricalcium phosphate augmentation.

Bone grafts are commonly used for the treatment of segmental bone defects and fracture non-unions. Recently, osseous particles obtained during intermedullary canal reaming (using a Reamer-Irrigator-Aspirator (RIA) device) have been evaluated as graft material during in vitro and clinical studies. The aim of this study was to evaluate and quantify new bone formation after implantation of bone graft material obtained after reaming of the tibia in a bilateral critical-sized iliac wing defect in sheep and to investigate the effect of the augmentation of this graft. A reamer bone graft alone, or after short term incubation in a dexamethasone enriched solution, and a reamer graft collected using beta-tricalcium phosphate (ß-TCP) granules in the filter of the RIA collection device were compared to autologous iliac wing graft. In addition, reamer graft was combined with the cellular fraction collected from the irrigation fluid with and without short-term incubation in a dexamethasone enriched solution. It was hypothesized that the amount of physical bone in the reamer bone graft groups would be higher than the amount in the autologous iliac wing graft group and that augmentation of a reamer bone graft would increase bone formation. Three months after implantation, the amount of new bone formation (as percentage of the total defect volume) in the defects was evaluated ex-vivo by means of micro-CT and histomorphometry. The mean amount of bone in the autologous iliac wing graft group was 17.7% and 16.8% for micro-CT and histomorphometry, respectively. The mean amount of bone in all reamer graft groups ranged between 20.4-29.2% (micro-CT) and 17.0-25.4% (histomorphometry). Reamer graft collected using ß-TCP granules (29.2±1.7%) in the filter produced a significantly higher amount of bone in comparison to an autologous iliac wing graft evaluated by micro-CT. RIA bone grafts added a small increase in bone volume to the 3month graft volume in this preclinical sheep model. The current model does not support the use of short-term high concentration dexamethasone for augmentation of a graft volume. If avoidance of an iliac wing graft is desirable, or a reaming procedure is required, then a RIA graft or RIA graft plus ß-TCP granules are as good as the current gold standard for this model.

Submandibular lymph node abscess caused by Actinomyces denticolens in a horse in Ontario.

This is the first report of the isolation of Actinomyces denticolens, an opportunistic pathogen, from a draining submandibular lymph node abscess in a horse in Ontario. Due to the similarity of the clinical signs with strangles, this pathogen should be included in the differential diagnosis of submandibular lymphadenopathy in the horse.