Porous polymer scaffold for on-site delivery of stem cells - Protects from oxidative stress and potentiates wound tissue repair

Ramasatyaveni Geesala, Nimai Bar, Neha R. Dhoke, Pratyay Basak, Amitava Das

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalBiomaterials
Volume77
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
AD acknowledges the funding provided by “ CSIR-Mayo Clinic for Innovation and Translational Research , CMPP-07 ” and CSIR , Ministry of Science and Technology, Government of India , XIIth Five-year Plan Project # CSC-0111 . PB acknowledges CSIR funding for projects CSC-0134 and BSC-0112 . Fellowships provided by UGC, CSIR and ICMR are gratefully acknowledged by RG (UGC-SRF), NB (CSIR-SRF) and ND (ICMR-SRF). We also thank the technical assistance provided by Mr. Suresh Y in assisting the Flow-cytometry analysis. A provisional patent vide application No. 3470/DEL/2015 has been filed for the use of PEG-PU scaffold as stem cell delivery vehicle.

Publisher Copyright:
© 2015 Elsevier Ltd.

Keywords

  • Anti-oxidant
  • Bone-marrow stem cells
  • Engraftment
  • Neo-vascularization
  • PEG-PU porous networks
  • Wound healing

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