Meddahi A, Caruelle J P, Gold L, Rosso Y, Barritault D
Laboratoire d'étude sur la Croissance, la Réparation et la Régénération Tissulaire URA CNRS 1813, Université Paris Val de Marne, Créteil, France.
Diabetes Metab. 1996 Jul;22(4):274-8.
Several heparin-binding growth factors (HBGFs) are thought to play a key role in natural processes of tissue regeneration or repair after release from inflammatory or circulating cells and extracellular matrix-associated heparan sulfate proteoglycosaminoglycans. To clarify how the bioavailability of these HBGFs can help regulate wound-healing processes, we studied the healing effect of various chemically substituted dextrans (RGTA) selected for their affinity for HBGFs. One member of the RGTA family, RGTA11, obtained by substitution of carboxymethyl (CM), benzylamide (B) and benzylamide sulfonate (S) groups in a proportion of 110% (CM), 2.6% (B) and 36.5% (S) respectively was used in these studies. RGTA11 may potentiate the biological activity of fibroblast growth factors 1 and 2 and protect them against heat or pH inactivation and proteolytic degradation. RGTA11 was tested in a rat punch-biopsy skin-healing model for its ability to enhance wound repair. Wounds were filled with collagen plaster alone or soaked with RGTA, and skin regeneration was studied by histological analysis. In collagen plaster, RGTA11 affected both the kinetics and quality of restored skin. It seems likely that endogenous growth factors naturally released during the regeneration process are trapped and protected against natural proteases, thereby preserving their ability to stimulate tissue repair. Since most known growth factors have a nearly ubiquitous distribution and blind to heparin, our hypothesis was verified by studying the ability of RGTA to induce repair in damaged tissue. We demonstrated the RGTA could stimulate wound repair in various models, including bone, muscle, nerve, cornea and colonic anastomosis. The data presented here concern wound-healing in a deep skin model and suggest that heparan-like biopolymers constitute a new family of tissue-repair agents with a wide variety of potential uses. The efficiency of this approach in cases in which impaired healing is associated with a pathology, as in diabetes, remains to be determined.
几种肝素结合生长因子（HBGFs）被认为在从炎症细胞或循环细胞以及细胞外基质相关的硫酸乙酰肝素蛋白聚糖释放后，在组织再生或修复的自然过程中起关键作用。为了阐明这些HBGFs的生物利用度如何有助于调节伤口愈合过程，我们研究了因其对HBGFs的亲和力而选择的各种化学取代葡聚糖（RGTA）的愈合效果。RGTA家族的一个成员RGTA11，通过分别以110%（羧甲基，CM）、2.6%（苄基酰胺，B）和36.5%（苄基酰胺磺酸盐，S）的比例取代羧甲基、苄基酰胺和苄基酰胺磺酸盐基团获得，用于这些研究。RGTA11可能增强成纤维细胞生长因子1和2的生物活性，并保护它们免受热、pH失活和蛋白水解降解。在大鼠打孔活检皮肤愈合模型中测试了RGTA11增强伤口修复的能力。伤口单独用胶原蛋白膏填充或用RGTA浸泡，通过组织学分析研究皮肤再生情况。在胶原蛋白膏中，RGTA11影响了修复皮肤的动力学和质量。在再生过程中自然释放的内源性生长因子似乎被捕获并免受天然蛋白酶的作用，从而保留了它们刺激组织修复的能力。由于大多数已知的生长因子分布几乎无处不在且对肝素不敏感，我们通过研究RGTA在受损组织中诱导修复的能力来验证我们的假设。我们证明了RGTA可以在包括骨、肌肉、神经、角膜和结肠吻合术在内的各种模型中刺激伤口修复。这里呈现的数据涉及深皮肤模型中的伤口愈合，并表明类肝素生物聚合物构成了一类具有广泛潜在用途的新型组织修复剂。这种方法在愈合受损与疾病（如糖尿病）相关的情况下的有效性仍有待确定。
