Molecular substrate design for the selective adhesion, proliferation and differentiation of marrow connective tissue progenitors

A multi-faceted approach was applied to the molecular design of substrates for the selective adhesion, proliferation and differentiation of connective tissue progenitors (CTPs) from human bone marrow aspirates. The basic premise of the thesis is that integrin-specific adhesion peptides, when presented in a biophysically appropriate spatial arrangement against an inert background, allow enrichment of CTPs in vitro. Comb copolymer comprising a methyl methacrylate backbone with 10-mer poly(oxyethylene) sidechains was selected as the vehicle to present small adhesion peptides at the surface. This polymer shows excellent performance in cell resistance studies and offers sufficient functionalizable sites to create high local densities of ligands. Methods for preparing comb copolymer substrates with peptides in [approx.] 300 nm² clusters with inter-ligand spacings closer than integrins were developed. This nanometer-scale clustered presentation was favorable to integrin binding. Cells were more spread on RGD peptide substrates with a higher degree of nanoscale clustering but of the same overall peptide surface density as comparable substrates with lower degree of peptide clustering. We evaluated adhesion peptides for their ability to support CFU formation of marrow-derived CTPs using colony forming unit (CFU) assay.

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Au, Ada

Advisor dc:contributor.advisor

• Linda Griffith.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/33870

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/33870