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Research

AN EX VIVO HUMAN FEMORAL HEAD MODEL FOR ORTHOBIOLOGIC THERAPIES

The British Orthopaedic Research Society (BORS) Annual Meeting 2020, held online, 7–8 September 2020.



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.