Biomedical subjects

Jennie B Leach

Publications and source records attributed to Jennie B Leach.

4 recordsLinked to original sources

PubMed2007

Visualization of flow-aligned type I collagen self-assembly in tunable pH gradients.

Collagen is a major component of the extracellular matrix that exhibits unique hierarchical organization at multiple length scales ranging from nano to macroscale. Despite numerous methods to create collagen-based biomaterials, the self-assembly process of collagen ex vivo is poorly understood. Here, we describe a system that uses a microfluidic method to investigate the dynamics of collagen self-assembly. A main inlet stream of semidilute soluble collagen-I is hydrodynamically focused by two side inlet streams, which gradually increases the pH in the main stream. This enables dynamic nonequilibrium investigation of the self-assembly process simultaneously at different positions and therefore different stages in the assembly process within the same system. The device is designed for in situ monitoring and characterization of collagen assembly using polarization microscopy and X-ray diffraction: the continuous extensional flow provides highly ordered phases of the macromolecules over a large distance in the outlet microchannel and allows for data collection without material damage. We further demonstrate that finite element method simulations provide a good description of our experimental results regarding the diffusive phenomena, flow profile, and pH distribution. Our approach has broad impact, since it provides a powerful means of controlling and investigating the dynamic self-assembly process of biomacromolecules.

Animals↗

PubMed2005

Crosslinked alpha-elastin biomaterials: towards a processable elastin mimetic scaffold.

Elastin is a critical biochemical and biomechanical component of vascular tissue. However, elastin is also highly insoluble and therefore difficult to process into new biomaterials. We present a simple approach for synthesizing elastin-based materials from two commercially available and water-soluble components: alpha-elastin and a diepoxy crosslinker. Reaction pH was shown to modulate the degree of crosslinking, as demonstrated by materials characterized with a range of swelling ratios (approximately 10-25), enzymatic degradation rates (approximately 8-50% per h in 0.1 u/ml elastase), and elastic moduli (approximately 4-120 kPa). Crosslinking with a combination alkaline and neutral pH process results in materials with the highest degree of crosslinks, as indicated by a swelling ratio of 10, slow degradation rate, and high elastic moduli (approximately 120 kPa). Furthermore, the crosslinked alpha-elastin materials support vascular smooth muscle cell (VSMC) adhesion and a decreased proliferation rate compared to polystyrene controls. The functional outcomes of the crosslinking reaction, including the dependence of structure-function properties on reaction pH, are discussed. Our approach towards 'processable' elastin-based materials is versatile and could be integrated into existing tissue engineering methodologies to enhance biomaterial performance by providing a natural elastomeric and biofunctional component.

Animals↗

PubMed2005

Characterization of protein release from photocrosslinkable hyaluronic acid-polyethylene glycol hydrogel tissue engineering scaffolds.

The goal of this work was to utilize the naturally derived bioactive polymer hyaluronic acid (HA) to create a combination tissue engineering scaffold and protein delivery device. HA is a non-immunogenic, non-adhesive glycosaminoglycan that plays significant roles in several cellular processes, including angiogenesis and the regulation of inflammation. In previous work, we created photopolymerizable glycidyl methacrylate-hyaluronic acid (GMHA) hydrogels that had controlled degradation rates, were cytocompatible, and were able to be modified with peptide moieties. In the present studies, we characterized the release of a model protein, bovine serum albumin (BSA), from GMHA and GMHA-polyethylene glycol (PEG) hydrogels. Although BSA could be released rapidly (> 60% within 6 h) from 1% GMHA hydrogels, we found that increasing either the GMHA or the PEG concentrations could lengthen the duration of protein delivery. Preliminary size exclusion chromatography studies indicated that the released BSA was almost entirely in its native monomeric form. Lastly, protein release was extended to several weeks by suspending BSA-poly(lactic-co-glycolic acid) microspheres within the hydrogel bulk. These initial studies indicate that the naturally derived biopolymer HA can be employed to design novel photopolymerizable composites that are suitable for delivering stable proteins from scaffolding in tissue engineering applications.

Coated Materials, Biocompatible↗

PubMed2004

Development of photocrosslinkable hyaluronic acid-polyethylene glycol-peptide composite hydrogels for soft tissue engineering.

Hyaluronic acid (HA; also called hyaluronan) is a naturally derived, nonimmunogenic, nonadhesive glycosaminoglycan that has important roles in several wound-healing processes. In previous work, we created photocrosslinkable glycidyl methacrylate-HA (GMHA) hydrogel biomaterials that were cytocompatible, biologically active, and had a decreased rate of hyaluronidase degradation compared with native HA. The goal of the studies presented herein was to explore peptide conjugation techniques to further adjust the material and biological properties of the GMHA hydrogels. We conjugated GMHA with acrylated forms of polyethylene glycol (PEG) and PEG-peptides to yield GMHA-PEG-peptide composite hydrogels. By varying the reactant concentrations, we created stable hydrogels with high peptide conjugation efficiencies (up to 80%), controllable peptide concentrations (in the range of 1-6 micromol peptide per milliliter of hydrogel), and defined physicochemical properties (e.g., swelling ratio, enzymatic degradation rate). These composite hydrogels may prove to be a promising scaffolding biomaterial for a variety of soft tissue engineering applications.

Chemical Phenomena↗