Objective Biologics are increasingly used for cartilage repair and osteoarthritis (OA) treatment. This study aimed to provide an overview of the clinical trials conducted on this subject. Design Two-word combinations of two sets of key words “cartilage”; “joint”; “osteoarthritis” and “biologics”; “stem cells”; “cell implantation” were used to search the database of ClinicalTrials.gov and supplemented with searches of PubMed and EMbase. The registered trials were analyzed for clinical conditions, completion status, phases, and investigated biologics. Recently completed trials with posted/published results were summarized. Results From 2000 to 2022, a total of 365 clinical trials were registered at ClinicalTrials.gov to use biologics for cartilage repair and OA treatment. Since 2006, the number of registered trials accelerated at an annual rate of 16.4%. Of the 265 trials designated with a phase, 72% were early Phase 1, Phase 1, and Phase 2. Chondrocytes and platelet-rich plasma (PRP) were studied in nearly equal number of early- and late-stage trials. Mesenchymal stem/stromal cells (MSCs) were the most commonly investigated biologics (38%) and mostly derived from bone marrow and adipose tissue (70%). In last 5 years, 32 of the 72 completed trials posted/published results, among which seven Phase 3 trials investigated chondrocytes, PRP, bone marrow aspirate concentrate, hyaluronic acid, collagen membrane, and albumin. Conclusions There was a rapid increase in the number of registered clinical trials in recent years, using a variety of biologics for cartilage repair and OA treatment. Majority of the biologics still require late-stage trials to validate their clinical effectiveness.
Background: Assessing patient’s risk of infection is fundamental for prevention of periprosthetic joint infection (PJI) after total ankle arthroplasty (TAA). The Mayo Prosthetic Joint Infection Risk Score (Mayo Score) is based on data from total hip and knee arthroplasty and has not been validated for application for TAA. Methods: A total of 405 consecutive TAA cases were followed for 6 months for PJI. Individual patients’ Mayo Scores were calculated and analyzed with logistic regression and receiver operating characteristic (ROC) for predictability for PJI. A critical cut-off Mayo Score for patients at high risk of PJI was determined by best Youden index. Among the Mayo Score–defined high-risk patients, the contribution of different risk factors were compared between the PJI and non-PJI patients. Results: There were 10 cases of PJI (2.5%) among the 405 cases within 6 months after TAA. Of the 405 patients, the Mayo Scores ranged between −4 and 13 (median 2; interquartile range 0-5). The average Mayo Score was 2.5 ± 3.4 in the non-PJI patients and 7.7 ± 3.1 in the PJI patients ( P < .001). Logistic regression showed that the probability of PJI increased with higher Mayo Scores (odds ratio 1.48, 95% CI 1.23-1.78). All but 1 PJI patients had a Mayo Score >5. The sensitivity and specificity were 90.0% and 84.3%, respectively, when a Mayo Score >5 was used as a criterion for high risk of PJI. Conclusion: This study demonstrated that the Mayo Score could similarly predict PJI risk after TAA as in total hip and knee arthroplasty. Data analysis suggests that a Mayo Score >5 could be a criterion for identifying high-risk patients for PJI, although further validation with a large number of PJI cases is necessary. Level of Evidence: II, developing diagnositic criteria with consecutive cases.
This study described and histologically characterized a cyst-like lesion (CLL) at the chondro-osseous junction. Rat knees (n = 12), with or without excessive running-induced osteoarthritis (OA), were used for counting the incidence, morphological measurements, immunohistochemistry of the CLL. A typical CLL, appearing as a void space in the matrix, was located on the tidemark at the chondro-osseous junction. The content of the CLL included types II and VI collagen, proteoglycans but not intact chondrocytes. At least one CLL was found in 5/6 osteoarthritic knees and only 2/6 in the non-osteoarthritic knees. The margin of the CLL was depleted of proteoglycans. The chondrocytes around the lesion were deformed and occasionally apoptotic. Matrix metalloproteinase 13 and vascular endothelial growth factor receptor were not detected in and around the CLL. CLLs disrupt the integrity of cartilage at a mechanically critical location-the chondro-osseous junction. The significance of the CLL in cartilage biology and its potential role in OA pathogenesis warrant further investigation.
Foot fat pad (FFP) is a highly functionalized fat depot of great significance for weight bearing in the foot. Mesenchymal stromal cells (MSCs) in subcutaneous adipose tissues are widely studied for regenerative potentials. MSCs in FFP, which may contribute to the physiological and pathological conditions of the foot, have not been characterized. In this study, MSCs were isolated from FFP (designated as MSCs-ffp) and subcutaneous adipose tissue (designated as MSCs-sub) from rats. The cell surface markers, proliferation, and efficiency of colony formation were compared between MSCs-ffp and MSCs-sub. In addition, MSCs-ffp were induced for osteogenic, chondrogenic, and adipogenic differentiation. The tri-lineage differentiation potentials were compared between MSCs-ffp and MSCs-sub by the expression of Runx2, Sox9, and proliferatoractivated receptor gamma (PPAR-γ), respectively, using quantitative polymerized chain reaction. The expression of elastin and associated genes by MSCsffp were also evaluated. MSCs-ffp, like MSCs-sub, expressed CD44, CD73, and CD90. MSCs-ffp and MSCs-sub proliferated at similar rates but MSCs-ffp formed more colonies than MSCs-sub. MSCs-ffp were capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages. Under the conditions of osteogenic and adipogenic differentiation, MSCs-sub expressed more Runx2 and PPAR-γ, respectively, than MSCs-ffp. The undifferentiated MSCs-ffp upregulated the expression of fibulin-5. In conclusion, MSCs-ffp shared common biology with MSCs-sub but were more efficient in colony formation, less adipogenic and osteogenic, and participated in elastogenesis. The unique features of MSCs-ffp may relate to their roles in the physiological functions of FFP. K E Y W O R D S adipose tissue, foot fat pad, mesenchymal stromal cell 1 | INTRODUCTION Adipose tissue is among the most abundant in the body and principally serves to store and release energy (Tchkonia et al., 2013). According to the functions of adipocytes, adipose tissues are classified into two categories: (a) white adipose tissue, which stores and mobilizes energy in the form of triglycerides; (b) brown adipose tissue, which mainly functions in thermogenesis (Giralt &
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