Kirk James F, Ritter Gregg, Finger Isaac, Sankar Dhyana, Reddy Joseph D, Talton James D, Nataraj Chandra, Narisawa Sonoko, Millán José Luis, Cobb Ronald R
Research and Development Department; Nanotherapeutics, Inc.; Alachua, FL USA.
MLM Biologics; Gainesville, FL USA.
Biomatter. 2013 Oct-Dec;3(4). doi: 10.4161/biom.25633. Epub 2013 Jul 29.
Collagen scaffolds have been widely employed as a dermal equivalent to induce fibroblast infiltrations and dermal regeneration in the treatment of chronic wounds and diabetic foot ulcers. Cross-linking methods have been developed to address the disadvantages of the rapid degradation associated with collagen-based scaffolds. To eliminate the potential drawbacks associated with glutaraldehyde cross-linking, methods using a water soluble carbodiimide have been developed. In the present study, the glycosaminoglycan (GAG) hyaluronic acid (HA), was covalently attached to an equine tendon derived collagen scaffold using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) to create ntSPONGE The HA was shown to be homogeneously distributed throughout the collagen matrix. In vitro analyses of the scaffold indicated that the cross-linking enhanced the biological stability by decreasing the enzymatic degradation and increasing the thermal denaturation temperature. The material was shown to support the attachment and proliferation of mouse L929 fibroblast cells. In addition, the cross-linking decreased the resorption rate of the collagen as measured in an intramuscular implant model in rabbits. The material was also shown to be biocompatible in a variety of in vitro and in vivo assays. These results indicate that this cross-linked collagen-HA scaffold, ntSPONGE has the potential for use in chronic wound healing.
胶原蛋白支架已被广泛用作真皮替代物,以诱导成纤维细胞浸润和真皮再生,用于治疗慢性伤口和糖尿病足溃疡。人们已开发出交联方法来解决与基于胶原蛋白的支架相关的快速降解缺点。为了消除与戊二醛交联相关的潜在缺点,已开发出使用水溶性碳二亚胺的方法。在本研究中,使用1-乙基-3-(3-二甲基氨基丙基)碳二亚胺(EDC)将糖胺聚糖(GAG)透明质酸(HA)共价连接到马肌腱衍生的胶原蛋白支架上,制成ntSPONGE。结果表明,HA均匀分布在整个胶原蛋白基质中。对该支架的体外分析表明,交联通过降低酶促降解和提高热变性温度增强了生物稳定性。该材料被证明能支持小鼠L929成纤维细胞的附着和增殖。此外,在兔肌肉植入模型中测量发现,交联降低了胶原蛋白的吸收速率。在各种体外和体内试验中,该材料也显示出生物相容性。这些结果表明,这种交联的胶原蛋白-HA支架ntSPONGE具有用于慢性伤口愈合的潜力。