Nagakura Takeshi, Hirata Hitoshi, Tsujii Masaya, Sugimoto Toshiko, Miyamoto Keiichi, Horiuchi Takashi, Nagao Masahiro, Nakashima Toshihide, Uchida Atsumasa
Department of Orthopaedic Surgery, Faculty of Medicine, Mie University, Tsu City, Japan.
Plast Reconstr Surg. 2005 Sep;116(3):831-8. doi: 10.1097/01.prs.0000176894.70848.98.
Alginates have a wide variety of potential clinical applications, including use in cell encapsulation, drug delivery, and tissue engineering. Although the compounds are typically used in the form of a calcium hydrogel, alginates in this form possess several disadvantages, including low biodegradability, induction of foreign body reactions, and cytotoxicity secondary to Ca2+ efflux and contamination with bioincompatible substances. Thus, the goal of the present study was to develop a new method of obtaining sterilized, pure, highly viscous alginate sol from seaweed alginates and to determine its utility as an injectable antiadhesion drug.
Viscous injectable pure alginate sol was produced from a commercially available sodium alginate, and its molecular and physical characteristics were analyzed. The biological properties of the viscous injectable pure alginate sol were analyzed using cultured fibroblasts prepared from the dorsal skin of neonatal rats to determine its biocompatibility and its effects on cell proliferation, cell migration, and collagen lattice contraction.
The mannuronic acid-to-glucuronic acid ratio of viscous injectable pure alginate sol, as determined by nuclear magnetic resonance studies, was 1.2, and its viscosity at 5 percent was 17,800 mPa. Purification used to produce viscous injectable pure alginate sol decreased contamination by insoluble particles by 20 percent and decreased polyphenol concentration by 17 percent. In vitro analyses with cultured fibroblasts demonstrated that viscous injectable pure alginate sol had excellent biodegradability and biocompatibility and that viscous injectable pure alginate sol inhibited fibroblast proliferation and migration. Furthermore, assessment of collagen contraction with floating fibroblast-loaded collagen lattices indicated that viscous injectable pure alginate sol enhanced wound healing in surrounding connective tissues.
The authors conclude that viscous injectable pure alginate sol can inhibit scar formation by presenting a physical barrier to invading fibroblasts and by enhancing wound healing of surrounding tissues.
海藻酸盐具有广泛的潜在临床应用,包括用于细胞封装、药物递送和组织工程。尽管这些化合物通常以钙水凝胶的形式使用,但这种形式的海藻酸盐存在几个缺点,包括低生物降解性、诱导异物反应以及由于Ca2+外流和生物不相容物质污染导致的细胞毒性。因此,本研究的目的是开发一种从海藻海藻酸盐中获得无菌、纯净、高粘性海藻酸盐溶胶的新方法,并确定其作为可注射抗粘连药物的效用。
从市售海藻酸钠制备粘性可注射纯海藻酸盐溶胶,并分析其分子和物理特性。使用从新生大鼠背部皮肤制备的培养成纤维细胞分析粘性可注射纯海藻酸盐溶胶的生物学特性,以确定其生物相容性及其对细胞增殖、细胞迁移和胶原晶格收缩的影响。
通过核磁共振研究确定,粘性可注射纯海藻酸盐溶胶的甘露糖醛酸与葡萄糖醛酸的比例为1.2,其5%时的粘度为17,800 mPa。用于生产粘性可注射纯海藻酸盐溶胶的纯化过程使不溶性颗粒的污染降低了20%,多酚浓度降低了17%。对培养成纤维细胞的体外分析表明,粘性可注射纯海藻酸盐溶胶具有优异的生物降解性和生物相容性,并且粘性可注射纯海藻酸盐溶胶抑制成纤维细胞的增殖和迁移。此外,用漂浮的负载成纤维细胞的胶原晶格评估胶原收缩表明,粘性可注射纯海藻酸盐溶胶可促进周围结缔组织的伤口愈合。
作者得出结论,粘性可注射纯海藻酸盐溶胶可通过对侵入的成纤维细胞形成物理屏障并促进周围组织的伤口愈合来抑制瘢痕形成。