Hong Hyo-Jeong, Jin Su-Eon, Park Jeong-Sook, Ahn Woong Shick, Kim Chong-Kook
Laboratory of Excellency for Drug and Gene Delivery, College of Pharmacy, Seoul National University, 599 Kwanangno, Kwanak-gu, Seoul 151-742, Republic of Korea.
Biomaterials. 2008 Dec;29(36):4831-7. doi: 10.1016/j.biomaterials.2008.08.023. Epub 2008 Sep 30.
Smad3 mediates the intracellular signaling of TGF-beta1 superfamily and plays a critical role in the cellular proliferation, differentiation and elaboration of matrix pivotal to cutaneous wound healing. Smad3 antisense oligonucleotides (ASOs) impregnated polyelectrolyte complex (PEC) containing chitosan and sodium alginate was prepared for accelerated wound healing. Physicochemical properties of PEC were characterized by zeta potential, scanning electron microscopy and bioadhesive test. Full-thickness, excisional wounds were made on the dorsum of C57BL6 mice. Then, smad3 ASOs-PEC, PEC alone, smad3 ASOs and gauze dressing were applied to determine concentration of TGF-beta1 and collagen in tissues and observe the wound contraction and histology of tissues. Zeta potentials and bioadhesive strengths of ASOs-PEC were increased as the chitosan ratio in PEC. In smad3 ASOs-PEC, the healing process suggested by wound closure and histological observation was faster than other groups because collagen contents increased and level of TGF-beta1 decreased. These results demonstrate that the smad3 ASOs-PEC composed of chitosan and sodium alginate could be applied for accelerated wound healing.
Smad3介导TGF-β1超家族的细胞内信号传导,并在细胞增殖、分化以及对皮肤伤口愈合至关重要的基质形成过程中发挥关键作用。制备了负载Smad3反义寡核苷酸(ASOs)的含壳聚糖和海藻酸钠的聚电解质复合物(PEC),用于促进伤口愈合。通过zeta电位、扫描电子显微镜和生物黏附试验对PEC的物理化学性质进行了表征。在C57BL6小鼠背部制作全层切除伤口。然后,应用Smad3 ASOs-PEC、单独的PEC、Smad3 ASOs和纱布敷料,以测定组织中TGF-β1和胶原蛋白的浓度,并观察伤口收缩情况和组织的组织学变化。随着PEC中壳聚糖比例的增加,ASOs-PEC的zeta电位和生物黏附强度升高。在Smad3 ASOs-PEC组中,伤口闭合和组织学观察显示的愈合过程比其他组更快,因为胶原蛋白含量增加而TGF-β1水平降低。这些结果表明,由壳聚糖和海藻酸钠组成的Smad3 ASOs-PEC可用于加速伤口愈合。