Fabrication of a Novel 3D Extrusion Bioink Containing Processed Human Articular Cartilage Matrix for Cartilage Tissue Engineering.

Cartilage damage presents a significant clinical challenge due to its intrinsic avascular nature which limits self-repair. Addressing this, our study focuses on an alginate-based bioink, integrating human articular cartilage, for cartilage tissue engineering. This novel bioink was formulated by encapsulating C20A4 human articular chondrocytes in sodium alginate, polyvinyl alcohol, gum arabic, and cartilage extracellular matrix powder sourced from allograft femoral condyle shavings. Using a 3D bioprinter, constructs were biofabricated and cross-linked, followed by culture in standard medium. Evaluations were conducted on cellular viability and gene expression at various stages. Results indicated that the printed constructs maintained a porous structure conducive to cell growth. Cellular viability was 87% post printing, which decreased to 76% after seven days, and significantly recovered to 86% by day 14. There was also a notable upregulation of chondrogenic genes, COL2A1 (p = 0.008) and SOX9 (p = 0.021), suggesting an enhancement in cartilage formation. This study concludes that the innovative bioink shows promise for cartilage regeneration, demonstrating substantial viability and gene expression conducive to repair and suggesting its potential for future therapeutic applications in cartilage repair.

Psoralen: a narrative review of current and future therapeutic uses.

Psoralen is a family of naturally occurring photoactive compounds found in plants that acquire potential cytotoxicity when activated by specific frequencies of electromagnetic waves. Psoralens penetrate the phospholipid cellular membranes and insert themselves between the pyrimidines of deoxyribonucleic acid (DNA). Psoralens are initially biologically inert and acquire photoreactivity when exposed to certain classes of electromagnetic radiation, such as ultraviolet light. Once activated, psoralens form mono- and di-adducts with DNA, leading to marked cell apoptosis. This apoptotic effect is more pronounced in tumor cells due to their high rate of cell division. Moreover, photoactivated psoralen can inhibit tyrosine kinase signaling and influence the immunogenic properties of cells. Thus, the cytotoxicity of photoactivated psoralen holds promising clinical applications from its immunogenic properties to potential anti-cancer treatments. This narrative review aims to provide an overview of the current understanding and research on psoralen and to explore its potential future pharmacotherapeutic benefits in specific diseases.

The association of pre-existing mental health conditions and patient outcomes after lower extremity orthopaedic trauma: a scoping review.

INTRODUCTION: Existing research has established a correlation between post-traumatic mental health conditions, including anxiety and depression, and various aspects of recovery, such as pain exacerbations, reduced functional recovery, and lowered patient satisfaction. However, the influence of pre-existing mental health conditions on orthopaedic trauma outcomes has not been thoroughly investigated. The objective of this study was to systematically review literature addressing the association between pre-existing mental health conditions and patient outcomes following surgical interventions for lower extremity fractures in non-geriatric populations. METHODS: A systematic literature review was conducted using Medline, Embase, and Scopus databases following PRISMA-ScR guidelines to select studies that examined lower extremity orthopaedic trauma outcomes in relation to pre-existing mental health conditions. Studies that evaluated patients with surgically treated lower extremity fractures and a history of mental health conditions such as anxiety, depression, or mood disorders were included. Studies with a mean patient age above 65 years of age were excluded to focus on non-geriatric injury patterns. RESULTS: The systematic review identified 12 studies investigating the relationship between surgical outcomes of orthopaedic lower extremity fractures and pre-existing mental health disorders in non-geriatric populations. Studies included patients with pelvis, femur, tibia, and ankle fractures. A majority (83%) of these studies demonstrated that patients with pre-existing mental health diagnoses had inferior functional outcomes, heightened pain levels, or an increase in postoperative complications. DISCUSSION: The presence of pre-existing mental health conditions, particularly anxiety and depression, may predispose orthopaedic trauma patients to an elevated risk of suboptimal functional outcomes, increased pain, or complications after surgical intervention for lower extremity fractures. Future research should focus on interventions that mitigate the impact of mental health conditions on orthopaedic outcomes and patient wellness in this population.

Exposure of Tissue-Engineered Cartilage Analogs to Synovial Fluid Hematoma After Ankle Fracture Is Associated With Chondrocyte Death and Altered Cartilage Maintenance Gene Expression.

BACKGROUND: The first stage of fracture healing consists of hematoma formation with recruitment of proinflammatory cytokines and matrix metalloproteinases. Unfortunately, when there is an intra-articular fracture, these inflammatory mediators are not retained at the fracture site, but instead, envelop the healthy cartilage of the entire joint via the synovial fluid fracture hematoma (SFFH). These inflammatory cytokines and matrix metalloproteinases are known factors in the progression of osteoarthritis and rheumatoid arthritis. Despite the known inflammatory contents of the SFFH, little research has been done on the effects of the SFFH on healthy cartilage with regard to cell death and alteration in gene expression that could lead to posttraumatic osteoarthritis (PTOA). METHODS: SFFH was collected from 12 patients with intraarticular ankle fracture at the time of surgery. Separately, C20A4 immortalized human chondrocytes were 3-dimensionally cultured to create scaffold-free cartilage tissue analogs (CTAs) to simulate healthy cartilage. Experimental CTAs (n = 12) were exposed to 100% SFFH for 3 days, washed, and transferred to complete media for 3 days. Control CTAs (n = 12) were simultaneously cultured in complete medium without exposure to SFFH. Subsequently, CTAs were harvested and underwent biochemical, histological, and gene expression analysis. RESULTS: Exposure of CTAs to ankle SFFH for 3 days significantly decreased chondrocyte viability by 34% (P = .027). Gene expression of both COL2A1 and SOX9 were significantly decreased after exposure to SFFH (P = .012 and P = .0013 respectively), while there was no difference in COL1A1, RUNX2, and MMP13 gene expression. Quantitative analysis of Picrosirius red staining demonstrated increased collagen I deposition with poor ultrastructural organization in SFFH-exposed CTAs. CONCLUSION: Exposure of an organoid model of healthy cartilage tissue to SFFH after intraarticular ankle fracture resulted in decreased chondrocyte viability, decreased expression of genes regulating normal chondrocyte phenotype, and altered matrix ultrastructure indicating differentiation toward an osteoarthritis phenotype. CLINICAL RELEVANCE: The majority of ankle fracture open reduction and internal fixation does not occur immediately after fracture. In fact, typically these fractures are treated several days to weeks later in order to let the swelling subside. This means that the healthy innocent bystander cartilage not involved in the fracture is exposed to SFFH during this time. In this study, the SFFH caused decreased chondrocyte viability and specific altered gene expression that might have the potential to induce osteoarthritis. These data suggest that early intervention after intraarticular ankle fracture could possibly mitigate progression toward PTOA.