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Modeling and Validation of Multilayer Poly(Lactide-Co-Glycolide) Scaffolds for In Vitro Directed Differentiation of Juxtaposed Cartilage and Bone. - PubMed - NCBI
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Tissue Eng Part A. 2015 Aug;21(15-16):2228-40. doi: 10.1089/ten.TEA.2015.0089. Epub 2015 Jun 3.

Modeling and Validation of Multilayer Poly(Lactide-Co-Glycolide) Scaffolds for In Vitro Directed Differentiation of Juxtaposed Cartilage and Bone.

Huang GX1,2, Arany PR1,2,3,4, Mooney DJ1,2.

Author information

1
1 Harvard University School of Engineering and Applied Sciences , Cambridge, Massachusetts.
2
2 Wyss Institute for Biologically Inspired Engineering, Harvard University , Cambridge, Massachusetts.
3
3 Harvard School of Dental Medicine , Boston, Massachusetts.
4
4 National Institutes of Dental and Craniofacial Research, National Institutes of Health , Bethesda, Maryland.

Abstract

Polymeric scaffolds, which release growth factors in a temporally controlled manner, have successfully directed the differentiation of stem cells into monolithic tissues of a single lineage. However, engineering precise boundaries in multilineage functional tissues, such as the juxtaposed cartilaginous and osseous tissue present in articulated joints, often remains a challenge. This work demonstrates a precise materials system for in vitro reconstruction of the three-dimensional architecture of these types of human tissues. Multilayer poly(lactide-co-glycolide) (PLG) scaffolds were used to produce spatiotemporal gradients to direct the differentiation of an initially uniform population of mesenchymal stem cells (MSCs) into juxtaposed cartilage and bone. Specifically, growth factors (chondrogenic transforming growth factor-β3 and osteogenic bone morphogenetic protein-4) and their neutralizing antibodies were incorporated within distinct layers of the PLG scaffolds to create spatially segregated morphogen fields within the scaffold volume. The multilayer PLG scaffold designs were optimized by mathematical modeling, and generation of spatially segregated morphogen gradients was validated by assessing activity of luciferase reporter cell lines responsive to each growth factor. Scaffolds seeded with MSCs demonstrated production of juxtaposed cartilage and bone, as evaluated by biochemical staining and western blotting for tissue-specific matrix proteins. This work demonstrates a significant advance for the engineering of implantable constructs comprising tissues of multiple lineages, with potential applications in orthopedic regenerative medicine.

PMID:
25923238
PMCID:
PMC4529069
DOI:
10.1089/ten.TEA.2015.0089
[Indexed for MEDLINE]
Free PMC Article
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