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Injectable dual-gelling cell-laden composite hydrogels for bone tissue engineering

Abstract The present work investigated the osteogenic potential of injectable, dual thermally and chemically gelable composite hydrogels for mesenchymal stem cell (MSC) delivery in vitro and in vivo . Composite hydrogels comprising copolymer macromers of N -isopropylacrylamide were fabricated throug...

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Published in:Biomaterials 2016-03, Vol.83, p.1-11
Main Authors: Vo, T.N, Shah, S.R, Lu, S, Tatara, A.M, Lee, E.J, Roh, T.T, Tabata, Y, Mikos, A.G
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cited_by cdi_FETCH-LOGICAL-c608t-cb0e6b35d67ad948e6c3c05513a5b8cb08cb97ca7a06cf6c20698862c13927b83
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container_title Biomaterials
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creator Vo, T.N
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Mikos, A.G
description Abstract The present work investigated the osteogenic potential of injectable, dual thermally and chemically gelable composite hydrogels for mesenchymal stem cell (MSC) delivery in vitro and in vivo . Composite hydrogels comprising copolymer macromers of N -isopropylacrylamide were fabricated through the incorporation of gelatin microparticles (GMPs) as enzymatically digestible porogens and sites for cellular attachment. High and low polymer content hydrogels with and without GMP loading were shown to successfully encapsulate viable MSCs and maintain their survival over 28 days in vitro . GMP incorporation was also shown to modulate alkaline phosphatase production, but enhanced hydrogel mineralization along with higher polymer content even in the absence of cells. Moreover, the regenerative capacity of 2 mm thick hydrogels with GMPs only, MSCs only, or GMPs and MSCs was evaluated in vivo in an 8 mm rat critical size cranial defect for 4 and 12 weeks. GMP incorporation led to enhanced bony bridging and mineralization within the defect at each timepoint, and direct bone-implant contact as determined by microcomputed tomography and histological scoring, respectively. Encapsulation of both GMPs and MSCs enabled hydrogel degradation leading to significant tissue infiltration and osteoid formation. The results suggest that these injectable, dual-gelling cell-laden composite hydrogels can facilitate bone ingrowth and integration, warranting further investigation for bone tissue engineering.
doi_str_mv 10.1016/j.biomaterials.2015.12.026
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source ScienceDirect Freedom Collection
subjects Advanced Basic Science
Alkaline Phosphatase - metabolism
Animals
Biological Assay
Biomedical materials
Bone and Bones - diagnostic imaging
Bone and Bones - drug effects
Bone and Bones - physiology
Bones
Cells, Immobilized - cytology
Cells, Immobilized - drug effects
Cells, Immobilized - metabolism
Critical size cranial defect
Defects
Dentistry
Encapsulation
Gelatin - pharmacology
Gelatin microparticles
Hydrogels
Hydrogels - pharmacology
In vitro testing
Injections
Mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - drug effects
Microspheres
Mineralization
N-isopropylacrylamide
Rats, Inbred F344
Tissue engineering
Tissue Engineering - methods
X-Ray Microtomography
title Injectable dual-gelling cell-laden composite hydrogels for bone tissue engineering
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