Abstract
Abstract
Objectives
The development of promising therapeutics for cartilage repair/regeneration have been hampered by the inadequacy of existing animal models and lack of suitable translational ex-vivo human tissue models. There is an urgent unmet need for these to assess repair/regenerative (orthobiologic) treatments directly in human tissue. We describe methodology allowing the successful long-term ex-vivo culture of non-degenerate whole human femoral heads that may be used as a model for testing new orthobiologic therapies.
Methods
Fifteen fresh, viable human femoral heads were obtained from 15 patients (with ethical permission/consent) undergoing hemiarthroplasty for hip fracture, and cultured aseptically (37°C) for up to 10wks. Culture conditions included static/stirred standard media (Dulbecco's modified Eagle's medium; DMEM) and supplementation with 10% human serum (HS). Chondrocyte viability, density, cell morphology, cell volume, glycosaminoglycan(GAG)/collagen content, surface roughness and cartilage thickness were quantified over time.
Results
Chondrocyte viability remained highest (>95%;P<0.01;N(n)=3(12)) under static culture conditons in DMEM+10%HS and was maintained over 10wks. In static DMEM culture without 10%HS, viability remained high for ∼4wks, then decreased rapidly (N(n)=4(16)). Chondrocyte viability declined to <35% over 10wks under all other conditions (N(n)=4(16)). Culturing femoral heads in optimal media (DMEM+10%HS) for 10wks increased the number of chondrocytes producing cytoplasmic processes (P<0.002), but decreased cartilage thickness (P<0.002) and GAG content (P=0.028). Cartilage surface roughness, cellular density, chondrocyte volume and collagen content remained unchanged (P>0.05).
Conclusions
The viability of human femoral head articular cartilage could be maintained over 10wks in ex-vivo culture. The model may allow testing of a wide range of orthobiologic therapies directly in human tissue, paving the way for subsequent targeted clinical studies of laboratory-proven strategies with the potential to repair/regenerate articular cartilage.
Funder
Chief Scientist's Office, Scotland (Grant TCS/18/01).
Declaration of Interest
(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
