Abstract
Platelet-derived growth factor (PDGF) exerts multiple cellular effects that stimulate wound repair in multiple tissues. However, a major obstacle for its successful clinical application is the delivery system, which ultimately controls the in vivo release rate of PDGF. Polylactic-co-glycolic acid (PLGA) microspheres (MS) in nanofibrous scaffolds (NFS) have been shown to control the release of rhPDGF-BB in vitro. In order to investigate the effects of rhPDGF-BB release from MS in NFS on gene expression and enhancement of soft tissue engineering, rhPDGF-BB was incorporated into differing molecular weight (MW) polymeric MS. By controlling the MW of the MS over a range of 6.5 KDa–64 KDa, release rates of PDGF can be regulated over periods of weeks to months in vitro. The NFS-MS scaffolds were divided into multiple groups based on MS release characteristics and PDGF concentration ranging from 2.5–25.0 µg and evaluated in vivo in a soft tissue wound repair model in the dorsa of rats. At 3, 7, 14 and 21 days post-implantation, the scaffold implants were harvested followed by assessments of cell penetration, vasculogenesis and tissue neogenesis. Gene expression profiles using cDNA microarrays were performed on the PDGF-releasing NFS. The percentage of tissue invasion into MS-containing NFS at 7 days was higher in the PDGF groups when compared to controls. Blood vessel number in the HMW groups containing either 2.5 or 25 µg PDGF was increased above those of other groups at 7d (p<0.01). Results from cDNA array showed that PDGF strongly enhanced in vivo gene expression of the CXC chemokine family members such as CXCL1, CXCL2 and CXCL5. Thus, sustained release of rhPDGF-BB, controlled by slow-releasing MS associated with the NFS delivery system, enhanced cell migration and angiogenesis in vivo, and may be related to an induced expression of chemokine-related genes. This approach offers a technology to accurately control growth factor release to promote soft tissue engineering in vivo.
Highlights
Growth factors are essential for cellular signaling for migration, proliferation, differentiation, and maturation.[1]
Based on the finding that polymers with high molecular weight (HMW) degrade more slowly than those with low molecular weight (LMW), the in vivo release of growth factor embedded in microspheres is controlled by molecular weight,[22] which is different from the traditional simple coating method in which the release rate of growth factors depends on physico-chemical interactions between the adsorbed growth factors and scaffold surfaces
Did the nanofibrous scaffolds (NFS) become larger in volume than their original shape, and the porous structure of scaffolds appeared irregular and distorted, in contrast to the groups without Platelet derived growth factor (PDGF) encapsulated by MS
Summary
Growth factors are essential for cellular signaling for migration, proliferation, differentiation, and maturation.[1] the development of an effective delivery system that integrates appropriate scaffolds and growth factors for specific tissue repair and regeneration presents a clinical challenge. [2] Recently, nanofibrous scaffolds with controlled-release growth factors have shown significant potential for tissue engineering applications.[3]. [5] PDGF participates in embryonic development of organs such as kidney, heart, and vasculature, [6] and plays a very important role in postnatal tissue repair, regeneration and disease development. [17] These results are in part because PDGF promotes collagen synthesis, recruits mural cells through neovessels and regulates maturation of the infarct vasculature. Based on the finding that polymers with high molecular weight (HMW) degrade more slowly than those with low molecular weight (LMW), the in vivo release of growth factor embedded in microspheres is controlled by molecular weight,[22] which is different from the traditional simple coating method in which the release rate of growth factors depends on physico-chemical interactions between the adsorbed growth factors and scaffold surfaces
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