Stimulated neovascularization, inflammation resolution and collagen maturation in healing rat cutaneous wounds by a heparan sulfate glycosaminoglycan mimetic, OTR4120

  title={Stimulated neovascularization, inflammation resolution and collagen maturation in healing rat cutaneous wounds by a heparan sulfate glycosaminoglycan mimetic, OTR4120},
  author={Miao Tong and Bastiaan Tuk and Ineke M. Hekking and Marcel Vermeij and Denis Barritault and Johan W. van Neck},
  journal={Wound Repair and Regeneration},
Heparan sulfate glycosaminoglycans (HS‐GAGs) are not only the structural elements of tissue architecture but also regulate the bioavailability and transduction pathways of heparan sulfate‐bound polypeptides released by cells or the extracellular matrix. Heparan sulfate‐bound polypeptides include inflammatory mediators, chemokines, angiogenic factors, morphogens, and growth‐promoting factors that induce cell migration, proliferation, and differentiation in wound healing. OTR4120, a polymer… 
Diabetes-Impaired Wound Healing Is Improved by Matrix Therapy With Heparan Sulfate Glycosaminoglycan Mimetic OTR4120 in Rats
This study shows that matrix therapy with OTR4120 improves diabetes-impaired wound healing, and restoration of the ulcer biomechanical strength was significantly enhanced after O TR4120 treatment.
Glycosaminoglycan content of a mineralized collagen scaffold promotes mesenchymal stem cell secretion of factors to modulate angiogenesis and monocyte differentiation
It is demonstrated that modifying mineralized collagen scaffold GAG content can both directly (hMSC activity) and indirectly (endogenous production of secreted factors) influence overall osteogenic potential and mineral biosynthesis as well as angiogenic Potential and monocyte differentiation towards osteoclastic and macrophage lineages.
The Pharmaceutical Device Prisma® Skin Promotes in Vitro Angiogenesis through Endothelial to Mesenchymal Transition during Skin Wound Healing
It is suggested that Prisma® Skin may be able to accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding chronic, thus pathological, responses.
Ski, a modulator of wound healing and scar formation in the rat skin and rabbit ear
It is shown that increasing local Ski expression by gene transfer not only significantly accelerated wound healing by relieving inflammation, accelerating re‐epithelialization and increasing formation of granulation tissue, but also reduced scar formation by decreasing collagen production in rat dermal wounds.
Natural and synthetic polymers for wounds and burns dressing.
TAT-Mediated Acidic Fibroblast Growth Factor Delivery to the Dermis Improves Wound Healing of Deep Skin Tissue in Rat
It is demonstrated that TAT-aFGF has a favorable therapeutic effect on the healing of subcutaneous deep tissue injury and reversed the suppressive effect of TNF-α on α-SMA expression and restored TGF-βRII and T GF-β1 expression.
Heparan sulfate glycosaminoglycan mimetic improves pressure ulcer healing in a rat model of cutaneous ischemia‐reperfusion injury
  • Miao Tong, B. Tuk, J. V. van Neck
  • Medicine, Biology
    Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
  • 2011
It is concluded that OTR4120 treatment reduces pressure ulcer formation and potentiates the internal healing bioavailability and long‐term restoration of wounded tissue biomechanical strength was significantly enhanced after OTR 4120 treatment.
Comparative evaluation of the wound-healing potency of recombinant bFGF and ski gene therapy in rats
Results not only confirm that Ski plays a dual role in promoting healing and reducing scarring but also suggest that Ski yields better treatment effects than bFGF, indicating better potential therapeutic effects in wound repair.


Matrix therapy in regenerative medicine, a new approach to chronic wound healing.
It is shown that a specific biopolymer accelerates ulcer closure and improves re-epithelialization and dermal-matrix-component remodeling and appropriate polymer-based matrix therapy is a valid and simple alternative to regenerative medicine.
Heparin-like synthetic polymers, named RGTAs, mimic biological effects of heparin in vitro.
A family of biopolymers engineered to protect and stabilize heparin binding growth factors (HBGFs) show remarkable properties as wound healing agents in several in vivo tissue repair models to the
Mechanisms of wound reepithelialization: hints from a tissue‐engineered reconstructed skin to long‐standing questions
A tissue‐engineered wound‐healing model composed of human skin keratinocytes and fibroblasts is developed to better understand the mechanisms of reepithelialization, which was significantly accelerated in the presence of fibrin or platelet‐rich plasma.
RGTA OTR4120, a heparan sulfate mimetic, is a possible long-term active agent to heal burned skin.
ReGeneraTing Agent (RGTA) reduces burn-induced skin alteration and enhanced healing in short- and long-term after burns, reducing the formation of fibrotic tissue, and then represents a potential agent to improve burned skin healing.
Significant reduction in neural adhesions after administration of the regenerating agent OTR4120, a synthetic glycosaminoglycan mimetic, after peripheral nerve injury in rats.
The RGTAs strongly reduce nerve adherence to surrounding tissue after nerve crush injury, and results of the static footprint analysis demonstrate no improved or accelerated recovery pattern.
[Regenerating agents (RGTAs): a new therapeutic approach].
Observations indicate that mammals have an unexpected ability to regenerate and that RGTA helps to reveal this capacity as well as developing RGTA into a drug to treat specific tissue lesions.
Patterns of matrix metalloproteinase and TIMP expression in chronic ulcers
Investigating how chronic leg ulcers differ from normally healing wounds with respect to their metalloproteinase expression patterns found that collagenase-1, stromelysin-1 (MMP-3) and stromelyin-2 (M MP-10) were expressed in keratinocytes bordering both acute and chronic wounds, suggesting controlled proteolysis is needed for cell migration, angiogenesis, and matrix remodeling during normal wound repair.
Dynamics of the matrix metalloproteinases MMP‐1 and MMP‐8 in acute open human dermal wounds
New evidence is provided implicating matrix metalloproteinase‐8 as a major collagenase in healing human dermal wounds and suggesting that a tightly regulated pattern of expression of matrix metaloproteinases and their inhibitors is essential for normal wound healing in humans.
Expression and proteolysis of vascular endothelial growth factor is increased in chronic wounds.
Data show that, although vascular endothelial growth factor expression is elevated in chronic wounds, increased proteolytic activity in this environment results in its degradation, which may contribute to an impaired wound healing response.