Repurposing Human Osteoarthritic Cartilage as a Bone Graft Substitute in an Athymic Rat Posterolateral Spinal Fusion Model.

BACKGROUND: Spinal fusion involves both endochondral and intramembranous bone formation. We previously demonstrated that endochondral cartilage grafts that were derived from human osteoarthritic (OA) articular cartilage can be used as a bone graft in mouse models. We hypothesized that OA cartilage could also be recycled and repurposed as a bone graft substitute in a posterolateral lumbar spinal fusion model in athymic rats. METHODS: OA articular cartilage was obtained from the femoral resection of a healthy 60-year-old man undergoing elective total knee arthroplasty. The chondrocytes recovered from this tissue were dedifferentiated in monolayer tissue culture and then transitioned to culture conditions that promote chondrocyte hypertrophy. The resultant cell pellets were then used as bone graft substitute for single-level posterolateral spinal fusion in 5 athymic rats. Decortication alone was used as the control group. Spinal fusion was assessed with manual palpation, micro-computed tomography, and histologic analysis. RESULTS: In the experimental group, micro-computed tomography at 4 and 8 weeks demonstrated bilateral fusion in 4 of 5 animals and unilateral fusion in 1 animal. At 8 weeks, manual palpation and histologic analysis showed direct correlation with the radiographic findings. Animals undergoing decortication alone failed to generate any spinal fusion. The difference in the fusion rate between groups was statistically significant with respect to both unilateral fusion (P = .047) and bilateral fusion (P = .007). CONCLUSIONS: In the absence of additional surgically implanted bone graft, hypertrophic chondrocyte grafts are sufficient for generating single-level posterolateral lumbar fusion in athymic rats. CLINICAL RELEVANCE: This animal study demonstrates that cartilage harvested from OA knees can be used as a bone graft substitute. Commercially available cell-based bone grafts have previously only used mesenchymal stem cells or osteoblast precursor cells.

The Effects of Patient Obesity on Early Postoperative Complications After Shoulder Arthroscopy.

PURPOSE: To report the prevalence of obesity in shoulder arthroscopy, determine a body mass index (BMI) threshold most predictive of complication within 30 days, and evaluate obesity as an independent risk factor for medical and surgical complications. METHODS: Using the National Surgical Quality Improvement Program database, we reviewed all patients who underwent shoulder arthroscopy during 2011 to 2013. Receiver operating characteristic and Youden coefficient were calculated to find an optimal BMI cutoff to predict complications within 30 days of surgery. A case-control matched analysis was then performed by stratifying patient BMI by this cutoff and matching patients one to one according to age, sex, type of shoulder arthroscopy, American Society of Anesthesiology rating, surgical setting, and 8 comorbidities. Operating time, complications, and readmissions were also compared. RESULTS: Of the 15,589 patients who underwent shoulder arthroscopy, 6,684 (43%) were classified as obese when using the optimal cutoff point of BMI = 30 according to the Youden coefficient. Obese patients had a higher risk of superficial site infection than nonobese patients (0.3% vs 0.0%; odds ratio [OR]: 6.00; 95% confidence interval [CI], 1.3 to 26.8; P = .015). Obese patients did not have significantly increased risk for overall early postoperative complication (1.2% compared with nonobese 0.8%; OR: 1.54; 95% CI, 1.0 to 2.4), readmissions (OR: 0.85; 95% CI, 0.5 to 1.5), or increased operating time (P = .068). CONCLUSIONS: Up to 43% of patients undergoing shoulder arthroscopy can be classified as obese, but early perioperative complications are uncommon. Higher patient BMI is associated with increased risk of superficial site infection but not an overall risk for complication, readmission, or increased operating time. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Is Obesity a Risk Factor for Adverse Events After Knee Arthroscopy?

PURPOSE: To evaluate how body mass index (BMI) affects rates of 30-day complication, hospital readmissions, and mortality in patients undergoing knee arthroscopy. METHODS: Patients undergoing knee arthroscopy procedures between 2006 and 2013 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Patient demographics and preoperative risk factors including BMI were analyzed for postoperative complications within 30 days. Cochran-Armitage testing was performed to detect differences in complication rates across BMI categories according to World Health Organization classification. The independent risk of BMI was assessed using multivariate regression analysis. RESULTS: Of 41,919 patients with mean age 48 years undergoing knee arthroscopy, 20% were classified as normal weight (BMI 18.5 to 24), 35% overweight (BMI 25 to 29), 24% obese class I (BMI 30 to 34), 12% class II (BMI 35 to 40), and 9% class III (BMI ≥40). Risk of complication increased significantly with increasing BMI (normal: 1.5%, overweight: 1.6%, obese class I: 1.7%, obese class II: 1.8%, obese class III: 1.9%, P = .043). On multivariate analysis, there was no increased risk of postoperative complication directly attributed to patient BMI. Independent risk factors for medical and surgical complications after knee arthroscopy included American Society of Anesthesiologists (ASA) rating (class 4 v class 1 odds ratio [OR]: 5.39 [95% confidence interval: 3.11-9.33], P < .001), functional status for activities of daily living (dependent v independent OR: 2.13 [1.42, 3.31], P < .001), history of renal comorbidity (presence v absence OR: 5.10 [2.30, 11.29], P < .001), and previously experienced history of wound infection prior to current surgery (presence v absence OR: 4.91 [2.88, 8.39], P < .001). CONCLUSIONS: More than 40% of knee arthroscopy patients qualify as obese. Although univariate analysis suggests that obesity is associated with increased postoperative complications within 30 days of surgery, BMI alone does not predict complications. Independent predictors of complications include patients with high ASA classification, dependent functional status, renal comorbidities, and a recent history of wound infection. LEVEL OF EVIDENCE: Level IV, prognostic case series.

Promoting Endochondral Bone Repair Using Human Osteoarthritic Articular Chondrocytes.

INTRODUCTION: Current tissue engineering strategies to heal critical-size bone defects through direct bone formation are limited by incomplete integration of grafts with host bone and incomplete graft vascularization. An alternative strategy for bone regeneration is the use of cartilage grafts that form bone through endochondral ossification. Endochondral cartilages stimulate angiogenesis and are remodeled into bone, but are found in very small quantities in growth plates and healing fractures. We sought to develop engineered endochondral cartilage grafts using osteoarthritic (OA) articular chondrocytes as a cell source. Such chondrocytes often undergo hypertrophy, which is a characteristic of endochondral cartilages. MATERIALS AND METHODS: We compared the ability of unmodified human OA (hOA) cartilage and cartilage grafts formed in vitro from hOA chondrocytes to undergo endochondral ossification in mice. Scaffold-free engineered chondrocyte grafts were generated by pelleting chondrocytes, followed by culture with transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein 4. Samples derived from either primary or passaged chondrocytes were implanted subcutaneously into immunocompromised mice. Grafts derived from passaged chondrocytes from three patients were implanted into critical-size tibial defects in mice. Bone formation was assessed with histology after 4 weeks of implantation. The composition of tibial repair tissue was quantified with histomorphometry. RESULTS: Engineered cartilage grafts generated from passaged OA chondrocytes underwent endochondral ossification after implantation either subcutaneously or in bone. Cartilage grafts integrated with host bone at 15 out of 16 junctions. Grafts variably remodeled into woven bone, with the proportion of bony repair tissue in tibial defects ranging from 22% to 85% (average 48%). Bony repair tissue bridged the tibial defects in half of the animals. In contrast, unmodified OA cartilage and engineered grafts formed from primary chondrocytes did not undergo endochondral ossification in vivo. CONCLUSIONS: hOA chondrocytes can adopt an endochondral phenotype after passaging and TGF-ß superfamily treatment. Engineered endochondral cartilage grafts can integrate with host bone, undergo ossification, and heal critical-size long-bone defects in a mouse model. However, additional methods to further enhance ossification of these grafts are required before the clinical translation of this approach.

Muscle atrophy and fatty infiltration after an acute rotator cuff repair in a sheep model.

INTRODUCTION: rotator cuff tears (RCTs) are the most common tendon injury seen in orthopedic patients. Muscle atrophy and fatty infiltration of the muscle are crucial factors that dictate the outcome following rotator cuff surgery. Though less studied in humans, rotator cuff muscle fibrosis has been seen in animal models as well and may influence outcomes as well. The purpose of this study was to determine if the rotator cuff would develop muscle changes even in the setting of an acute repair in a sheep model. We hypothesized that fatty infiltration and fibrosis would be present even after an acute repair six months after initial surgery. METHODS: twelve female adult sheep underwent an acute rotator cuff tear and immediate repair on the right shoulder. The left shoulder served as a control and did not undergo a tear or a repair. Six months following acute rotator cuff repairs, sheep muscles were harvested to study atrophy, fatty infiltration, and fibrosis by histological analysis, western blotting, and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: the repair group demonstrated an increase expression of muscle atrophy, fatty infiltration, and fibrosis related genes. Significantly increased adipocytes, muscle fatty infiltration, and collagen deposition was observed in rotator cuff muscles in the tendon repair group compared to the control group. CONCLUSIONS: rotator cuff muscle undergoes degradation changes including fatty infiltration and fibrosis even after the tendons are repair immediately after rupture. LEVEL OF EVIDENCE: Basic Science Study.