Diabetes-Impaired Wound Healing Is Improved by Matrix Therapy With Heparan Sulfate Glycosaminoglycan Mimetic OTR4120 in Rats

Abstract

Wound healing in diabetes is frequently impaired, and its treatment remains a challenge. We tested a therapeutic strategy of potentiating intrinsic tissue regeneration by restoring the wound cellular environment using a heparan sulfate glycosaminoglycan mimetic, OTR4120. The effect of OTR4120 on healing of diabetic ulcers was investigated. Experimental diabetes was induced by intraperitoneal injection of streptozotocin. Seven weeks after induction of diabetes, rats were ulcerated by clamping a pair of magnet disks on the dorsal skin for 16 h. After magnet removal, OTR4120 was administered via an intramuscular injection weekly for up to 4 weeks. To examine the effect of OTR4120 treatment on wound heal-ing, the degree of ulceration, inflammation, angiogenesis, and collagen synthesis were evaluated. We found that OTR4120 treatment significantly reduced the degree of ulceration and the time of healing. These effects were associated with reduced neutrophil infiltration and macrophage accumulation and enhanced angiogenesis. OTR4120 treatment also increased the collagen content with an increase of collagen type I biosynthesis and reduction of collagen type III biosynthesis. Moreover, restoration of the ulcer biomechanical strength was significantly enhanced after OTR4120 treatment. This study shows that matrix therapy with OTR4120 improves diabetes-impaired wound healing.

Hyperbaric oxygen therapy for wound healing in diabetic rats: Varying efficacy after a clinically-based protocol

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ReGeneraTing Agents (RGTA®): A new option for healing and improving treatment outcomes for traumatic and burn injuries of the hand

“…They protect naturally existing structural and signaling proteins by sequestering proteins through low‐affinity binding, allowing for faster and high‐quality tissue repair . Their unique properties have been the subject of intensive preclinical and clinical studies . CACIPLIQ20 ® contains RGTA ® OTR4120, a biodegradable polymer of 1‐6 alpha polyglucose substituted carboxymethyl and sulfated …”

ReGeneraTing Agents (RGTA®) are a new option to improve amputation outcomes in the recovery of severe hand injuries

“…RGTA ® s are heparan sulfate (HS) mimetics specifically designed to replace degraded heparan sulfates in damaged tissue, accelerating the speed and enhancing the quality of tissue repair 4. Their unique properties have been the subject of intensive preclinical and clinical studies 2, 3, 6, 7, 8, 9, 10, 11, 12. CACIPLIQ20 ® contains RGTA ® OTR4120, a biodegradable polymer of 1‐6 alpha polyglucose substituted with carboxymethyl and sulfated groups 4.…”