title: A fibrin/hyaluronic acid hydrogel for the delivery of mesenchymal stem cells and potential for articular cartilage repair.
abstract: BACKGROUND
  Osteoarthritis (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.
  
  
  RESULTS
  Increased 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.
  
  
  CONCLUSIONS
  Fibrin/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.
authors: Bioengineering Department, University of Colorado, Anschutz Medical Campus, Mail Stop 8607, 12700 East 19th Avenue, Aurora, CO 80045, USA.|Regenerative Sciences, 403 Summit Blvd, Suite 201, Broomfield, CO 80021, USA.
authors: Timothy N
authors: TN
authors: Snyder
authors: Bioengineering Department, University of Colorado, Anschutz Medical Campus, Mail Stop 8607, 12700 East 19th Avenue, Aurora, CO 80045, USA.
authors: Krishna
authors: K
authors: Madhavan
authors: Bioengineering Department, University of Colorado, Anschutz Medical Campus, Mail Stop 8607, 12700 East 19th Avenue, Aurora, CO 80045, USA.
authors: Miranda
authors: M
authors: Intrator
authors: Regenerative Sciences, 403 Summit Blvd, Suite 201, Broomfield, CO 80021, USA.
authors: Ryan C
authors: RC
authors: Dregalla
authors: Bioengineering Department, University of Colorado, Anschutz Medical Campus, Mail Stop 8607, 12700 East 19th Avenue, Aurora, CO 80045, USA.
authors: Daewon
authors: D
authors: Park
keywords: Cartilage; Fibrin; Hyaluronic acid; Hydrogel; Mesenchymal stem cell; Osteoarthritis; Regenerative medicine; Stem cell delivery; Tissue engineering