Design of biomaterials for cell-based therapies requires presentation of specific physical and chemical cues to cells, analogous to cues provided by native extracellular matrices (ECM). We previously identified a peptide sequence with high affinity towards apatite (VTKHLNQISQSY, VTK) using phage display. The aims of this study were to identify a human MSC-specific peptide sequence through phage display, combine it with the apatite-specific sequence, and verify the specificity of the combined dual-functioning peptide to both apatite and human bone marrow stromal cells.
View Article and Find Full Text PDFCell instructive mineralized biomaterials are a promising alternative to conventional auto-, allo-, and xenograft therapies for the reconstruction of critical sized defects. Extracellular matrix proteins, peptide domains, and functional motifs demonstrating cell and mineral binding activity have been used to improve cell attachment. However, these strategies vary in their tissue regeneration outcomes due to lack of specificity to both regenerative cell populations and the material substrates.
View Article and Find Full Text PDFWe demonstrate that rapamycin can induce regression of adenomatous polyposis coli (Apc) mutation-dependent colonic adenomas in genetically engineered mice (CPC;Apc). An endoscope was used to visualize adenomas in CPC;Apc mice weekly for 10 weeks. The lesion surface areas were measured using a distance gauge and digitally generated grid.
View Article and Find Full Text PDFGastrointestinal cancers are heterogeneous and can overexpress several protein targets that can be imaged simultaneously on endoscopy using multiple molecular probes. We aim to demonstrate a multispectral scanning fiber endoscope for wide-field fluorescence detection of colonic dysplasia. Excitation at 440, 532, and 635 nm is delivered into a single spiral scanning fiber, and fluorescence is collected by a ring of light-collecting optical fibers placed around the instrument periphery.
View Article and Find Full Text PDFObjective: To demonstrate a near-infrared (NIR) peptide that is highly specific for colonic adenomas on fluorescence endoscopy in vivo.
Design: A 3 mm diameter endoscope was adapted to deliver 671 nm illumination and collect NIR fluorescence (696-736 nm). Target (QPIHPNNM) and control (YTTNKH) peptides were labelled with Cy5.
We validate specific binding activity of a fluorescence-labeled peptide to colorectal dysplasia in living mice using a miniature, flexible, fiber microendoscope that passes through the instrument channel of an endoscope. The microendoscope delivers excitation light at 473 nm through a fiber-optic bundle with outer diameter of 680 µm to collect en face images at 10 Hz with 4 µm lateral resolution. We applied the FITC-labeled peptide QPIHPNNM topically to colonic mucosa in genetically engineered mice that spontaneously develop adenomas.
View Article and Find Full Text PDFColorectal cancer (CRC) is a major cause of cancer-related deaths in much of the world. Most CRCs arise from pre-malignant (dysplastic) lesions, such as adenomatous polyps, and current endoscopic screening approaches with white light do not detect all dysplastic lesions. Thus, new strategies to identify such lesions, including non-polypoid lesions, are needed.
View Article and Find Full Text PDFPersistent colonic inflammation increases risk for cancer, but mucosal appearance on conventional endoscopy correlates poorly with histology. Here we demonstrate the use of a flexible silver halide fiber to collect mid-infrared absorption spectra and an interval model to distinguish colitis from normal mucosa in dextran sulfate sodium treated mice. The spectral regime between 950 and 1800 cm(-1) was collected from excised colonic specimens and compared with histology.
View Article and Find Full Text PDFApatite-binding peptides discovered by phage display provide an alternative design method for creating functional biomaterials for bone and tooth tissue repair. A limitation of this approach is the absence of display peptide phosphorylation--a post-translational modification important to mineral-binding proteins. To refine the material specificity of a recently identified apatite-binding peptide, and to determine critical design parameters (net charge, charge distribution, amino acid sequence and composition) controlling peptide affinity for mineral, we investigated the effects of phosphorylation and sequence scrambling on peptide adsorption to four different apatites (bone-like mineral, and three types of apatite containing initially 0, 5.
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