Journal
BIOMATERIALS
Volume 77, Issue -, Pages 1-13Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.11.003
Keywords
Bone-marrow stem cells; PEG-PU porous networks; And-oxidant; Engraftment; Neo-vascularization; Wound healing
Funding
- CSIR-Mayo Clinic for Innovation and Translational Research [CMPP-07]
- CSIR, Ministry of Science and Technology, Government of India [CSC-0111]
- CSIR [CSC-0134, BSC-0112]
- UGC
- CSIR
- ICMR
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Wound healing by cell transplantation techniques often suffer setbacks due to oxidative stress encountered at injury sites. A porous polyethyleneglycol polyurethane (PEG-PU) scaffold that facilitates cell delivery and boosts tissue repair was developed through semi-interpenetrating polymer network approach. The key physico-chemical properties assessed confirms these polymeric matrices are highly thermostable, barostable, degrade at an acidic pH (5.8), biodegradable, cytocompatible and possess excellent porosity. Mechanism of cellular penetration into porous polymer networks was evident by a >= 6 - fold increase in gene expression of MMP-13 and MMP-2 via activation of Akt and Erk. H2O2-induced apoptosis of mouse bone marrow stem cells (BMSCs) was abrogated in presence of polymer networks indicating a protective effect from oxidative stress. Transplantation of BMSC + PEG-PU at murine excisional splint wound site depicted significant increase in fibroblast proliferation, collagen deposition, anti-oxidant enzyme activities of catalase, SOD and GPx. Furthermore it significantly decreased expression of pro-inflammatory cytokines (IL-1 beta, TNF-alpha, IL-8, etc) with a concomitant increase in anti-inflammatory cytokines (IL-10, IL-13) at an early healing period of day 7. Finally, immunostaining revealed an enhanced engraftment and vascularity indicating an accelerated wound tissue closure. This pre-clinical study demonstrates the proof-of-concept and further necessitates their clinical evaluation as potential cell delivery vehicle scaffolds. (C) 2015 Elsevier Ltd. All rights reserved.
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