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Background: In this study, we investigate the in vitro and in vivo chondrogenic capacity of a novel photopolymerizable cartilage mimetic hydrogel, enhanced with extracellular matrix analogs, for cartilage regeneration., Purpose: To (1) determine whether mesenchymal stem cells (MSCs) embedded in a novel cartilage mimetic hydrogel support in vitro chondrogenesis, (2) demonstrate that the proposed hydrogel can be delivered in situ in a critical chondral defect in a rabbit model, and (3) determine whether the hydrogel with or without MSCs supports in vivo chondrogenesis in a critical chondral defect., Study Design: Controlled laboratory study., Methods: Rabbit bone marrow-derived MSCs were isolated, expanded, encapsulated in the hydrogel, and cultured in chondrogenic differentiation medium for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6, and 9. Chondrogenic differentiation was investigated via quantitative polymerase reaction, safranin-O staining, and immunofluorescence. In vivo, a 3 mm-wide × 2-mm-deep chondral defect was created bilaterally on the knee trochlea of 10 rabbits. Each animal had 1 defect randomly assigned to be treated with hydrogel with or without MSCs, and the contralateral knee was left untreated. Hence, each rabbit served as its own matched control. Three groups were established: group A, hydrogel (n = 5); group B, hydrogel with MSCs (n = 5); and group C, control (n = 10). Repair tissue was evaluated at 6 months after intervention., Results: In vitro, chondrogenesis and the degradable behavior of the hydrogel by MSCs were confirmed. In vivo, the hydrogel could be delivered intraoperatively in a sterile manner. Overall, the hydrogel group had the highest scores on the modified O'Driscoll scoring system (group A, 17.4 ± 4.7; group B, 13 ± 3; group C, 16.7 ± 2.9) ( P = .11) and showed higher safranin-O staining (group A, 49.4% ± 20%; group B, 25.8% ± 16.4%; group C, 36.9% ± 25.2%) ( P = .27), although significance was not detected for either parameter., Conclusion: This study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a small animal model. In vitro chondrogenesis was evident when MSCs were encapsulated in the hydrogel., Clinical Relevance: Cartilage mimetic hydrogel may offer a tissue engineering approach for the treatment of osteochondral lesions.

Background: Limited information in basic science and clinical trials exists to determine if ligament healing may be accelerated with the use of biological adjuvants, such as platelet-rich plasma (PRP). However, there has been widespread acceptance of PRP for use in clinical practice, despite an inadequate understanding of its biological mechanism of action., Purpose: To determine whether a single dose of PRP could accelerate ligament healing and correspondingly improve histological characteristics and biomechanical properties when injected immediately postoperatively into the injured medial collateral ligament (MCL) of New Zealand White rabbits., Study Design: Controlled laboratory study., Methods: Eighty skeletally mature New Zealand White rabbits (160 knees) were used. The MCL was torn midbody to simulate a grade 3 tear. After an acute injury of the MCL, the administration of autologous PRP at 3 different platelet concentrations (0 million/uL, platelet-poor plasma [PPP]; 0.6 million/uL, 2 times the baseline [2× PRP]; and 1.2 million/uL, 4 times the baseline [4× PRP]) was performed and compared with a saline injection control in the contralateral knee. Histological analysis and a biomechanical endpoint characterization were utilized to assess ligamentous healing and compare it to a sham surgery group., Results: The PPP ( P = .001) and 4× PRP ( P = .002) groups had a significantly lower collagen subscore than the sham surgery group. No other differences were observed among the treatment groups, including the vascularity subscore and overall ligament tissue maturity index score. Compared with saline-injected contralateral knees, the maximum load for PPP and 2× PRP was not significantly different ( P = .788 and .325, respectively). The maximum load and stiffness for knees treated with 4× PRP were significantly less than for the saline-treated contralateral knees ( P = .006 and .001, respectively)., Conclusion: One single dose of PPP or 2× PRP at the time of injury did not improve ligament healing. In addition, 4× PRP negatively affected ligament strength and histological characteristics at 6 weeks after the injury., Clinical Relevance: The current practice of treating knee ligament injuries with PRP may not improve healing at low doses of PRP. The decreased mechanical properties and histological appearance of the torn MCL suggest that high doses of PRP decrease the quality of repair tissue. Further in vivo studies are necessary to determine the dosing and timing of PRP administration after a ligament injury before the widespread use of PRP to treat ligament injuries is recommended.

Background: Chondral defects may lead to degradative changes in the surrounding cartilage, predisposing patients to developing osteoarthritis., Purpose: To quantify changes in the biomechanical and biochemical properties of the articular cartilage adjacent to chondral defects after experimental defect repair., Study Design: Controlled laboratory study., Methods: Specimens were harvested from tissue within (lesion), immediately adjacent to, and at a distance from (remote area) a full-thickness cartilage defect 8 months after cartilage repair with genetically modified chondrocytes expressing insulin-like growth factor-I or unmodified, control chondrocytes. Biomechanical properties, including instantaneous Young's and equilibrium aggregate moduli, were determined by confined compression testing. Biochemical properties, such as water and proteoglycan content, were also measured., Results: The instantaneous Young's modulus, equilibrium modulus, and proteoglycan content increased, whereas water content decreased with increasing distance from the repaired lesion. The instantaneous Young's and equilibrium moduli of the adjacent articular cartilage were 80% and 50% that of remote area samples, respectively, whereas water content increased 0.9% and proteoglycan content was decreased by 35%. No significant changes in biomechanical and biochemical properties were found either in the lesion tissue or in adjacent cartilage with genetic modification of the chondrocytes., Conclusion: Articular cartilage adjacent to repaired chondral defects showed significant remodeling 8 months after chondral defect repair, regardless of whether genetically modified or unmodified cells were implanted., Clinical Relevance: Changes in the biochemical and biomechanical properties of articular cartilage adjacent to repaired chondral defects may represent remodeling as part of an adaptive process or degeneration secondary to an altered distribution of joint forces. Quantification of these changes could provide important parameters for assessing progress after operative chondral defect repair.