Abstract
BackgroundOsteoarthritis (OA) is a degenerative joint disease affecting approximately 27 million Americans, and even more worldwide. OA is characterized by degeneration of subchondral bone and articular cartilage. In this study, a chondrogenic fibrin/hyaluronic acid (HA)-based hydrogel seeded with bone marrow-derived mesenchymal stem cells (BMSCs) was investigated as a method of regenerating these tissues for OA therapy. This chondrogenic hydrogel system can be delivered in a minimally invasive manner through a small gauge needle, forming a three-dimensional (3D) network structure in situ. However, an ongoing problem with fibrin/HA-based biomaterials is poor mechanical strength. This was addressed by modifying HA with methacrylic anhydride (MA) (HA-MA), which reinforces the fibrin gel, thereby improving mechanical properties. In this study, a range of fibrinogen (the fibrin precursor) and HA-MA concentrations were explored to determine optimal conditions for increased mechanical strength, BMSC proliferation, and chondrogenesis potential in vitro.ResultsIncreased mechanical strength was achieved by HA-MA reinforcement within fibrin hydrogels, and was directly correlated with increasing HA-MA concentration. Live/dead staining and metabolic assays confirmed that the crosslinked fibrin/HA-MA hydrogels provided a suitable 3D environment for BMSC proliferation. Quantitative polymerase chain reaction (qPCR) of BMSCs incubated in the fibrin/HA-MA hydrogel confirmed decreased expression of collagen type 1 alpha 1 mRNA with an increase in Sox9 mRNA expression especially in the presence of a platelet lysate, suggesting early chondrogenesis.ConclusionFibrin/HA-MA hydrogel may be a suitable delivery method for BMSCs, inducing BMSC differentiation into chondrocytes and potentially aiding in articular cartilage repair for OA therapy.
Highlights
Over 30 million Americans suffer from arthritis and other rheumatic conditions, and by 2030 nearly 25% of the American population is expected to be affected by such conditions [1]
Bone marrow-derived mesenchymal stem cells (BMSC) phenotype verification Phenotypical surface protein expression of BMSCs was confirmed by flow cytometry (Figure 1) after incubating BMSCs with the antibodies unlabeled with fluorescent dyes (Figure 1A, B and C), anti-CD34 antibody (Figure 1D, E and F) and fluorescent-labeled antibodies, CD105-PE, CD73-Peridinin chlorophyll protein complex (PerCP), CD-90APC, CD44-Fluorescein isothiocyanate (FITC) & CD34-FITC (Figure 1G, H and I)
Based on the fluorescent tag of the antibodies, positive markers display a shift in their respective fluorescent channel
Summary
Over 30 million Americans suffer from arthritis and other rheumatic (affecting joints and connective tissue) conditions, and by 2030 nearly 25% of the American population is expected to be affected by such conditions [1]. Osteoarthritis (OA) represents the majority of these cases, and is characterized by loss of articular cartilage and subchondral bone. This condition causes severe pain, and is the leading cause of chronic disability in the. A chondrogenic fibrin/hyaluronic acid (HA)-based hydrogel seeded with bone marrow-derived mesenchymal stem cells (BMSCs) was investigated as a method of regenerating these tissues for OA therapy. This chondrogenic hydrogel system can be delivered in a minimally invasive manner through a small gauge needle, forming a three-dimensional (3D) network structure in situ. A range of fibrinogen (the fibrin precursor) and HA-MA concentrations were explored to determine optimal conditions for increased mechanical strength, BMSC proliferation, and chondrogenesis potential in vitro
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