Speaker
Description
SELF-ASSEMBLING PEPTIDE GELS FOR ARTICULAR PATELLA CARTILAGE REPAIR
James Warrena,b,c, Raelene Cowiea, Louise Jenningsa, Ruth Wilcoxa, Hazel Fermora,b
a Institute of Biological and Medical Engineering,b Faculty of Biological Sciences, c Bragg Centre for Materials Research, University of Leeds, Leeds, LS2 9JT
J.P.Warren@leeds.ac.uk
INTRODUCTION
Loss of cartilage glycosaminoglycans (GAGs) leads to reduced biomechanical function [1]. This change is seen in the early stages of osteoarthritis (OA) and in other joint disorders such as Chondromalacia patella (CP), where softening of patella cartilage is associated pain. There is a clinical need for early intervention treatments to restore cartilage function and delay the progression of cartilage degeneration. Delivery of self-assembling peptide (SAP) hydrogels combined with chondroitin sulfate (CS) into damaged cartilage may restore the GAG content and biomechanical function, specifically patella and femoral cartilage [2] [3].
The aim of this study was to develop an in vitro GAG-depleted patella model and assess the biomechanical effects following treatment with a SAP:CS self-assembling hydrogel.
Methodology
Model: 4-6 month old porcine patellae were harvested and washed with 0.1% (w/v) SDS to remove GAGs from the cartilage. Histological and biochemical analysis was carried out to assess GAG removal and any changes to the tissue architecture (n=6).
SAP:CS treatment: Indentation testing (n=6 per group) was performed on native, GAG depleted patellae, and a SAP:CS treated group. SAP:CS (~ 6mM SAP and 10 mg CS in Ringers) was injected into a 10 mm2 area of cartilage through a 30 G needle.
RESULTS
The GAG depletion process removed 56±12% of the sulphated GAGs within porcine patella cartilage (mean ± 95% C.I.). Histological analysis of the GAG depleted samples showed GAG loss with the remaining architecture unaffected.
A significant increase in percentage deformation was seen in the GAG depleted group compared to native cartilage (n=6, p<0.001). Treated samples showed significant reduction in percentage deformation compared to the depleted group (n=6, p<0.05) and no significant difference to native cartilage (Figure 1).
CONCLUSIONS
The ~50% reduction of GAGs represented a moderate osteoarthritic cartilage model and did not cause observable changes in the tissue architecture or collagen orientation. GAG loss resulted in a significant reduction in cartilage stiffness which was successfully restored by treatment with SAP:CS. Future work is underway to investigate the biotribological effects of SAP:CS through the use of a six-axis natural joint simulator. SAP:CS has potential to be an effective treatment for CP and early OA.
ACKNOWLEDGEMENTS
Project funded by EPSRC (grant number: EP/P001076/1).
REFERENCES
[1] Macri, Erin M. et al, J. Clin. Med., 9(11):3397, 2020.
[2] Barco, Andres et al, J. Pept. Sci., 24(8-9), 2018.
[3] Warren, James P. et al, Adv. Healthcare Mater., 10, 2021."
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