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Background: Owing to the disappointing regenerative ability of osteochondral tissue, without treatment an osteochondral defect would progress to osteoarthritis. This situation motivates the need for new strategies to enhance the regeneration of osteochondral defects. Purpose: To develop a tissue-engineering scaffold by tethering bone morphogenetic protein 2 (BMP2) and transforming growth factor beta 3 (TGFβ3) in a layer-specific manner on a slotted decellularized osteochondral matrix (SDOM) and to evaluate the efficacy of this scaffold for osteochondral regeneration. Study Design: Controlled laboratory study. Methods: Normal osteochondral tissue from the rabbit patellofemoral groove was sectioned into a slot shape and decellularized for fabricating an SDOM. The collagen-binding domain (CBD) was fused into the N-terminus of BMP2 or TGFβ3 to synthesize 2 recombinant growth factors (GFs) (CBD-BMP2 or CBD-TGFβ3), which were tethered to the bone layer and cartilage layer, respectively, of the SDOM to prepare a tissue-engineering scaffold (namely, CBD-GFs/SDOM). After examining the influence of the CBD-GFs/SDOM on the viability and layer-specific differentiation of bone marrow mesenchymal stem cells in vitro, we determined the regeneration potential of the CBD-GFs/SDOM on osteochondral regeneration in a rabbit model. A total of 72 New Zealand White rabbits with a cylindrical osteochondral defect in the patellofemoral groove were randomly assigned to 3 groups: defect only (control [CTL] group), defect patched with an SDOM (SDOM group), and defect patched with the CBD-GFs/SDOM (CBD-GFs/SDOM group). At 6 or 12 weeks postoperatively, the rabbits were euthanized to harvest the knee joint, which was then evaluated via gross observation, micro–computed tomography, histological staining, and mechanical testing. Results: In vitro, the CBD-GFs/SDOM was noncytotoxic, showed high biomimetics with normal osteochondral tissue, was suitable for cell adhesion and growth, and had good layer-specific ability in inducing stem cell differentiation. Macroscopic images showed that the CBD-GFs/SDOM group had significantly better osteochondral regeneration than the CTL and SDOM groups had. Micro–computed tomography demonstrated that much more bony tissue was formed at the defect sites in the CBD-GFs/SDOM group compared with the defect sites in the CTL or SDOM group. Histological analysis showed that the CBD-GFs/SDOM group had a significant enhancement in osteochondral regeneration at 6 and 12 weeks postoperatively in comparison with the CTL or SDOM group. At 12 weeks postoperatively, the mechanical properties of reparative tissue were significantly better in the CBD-GFs/SDOM group than in the other groups. Conclusion: The CBD-GFs/SDOM is a promising scaffold for osteochondral regeneration. Clinical Relevance: The findings of this study indicated that the CBD-GFs/SDOM is an excellent candidate for reconstructing osteochondral defects, which may be translated for clinical use in the future. [ABSTRACT FROM AUTHOR]

Background: Chronic full-thickness rotator cuff tears (FTRCTs) represent a major clinical concern because they show highly compromised healing capacity. Purpose: To evaluate the efficacy of using a 3-dimensional (3D) bioprinted scaffold with human umbilical cord blood (hUCB)–mesenchymal stem cells (MSCs) for regeneration of chronic FTRCTs in a rabbit model. Study Design: Controlled laboratory study. Methods: A total of 32 rabbits were randomly assigned to 4 treatment groups (n = 8 per group) at 6 weeks after a 5-mm FTRCT was created on the supraspinatus tendon. Group 1 (G1-SAL) was transplanted with normal saline. Group 2 (G2-MSC) was transplanted with hUCB-MSCs (0.2 mL, 1 × 106) into FTRCTs. Group 3 (G3-3D) was transplanted with a 3D bioprinted construct without MSCs, and group 4 (G4-3D+MSC) was transplanted with a 3D bioprinted construct containing hUCB-MSCs (0.2 mL, 1 × 106 cells) into FTRCTs. All 32 rabbits were euthanized at 4 weeks after treatment. Examination of gross morphologic changes and histologic results was performed on all rabbits after sacrifice. Motion analysis was also performed before and after treatment. Results: In G4-3D+MSC, newly regenerated collagen type 1 fibers, walking distance, fast walking time, and mean walking speed were greater than those in G2-MSC based on histochemical and motion analyses. In addition, when compared with G3-3D, G4-3D+MSC showed more prominent regenerated tendon fibers and better parameters of motion analysis. However, there was no significant difference in gross tear size among G2-MSC, G3-3D, and G4-3D+MSC, although these groups showed significant decreases in tear size as compared with the control group (G1-SAL). Conclusion: Findings of this study show that a tissue engineering strategy based on a 3D bioprinted scaffold filled with hUCB-MSCs can improve the microenvironment for regenerative processes of FTRCT without any surgical repair. Clinical Relevance: In the case of rotator cuff tear, the cell loss of the external MSCs can be increased by exposure to synovial fluid. Therefore, a 3D bioprinted scaffold in combination with MSCs without surgical repair may be effective in increasing cell retention in FTRCT. [ABSTRACT FROM AUTHOR]

Background: Microfracture or bone marrow stimulation (BMS) is often the first choice for clinical treatment of cartilage injuries; however, fibrocartilage, not pure hyaline cartilage, has been reported because of the development of fibrosis in the repair tissue. Transforming growth factor β1 (TGF-β1), which can promote fibrosis, can be inhibited by losartan and potentially be used to reduce fibrocartilage. Hypothesis: Blocking TGF-β1 would improve cartilage healing in a rabbit knee BMS model via decreasing the amount of fibrocartilage and increasing hyaline-like cartilage formation. Study Design: Controlled laboratory study. Methods: An osteochondral defect was made in the patellar groove of 48 New Zealand White rabbits. The rabbits were divided into 3 groups: a defect group (defect only), a BMS group (osteochondral defect + BMS), and a BMS + losartan group (osteochondral defect + BMS + losartan). For the rabbits in the BMS + losartan group, losartan was administrated orally from the day after surgery through the day of euthanasia. Rabbits were sacrificed 6 or 12 weeks postoperatively. Macroscopic appearance, microcomputed tomography, histological assessment, and TGF-β1 signaling pathway were evaluated at 6 and 12 weeks postoperatively. Results: The macroscopic assessment of the repair revealed that the BMS + losartan group was superior to the other groups tested. Microcomputed tomography showed superior healing of the bony defect in the BMS + losartan group in comparison with the other groups. Histologically, fibrosis in the repair tissue of the BMS + losartan group was significantly reduced when compared with the other groups. Results obtained with the modified O'Driscoll International Cartilage Repair Society grading system yielded significantly superior scores in the BMS + losartan group as compared with both the defect group and the BMS group (F value: 15.8, P <.001, P =.012, respectively). TGF-β1 signaling and TGF-β-activated kinase 1 of the BMS + losartan group were significantly suppressed in the synovial tissues. Conclusion: By blocking TGF-β1 with losartan, the repair cartilage tissue after BMS was superior to the other groups and consisted primarily of hyaline cartilage. These results should be easily translated to the clinic because losartan is a Food and Drug Administration–approved drug and it can be combined with the BMS technique for optimal repair of chondral defects. Clinical Relevance: Biologically regulated marrow stimulation by blocking TGF-β1 (oral intake of losartan) provides superior repair via decreasing fibrocartilage formation and resulting in hyaline-like cartilage as compared with outcomes from BMS only. [ABSTRACT FROM AUTHOR]

Background: Direct impacts with the head (linear acceleration or pressure) and inertial loading of the head (rotational acceleration or strain) have been postulated as the 2 major mechanisms of head-related injuries such as concussion. Although data are accumulating for soccer and American football, there are no published data for nonhelmeted collision sports such as rugby union. Purpose: To quantify head impacts via instrumented mouthguard acceleration analyses for rugby union players over a season of matches. Study Design: Descriptive epidemiology study. Methods: Data on impact magnitude and frequency were collected with molded instrumented mouthguards worn by 38 premier amateur senior rugby players participating in the 2013 domestic season of matches. Results: A total of 20,687 impacts >10g (range, 10.0-164.9g) were recorded over the duration of the study. The mean ± SD number of impacts per player over the duration of the season of matches was 564 ± 618, resulting in a mean ± SD of 95 ± 133 impacts to the head per player, per match over the duration of the season of matches. The impact magnitudes for linear accelerations were skewed to the lower values (Sp = 3.7 ± 0.02; P<.001), with a mean linear acceleration of 22.2 ± 16.2g. Rotational accelerations were also skewed to the lower values (Sp = 2.0 ± 0.02; P < .001), with a mean rotational acceleration of 3902.9 ± 3948.8 rad/s2. Conclusion: The acceleration magnitudes and number of head impacts in amateur rugby union players over a season of matches, measured via instrumented mouthguard accelerations, were higher than for most sports previously reported. Mean linear acceleration measured over a season of matches was similar to the mean linear accelerations previously reported for youth, high school, and collegiate American football players but lower than that for female youth soccer players. Mean rotational acceleration measured over a season of matches was similar to mean rotational accelerations for youth, high school, and collegiate American football players but less than those for female youth soccer players, concussed American collegiate players, collegiate American football players, and professional American football players. [ABSTRACT FROM AUTHOR]