Jin Qiming, Ma Peter X, Giannobile William V
Department of Periodontics and Oral Medicine, Michigan Center for Oral Health Research, School of Dentistry, University of Michigan, Ann Arbor, Michigan.
Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan ; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan.
Adv Skin Wound Care. 2010 Jan 1;1:375-381.
Platelet-derived growth factor (PDGF) is a multifunctional growth factor that exerts its biological effects on cellular chemotaxis, proliferation, matrix synthesis, antiapoptosis, and vascularization. PDGF is clinically approved to treat neuropathic diabetic ulcers and osseous defects due to periodontal disease.
The short half-life of PDGF limits the efficacy of its biological functions. Solving this problem remains a key obstacle for PDGF clinical application. Therefore, the development of an optimized controlled release delivery system offers significant potential.
BASIC/CLINICAL SCIENCE ADVANCES: In this article, we highlight the development of a polymeric delivery system of nanofibrous scaffolds containing PDGF-encapsulated microspheres for tissue engineering. The designed scaffolds were evaluated in a subcutaneous implantation model for tissue neogenesis, vascularization, and chemokine gene expression, as well as soft-tissue repair. PDGF was found to strongly upregulate gene expression of the CXC chemokine family members such as CXC chemokine ligand , , and that are important in angiogenesis, inflammation, and wound repair.
Recombinant human PDGF is approved by the Food and Drug Administration for patients afflicted with diabetic foot ulcers or compromised periodontal wounds. Challenges related to the transient biological activity of bolus PDGF administration using currently available release systems continue. Thus, it is necessary to explore new delivery systems to optimize biological activity and bioavailability of tissue growth factors.
The use of a controlled, "dial-able" delivery system allows for a more tightly regulated release of factors to promote repair of soft- and hard-tissue defects for clinical application.
血小板衍生生长因子(PDGF)是一种多功能生长因子,对细胞趋化性、增殖、基质合成、抗凋亡和血管生成具有生物学作用。PDGF在临床上被批准用于治疗神经性糖尿病溃疡和牙周病导致的骨缺损。
PDGF的半衰期短限制了其生物学功能的有效性。解决这一问题仍然是PDGF临床应用的关键障碍。因此,开发优化的控释递送系统具有巨大潜力。
基础/临床科学进展:在本文中,我们重点介绍了一种用于组织工程的含PDGF封装微球的纳米纤维支架聚合物递送系统的开发。在皮下植入模型中对设计的支架进行了组织新生、血管生成、趋化因子基因表达以及软组织修复方面的评估。发现PDGF能强烈上调CXC趋化因子家族成员如CXC趋化因子配体1、2和7的基因表达,这些成员在血管生成、炎症和伤口修复中很重要。
重组人PDGF已被美国食品药品监督管理局批准用于患有糖尿病足溃疡或牙周伤口受损的患者。使用现有释放系统进行大剂量PDGF给药时,其短暂生物活性相关的挑战依然存在。因此,有必要探索新的递送系统,以优化组织生长因子的生物活性和生物利用度。
使用可控的“可调节”递送系统能够更严格地控制因子释放,以促进软组织和硬组织缺损的修复,用于临床应用。