Heparan sulfates (HS) are key elements of the extracellular matrix (ECM), which store and protect various cell communication peptides (CCP). HS play a central role in tissue homeostasis, by modulating the bioavailability of CCP. As such, they control the cell migration and differentiation required for wound healing processes. Tissue injury will lead to destruction of cells and surrounding ECM is destroyed. CCPs synthesised by inflammatory and circulating cells can then promote tissue repair, but with a loss of tissue quality, leaving traces, scars or fibroses. We have engineered biodegradable nano-polymers mimicking the HS. They bind to the structure proteins of the damaged ECM, and to the CCP produced by healthy neighbouring cells, thereby restoring the ECM microenvironment and tissue homeostasis. This matrix therapy approach has considerably improved the quality of wound healing in various animal models. Our HS mimetics have therefore been named RGTA, for ReGeneraTing Agents. The RGTA technology has been validated in over 80 published preclinical studies and is now available as a wound healing agent both for corneal (CACICOL20) and skin ulcers (CACIPLIQ20)-see www.OTR3.com. Few thousand patients in therapeutic failure with non-healing ulcers have been successfully treated in Europe and the Middle East, suggesting great safety and efficacy with respect to both speed and quality. More controlled randomised clinical trials are ongoing. Concerning tendonitis, a dedicated injectable RGTA, namely EQUITEND, was developed and a first study measured the healing capacity on the injured tendon after unique and echo guided intra-lesion injection in 137 horses over 2 years. A controlled randomised study was performed on 32 trotters with SDFT injury and another randomised study on mechanically injured SDFT tendons in 12 laboratory horses was also documented. Altogether, these studies indicate that RGTA accelerates both speed and quality of tendon healing. RGTA treated injured racing horses had improvements on earlier echography images, returned to races 2.4 months earlier than control, their breakage recurrence was twice as low, and their gains were as high as before injury versus half in control horses. This underlines the potential of RGTA as a new therapeutic class in the field of regenerative medicine, simple safe and exploiting our natural potential without need for exogenous cells supply.
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