Background:The incidence of coexisting osteochondral lesions (OCLs) of the tibia and talus has been negatively correlated with successful clinical outcomes, yet these lesions have not been extensively characterized.Purpose:To determine the incidence of coexisting tibial and talar OCLs, assess the morphologic characteristics of these lesions, and evaluate whether these characteristics are predictive of outcome.Study Design:Case series; Level of evidence, 4.Methods:A total of 83 patients who underwent surgery for a talar OCL were evaluated for coexisting OCLs of the distal tibia with preoperative magnetic resonance images. Size, location, containment, International Cartilage Repair Society (ICRS) grade, patient age, and patient sex were analyzed for predictors of coexisting lesions or patient outcome. The talar and tibial surfaces were each divided into 9 zones, with 1 corresponding to the most anteromedial region and proceeding laterally and then posteriorly. The Foot and Ankle Outcome Score (FAOS) was evaluated pre- and postoperatively.Results:Twenty-six patients (31%) had coexisting tibial and talar OCLs, with 9 (35%) identified as kissing lesions. Age correlated with coexisting lesion incidence, as older patients were more likely to have a coexisting tibial OCL (P = .038). More than half of talar OCLs were found in zone 4 (61%), whereas the majority of tibial OCLs were located in zones 2, 4, and 5 (19% each). Patients with coexisting lesions were more likely to have a lateral talar OCL (P = .028), while those without a coexisting tibial lesion were more likely to have a talar OCL in zone 4 (P = .016). There was no difference in FAOS result or lesion size between patients with and without coexisting OCLs, but patients with coexisting lesions were more likely to have an ICRS grade 4 talar OCL (P = .034). For patients with coexisting lesions, kissing lesions were more likely to be located in zone 6 (P = .043). There was no difference in OCL size or containment between kissing and nonkissing coexisting OCLs.Conclusion:The incidence of coexisting talar and tibial OCLs may be more prevalent than what previous reports have suggested, with older patients being more likely to present with this pathology. The location of a talar OCL correlates with the incidence of a coexisting tibial OCL.

Fibrin sealants are commonly used in cartilage repair surgeries to adhere cells or grafts into a cartilage defect. Both autologous and commercial allogeneic fibrin sealants are used in cartilage repair surgeries, yet there are no studies characterizing and comparing the mechanical properties of fibrin sealants from all-autologous sources. The objectives of this study were to investigate (i) the effect of fibrinogen and thrombin sources on failure mechanics of sealants, and (ii) how sealants affect the adhesion of particulated cartilage graft material (BioCartilage) to surrounding cartilage under physiological loading. Allogeneic thrombin and fibrinogen were purchased (Tisseel), and autologous sources were prepared from platelet-rich plasma (PRP) and platelet-poor plasma (PPP) generated from human blood. To compare failure characteristics, sealants were sandwiched between cartilage explants and pulled to failure. The effect of sealant on the adhesion of BioCartilage graft to cartilage was determined by quantifying microscale strains at the graft-cartilage interface using an in vitro cartilage defect model subjected to shear loading at physiological strains well below failure thresholds. Fibrinogen sources were not equivalent; PRP fibrinogen created sealants that were more brittle, failed at lower strains, and resulted in sustained higher strains through the graft-cartilage interface depth compared to PPP and allogeneic sources. PPP clotted slower compared to PRP, suggesting PPP may percolate deeper into the repair to provide more stability through the tissue depth. There was no difference in bulk failure properties or microscale strains at the graft-cartilage interface between the purely autologous sealant (autologous thrombin + PPP fibrinogen) and the commercial allogeneic sealant. Clinical Significance: All-autologous fibrin sealants fabricated with PPP have comparable adhesion strength as commercial allogeneic sealants in vitro, whereas PRP creates an inferior all-autologous sealant that sustains higher strains through the graft-cartilage interface depth.

Cartilage and other skeletal soft tissues heal poorly after injury, in part due to their lack of vascularity and low metabolic rate. No pharmacologic approaches have proven effective in preventing chronic degenerative disease after joint injury. Mesenchymal stromal cells (MSCs) have been investigated for their ability to treat pain associated with osteoarthritis (OA) and preserve articular cartilage. Limitations of MSCs include variability in cell phenotype, low engraftment and retention rates, and inconsistent clinical outcomes. Therefore, acellular biologic therapies such as extracellular vesicles (EVs) are currently being investigated. MSC-derived EVs have been found to replicate many of the therapeutic effects of their cells of origin, but the mechanisms driving this remain unclear. Recent evidence in non-orthopedic tissues suggests MSCs can rescue injured cells by donating mitochondria, restoring mitochondrial function in recipient cells, preserving cell viability, and promoting tissue repair. Our group hypothesized that MSCs package mitochondria for export into EVs, and that these so-called “mitoEVs” could provide a delivery strategy for cell-free mitochondria-targeted therapy. Therefore, the goals of this study were to: 1) characterize the vesicle fractions of the MSCs secretome with respect to mitochondrial cargoes, 2) determine if MSC-EVs contain functional mitochondria, and 3) determine if chondrocytes can take up MSC-derived mitoEVs. We isolated exosome, microvesicle, and vesicle-free fractions from MSC-conditioned media. Using a combination of dynamic light scattering and nanoparticle tracking, we determined that MSC-EV populations fall within the three size categories typically used to classify EVs (exosomes, microvesicles, apoptotic bodies). Fluorescent nanoparticle tracking, immunoblotting, and flow cytometry revealed that mitochondrial cargoes are abundant across all EV size populations, and mitoEVs are nearly ubiquitous among the largest EVs. Polarization staining indicated a subset of mitoEVs contain functional mitochondria. Finally, flow cytometry and fluorescent imaging confirmed uptake of mitoEVs by chondrocytes undergoing rotenone/antimycin-induced mitochondrial dysfunction. These data indicate that MSCs package intact, functional mitochondria into EVs, which can be transferred to chondrocytes in the absence of direct cell-cell interactions. This work suggests intercellular transfer of healthy MT to chondrocytes could represent a new, acellular approach to augment mitochondrial content and function in poorly-healing avascular skeletal soft tissues.

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