title: Porous polymer scaffold for on-site delivery of stem cells--Protects from oxidative stress and potentiates wound tissue repair.
abstract: 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-1β, TNF-α, 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.
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, India; Academy of Scientific & Innovative Research (AcSIR), 2 Rafi Marg, New Delhi 110 001, India.
authors.forename: Ramasatyaveni
authors.initials: R
authors.lastname: Geesala
authors.affiliation: Nanomaterials Laboratory, Division of Inorganic and Physical Chemistry, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, India; Academy of Scientific & Innovative Research (AcSIR), 2 Rafi Marg, New Delhi 110 001, India.
authors.forename: Nimai
authors.initials: N
authors.lastname: Bar
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, India; Academy of Scientific & Innovative Research (AcSIR), 2 Rafi Marg, New Delhi 110 001, India.
authors.forename: Neha R
authors.initials: NR
authors.lastname: Dhoke
authors.affiliation: Nanomaterials Laboratory, Division of Inorganic and Physical Chemistry, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, India; Academy of Scientific & Innovative Research (AcSIR), 2 Rafi Marg, New Delhi 110 001, India. Electronic address: pratyay@iict.res.in.
authors.forename: Pratyay
authors.initials: P
authors.lastname: Basak
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, India; Academy of Scientific & Innovative Research (AcSIR), 2 Rafi Marg, New Delhi 110 001, India. Electronic address: amitavadas@iict.res.in.
authors.forename: Amitava
authors.initials: A
authors.lastname: Das
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002374:Catalase / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D004987:Ethers / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008422:Materials Testing; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D011092:Polyethylene Glycols / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry*; D016062:Porosity; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D054457:Tissue Scaffolds / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014945:Wound Healing; D014947:Wounds and Injuries / Q000628:therapy*
chemical_list: D001672:Biocompatible Materials; D004987:Ethers; D007378:Interleukins; D011140:Polyurethanes; D014409:Tumor Necrosis Factor-alpha; C518220:poly(ethylene glycol) dimethyl ether; C000611574:polyethyleneglycol-polyurethane; D011092:Polyethylene Glycols; D003094:Collagen; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2
keywords: Anti-oxidant; Bone-marrow stem cells; Engraftment; Neo-vascularization; PEG–PU porous networks; Wound healing