title: A transient cell-shielding method for viable MSC delivery within hydrophobic scaffolds polymerized in situ.
abstract: Cell-based therapies have emerged as promising approaches for regenerative medicine. Hydrophobic poly(ester urethane)s offer the advantages of robust mechanical properties, cell attachment without the use of peptides, and controlled degradation by oxidative and hydrolytic mechanisms. However, the application of injectable hydrophobic polymers to cell delivery is limited by the challenges of protecting cells from reaction products and creating a macroporous architecture post-cure. We designed injectable carriers for cell delivery derived from reactive, hydrophobic polyisocyanate and polyester triol precursors. To overcome cell death caused by reaction products from in situ polymerization, we encapsulated bone marrow-derived stem cells (BMSCs) in fastdegrading, oxidized alginate beads prior to mixing with the hydrophobic precursors. Cells survived the polymerization at >70% viability, and rapid dissolution of oxidized alginate beads after the scaffold cured created interconnected macropores that facilitated cellular adhesion to the scaffold in vitro. Applying this injectable system to deliver BMSCs to rat excisional skin wounds showed that the scaffolds supported survival of transplanted cells and infiltration of host cells, which improved new tissue formation compared to both implanted, pre-formed scaffolds seeded with cells and acellular controls. Our design is the first to enable injectable delivery of settable, hydrophobic scaffolds where cell encapsulation provides a mechanism for both temporary cytoprotection during polymerization and rapid formation of macropores post-polymerization. This simple approach provides potential advantages for cell delivery relative to hydrogel technologies, which have weaker mechanical properties and require incorporation of peptides to achieve cell adhesion and degradability.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA; Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Ruijing
authors.initials: R
authors.lastname: Guo
authors.affiliation: US Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Ward
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA; Research Service, VA Tennessee Valley Healthcare System, Nashville, TN, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Davidson
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Duvall
authors.affiliation: US Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wenke
authors.affiliation: Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA; Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA. Electronic address: scott.guelcher@vanderbilt.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Guelcher
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004867:Equipment Design; D019544:Equipment Failure Analysis; D048091:Guided Tissue Regeneration / Q000295:instrumentation*; D057927:Hydrophobic and Hydrophilic Interactions; D022125:Lacerations / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000295:instrumentation* / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D011108:Polymers / Q000138:chemical synthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000293:injuries / Q000473:pathology; D054457:Tissue Scaffolds
chemical_list: D011108:Polymers
keywords: Cell encapsulation; Mesenchymal stem cell; Polymerisation; Polyorthoester; Polyurethane; Wound healing