Abstract
The crosslinking agent genipin is increasingly invoked for the mechanical augmentation of collagen tissues and implants, and has previously been demonstrated to arrest mechanical damage accumulation in various tissues. This study established an in vitro dose–response baseline for the effects of genipin treatment on tendon cells and their matrix, with a view to in vivo application to the repair of partial tendon tears. Regression models based on a broad range of experimental data were used to delineate the range of concentrations that are likely to achieve functionally effective crosslinking, and predict the corresponding degree of cell loss and diminished metabolic activity that can be expected. On these data, it was concluded that rapid mechanical augmentation of tissue properties can only be achieved by accepting some degree of cytotoxicity, yet that post-treatment cell survival may be adequate to eventually repopulate and stabilize the tissue. On this basis, development of delivery strategies and subsequent in vivo study seems warranted.
Highlights
Crosslinking has long been employed to augment the mechanical properties of collagen-based implants for the repair or replacement of musculoskeletal and cardiovascular tissues [1,2,3]
Tissue and biomaterial crosslinking strategies, traditionally using glutaraldehyde, have almost exclusively focused on ex vivo chemical treatments of an implant prior to its application, in vivo exogenous crosslinking has more recently been pursued
While cell rounding was noted at intermediate concentrations, the two highest tested GEN concentrations (10 and 20 mM) apparently fixed the cell morphology in an elongated state, which is normal for tenocytes
Summary
Crosslinking has long been employed to augment the mechanical properties of collagen-based implants for the repair or replacement of musculoskeletal and cardiovascular tissues [1,2,3]. The physiological environments of these systems can expose implants to extreme physical demands that include high mechanical stresses, high mechanical strains and/or highly repetitive loading Such loading regimes can overwhelm even native tissues, a fact that is evidenced by high clinical rates of connective tissue disease and injury [4]. Tissue and biomaterial crosslinking strategies, traditionally using glutaraldehyde, have almost exclusively focused on ex vivo chemical treatments of an implant prior to its application, in vivo exogenous crosslinking has more recently been pursued (as we recently reviewed in detail [5]). In this paradigm, the collagen matrix of injured tissue is bolstered by judicious and targeted.
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