期刊
ACS APPLIED BIO MATERIALS
卷 5, 期 10, 页码 4581-4588出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.2c00186
关键词
tumor microenvironment; bacterial collagen; hyaluronic acid; hydrogel; extracellular matrix
资金
- Australian Research Council [FT180100417, DP190101892]
- National Health and Medical Research Council (NHMRC) [APP1185021]
- National Cancer Institute of the National Institutes of Health [R01CA251443]
- Australian Research Council [FT180100417] Funding Source: Australian Research Council
This study demonstrates the production of a recombinant bacterial collagen-like protein (CLP) for thiol-ene pairing to norbornene functionalized hyaluronic acid (NorHA). The resulting hydrogel material shows adjustable modulus and strain-stiffening behavior similar to natural tumor matrices. It also exhibits good biocompatibility and can control cell adhesion, proliferation, and invasive properties of breast adenocarcinoma cells.
Laboratory models of the tumor microenvironment require control of mechanical and biochemical properties to ensure accurate mimicry of patient disease. In contrast to pure natural or synthetic materials, hybrid approaches that pair recombinant protein fragments with synthetic scaffolding show many advantages. Here we demonstrate production of a recombinant bacterial collagen-like protein (CLP) for thiol-ene pairing to norbornene functionalized hyaluronic acid (NorHA). The resultant hydrogel material shows an adjustable modulus with evidence for strain-stiffening behavior that resembles natural tumor matrices. Cysteine terminated peptide binding motifs are incorporated to adjust the cell-adhesion points. The modular hybrid gel shows good biocompatibility and was demonstrated to control cell adhesion, proliferation, and the invasive properties of MCF7 and MD-MBA-231 breast adenocarcinoma cells. The ease in which multiple structural and bioactive components can be integrated provides a robust framework to form models of the tumor microenvironment for fundamental studies and drug development.
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