Qiming Jin1, Peter X Ma2, William V Giannobile3. 1. Department of Periodontics and Oral Medicine, Michigan Center for Oral Health Research, School of Dentistry, University of Michigan, Ann Arbor, Michigan. 2. 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. 3. Department of Periodontics and Oral Medicine, Michigan Center for Oral Health Research, School of Dentistry, University of Michigan, Ann Arbor, Michigan ; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan.
Abstract
BACKGROUND: 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 PROBLEM: The short half-life in vivo 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 in vivo gene expression of the CXC chemokine family members such as CXC chemokine ligand CXCL1, CXCL2, and CXCL5 that are important in angiogenesis, inflammation, and wound repair. CLINICAL CARE RELEVANCE: 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. CONCLUSION: 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.
BACKGROUND: 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 PROBLEM: The short half-life in vivo 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 in vivo gene expression of the CXC chemokine family members such as CXC chemokine ligand CXCL1, CXCL2, and CXCL5 that are important in angiogenesis, inflammation, and wound repair. CLINICAL CARE RELEVANCE: Recombinant humanPDGF 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. CONCLUSION: 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.
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