title: RGTA®or ReGeneraTing Agents mimic heparan sulfate in regenerative medicine: from concept to curing patients.
abstract: The importance of extracellular matrix (ECM) integrity in maintaining normal tissue function is highlighted by numerous pathologies and situations of acute and chronic injury associated with dysregulation or destruction of ECM components. Heparan sulfate (HS) is a key component of the ECM, where it fulfils important functions associated with tissue homeostasis. Its degradation following tissue injury disrupts this delicate equilibrium and may impair the wound healing process. ReGeneraTing Agents (RGTA®s) are polysaccharides specifically designed to replace degraded HS in injured tissues. The unique properties of RGTA®(resistance to degradation, binding and protection of ECM structural and signaling proteins, like HS) permit the reconstruction of the ECM, restoring both structural and biochemical functions to this essential substrate, and facilitating the processes of tissue repair and regeneration. Here, we review 25 years of research surrounding this HS mimic, supporting the mode of action, pre-clinical studies and therapeutic efficacy of RGTA®in the clinic, and discuss the potential of RGTA®in new branches of regenerative medicine.
authors.affiliation: OTR3, 4 rue Française, 75001, Paris, France. denis.barritault@otr3.com.|Laboratory Cell Growth and Tissue Repair (CRRET), UPEC 4397/ERL CNRS 9215, Université Paris Est Cretéil, Université Paris Est, F-94000, Créteil, France. denis.barritault@otr3.com.
authors.forename: Denis
authors.identifier: 0000-0003-0315-7444
authors.initials: D
authors.lastname: Barritault
authors.affiliation: OTR3, 4 rue Française, 75001, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Gilbert-Sirieix
authors.affiliation: OTR3, 4 rue Française, 75001, Paris, France.
authors.forename: Kim Lee
authors.initials: KL
authors.lastname: Rice
authors.affiliation: OTR3, 4 rue Française, 75001, Paris, France.
authors.forename: Fernando
authors.initials: F
authors.lastname: Siñeriz
authors.affiliation: Laboratory Cell Growth and Tissue Repair (CRRET), UPEC 4397/ERL CNRS 9215, Université Paris Est Cretéil, Université Paris Est, F-94000, Créteil, France.
authors.forename: Dulce
authors.initials: D
authors.lastname: Papy-Garcia
authors.affiliation: Institut de la Vision, 17 rue Moreau, 75012, Paris, France.|Universite Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 55 Avenue de Paris, 78000, Versailles, France.|Centre Hospitalier National d'Opthalmologie des Quinze Vingts, 28 rue de Charenton, 75012, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Baudouin
authors.affiliation: Department of Vascular Surgery, Hopital Henri Mondor, Université Paris-Est Créteil, 51 avenue du Maréchal de Lattre de Tassigny, 94000, Créteil, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Desgranges
authors.affiliation: Service de Chirurgie Plastique et Reconstructrice, 33 rue de la Tour, Paris, 75016, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Zakine
authors.affiliation: EA2496 Laboratoire Pathologies, Imagerie et Biothérapies Oro-Faciales, Faculté de Chirurgie Dentaire, Université Paris Descartes, Sorbonne Paris Cité, 1 rue Maurice Arnoux, 92120, Montrouge, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Saffar
authors.affiliation: Department of Plastic and Reconstructive Surgery, Erasmus MC - University Medical Center, Rotterdam, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: van Neck
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects / Q000293:injuries; D002986:Clinical Trials as Topic; D065306:Corneal Injuries / Q000188:drug therapy* / Q000534:rehabilitation; D004353:Drug Evaluation, Preclinical; D005109:Extracellular Matrix / Q000737:chemistry; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000293:injuries; D006025:Glycosaminoglycans / Q000737:chemistry / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009132:Muscles / Q000187:drug effects / Q000293:injuries; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D044968:Regenerative Medicine / Q000379:methods; D012867:Skin / Q000187:drug effects* / Q000293:injuries; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D020011:Protective Agents; C533322:OTR4120
keywords: Extracellular scaffold; Heparan sulfate mimics; RGTA®; Regeneration