Zhiyong Xia

Structure and properties of collagen vitrigel membranes for ocular repair and regeneration applications

The frequency of ocular injuries on the battlefield has been steadily increasing during recent conflicts. Combat-related eye injuries are difficult to treat and solutions requiring donor tissue are not ideal and are often not readily available. Collagen vitrigels have previously been developed for corneal reconstruction, but increased transparency and mechanical strength are desired for improved vision and ease of handling. In this study, by systematically varying vitrification temperature, relative humidity and time, the collagen vitrigel synthesis conditions were optimized to yield the best combination of high transparency and high mechanical strength. Optical, mechanical, and thermal properties were characterized for each set of conditions to evaluate the effects of the vitrification parameters on material properties. Changes in denaturing temperature and collagen fibril morphology were evaluated to correlate properties with structure. Collagen vitrigels with transmittance up to 90%, tensile strength up to 12 MPa, and denaturing temperatures that significantly exceed the eye/body temperature have been synthesized at 40 °C and 40% relative humidity for one week. This optimal set of conditions enabled improvements of 100% in tensile strength and 11% in transmittance, compared to the previously developed collagen vitrigels.

Liquid-Filled Metal Microcapsules

A moisture-sensitive diisocyanate liquid is microencapsulated within a metal shell measuring less than 2 μm thick and 50 μm in diameter. This mild synthesis takes place through a series aqueous processing steps that occur at or near room temperature. Through a combination of emulsification, interfacial polymerization, and electroless plating, one can microencapsulate moisture- or air-sensitive chemicals within a metal seal. The liquid-filled metal microcapsules promise a number of advantages compared to conventional polymeric microencapsulation, including improved mechanical properties and improved barrier properties to gases and organic molecules.

Robust Composite-Shell Microcapsules via Pickering Emulsification

Microencapsulation technology has been increasingly applied toward the development of self-healing paints. Added to paint as a dry powder prior to spraying, the microcapsules store a liquid that can repair the protective barrier layer if released into a scratch. However, self-healing will not occur unless the microcapsules can withstand spray-painting, aggressive solvents in the paint, and long-term exposure to the elements. We have therefore developed a one-pot synthesis for the production of Pickering microcapsules with outstanding strength, solvent resistance, and barrier properties. Octadecyltrimethoxysilane-filled (OTS) microcapsules form via standard interfacial polycondensation, except that silica nanopowder (10-20 nm diameter) replaces the conventional surfactant or hydrocolloid emulsifier. Isophorone diisocyanate (IPDI) in the OTS core reacts with diethylenetriamine, polyethylenimine, and water to form a hard polymer shell along the interface. Compared to pure polyurea, the silica-polyurea composite improves the shelf life of the OTS by 10 times. The addition of SiO2 prevents leaching of OTS into xylenes and hexanes for up to 80 days, and the resulting microcapsules survive nebulization through a spray gun at 620 kPa in a 500 cSt fluid.

Synthesis and properties of regenerated cellulose-based hydrogels with high strength and transparency for potential use as an ocular bandage

Cellulose is a biologically derived material with excellent wound-healing properties. The high strength of cellulose fibers and the ability to synthesize gels with high optical transparency make these materials suitable for ocular applications. In this study, cellulose materials derived from wood pulp, cotton, and bacterial sources were dissolved in lithium chloride/N,N-dimethylacetamide to form regenerated cellulose hydrogels. Material properties of the resulting hydrogels, including water content, optical transparency, and tensile and tear strengths, were evaluated. Synthesis parameters, including activation time, dissolution time, relative humidity, and cellulose concentration, were found to impact the material properties of the resulting hydrogels. Overnight activation time improves the optical transparency of the hydrogels from 77% to 97% at 550 nm, whereas controlling cellulose concentration improves their tear strength by as much as 200%. On the basis of the measured transmittance and strength values of the regenerated hydrogels prepared via the optimized synthesis parameters, Avicel PH 101, Sigma-Aldrich microcrystalline cellulose 435236, and bacterial cellulose types were prioritized for future biocompatibility testing and potential clinical investigation.

Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells

Obtaining vascular smooth muscle tissue with mature, functional elastic fibers is a key obstacle in tissue-engineered blood vessels. Poor elastin secretion and organization leads to a loss of specialization in contractile smooth muscle cells, resulting in over proliferation and graft failure. In this study, human induced-pluripotent stem cells (hiPSCs) were differentiated into early smooth muscle cells, seeded onto a hybrid poly(ethylene glycol) dimethacrylate/poly (l-lactide) (PEGdma-PLA) scaffold and cultured in a bioreactor while exposed to pulsatile flow, towards maturation into contractile smooth muscle tissue. We evaluated the effects of pulsatile flow on cellular organization as well as elastin expression and assembly in the engineered tissue compared to a static control through immunohistochemistry, gene expression and functionality assays. We show that culturing under pulsatile flow resulted in organized and functional hiPSC derived smooth muscle tissue. Immunohistochemistry analysis revealed hiPSC-smooth muscle tissue with robust, well-organized cells and elastic fibers and the supporting microfibril proteins necessary for elastic fiber assembly. Through qRT-PCR analysis, we found significantly increased expression of elastin, fibronectin, and collagen I, indicating the synthesis of necessary extracellular matrix components. Functionality assays revealed that hiPSC-smooth muscle tissue cultured in the bioreactor had an increased calcium signaling and contraction in response to a cholinergic agonist, significantly higher mature elastin content and improved mechanical properties in comparison to the static control. The findings presented here detail an effective approach to engineering elastic human vascular smooth muscle tissue with the functionality necessary for tissue engineering and regenerative medicine applications. STATEMENT OF SIGNIFICANCE Obtaining robust, mature elastic fibers is a key obstacle in tissue-engineered blood vessels. Human induced-pluripotent stem cells have become of interest due to their ability to supplement tissue engineered scaffolds. Their ability to differentiate into cells of vascular lineages with defined phenotypes serves as a potential solution to a major cause of graft failure in which phenotypic shifts in smooth muscle cells lead to over proliferation and occlusion of the graft. Herein, we have differentiated human induced-pluripotent stem cells in a pulsatile flow bioreactor, resulting in vascular smooth muscle tissue with robust elastic fibers and enhanced functionality. This study highlights an effective approach to engineering elastic functional vascular smooth muscle tissue for tissue engineering and regenerative medicine applications.

Banded structures in collagen vitrigels for corneal injury repair.

There is a growing interest in using collagen vitrigels for corneal injury repair. We recently reported the synthesis and thermal denaturation behavior of these gels. In this paper, the banded structure in these vitrified gels is studied by small-angle X-ray scattering (SAXS) one-dimensional (1-D) correlation function analysis and transmission electron microscopy (TEM). Results demonstrate that the collagen vitrigel possess banded structures similar to those of the starting type I collagen, with an average D-spacing of 64nm (by SAXS) or 57nm (by TEM). A combination of SAXS 1-D correlation function analyses and TEM show that overlap and gap distances ranged from 30 to 33nm and from 23 to 25nm, respectively. Changing the vitrification condition does not impact on the banded structure significantly.

Effect of High Aspect Ratio Fillers on the Performance of Styrene-Butadiene Rubber

ABSTRACT Among the many material performance properties of vulcanized elastomers for tire tread application, rolling resistance and wet traction are particularly important since both greatly impact fuel efficiency and traction of a vehicle. Rolling resistance and wet traction are generally negatively correlated, i.e., with the increase in rolling resistance of a tire, its wet traction decreases. Silica nanofillers are often used for achieving the desired balance of wet traction and rolling resistance. However, the high cost of silica limits its wide spread application. In this research we studied the effects of using fillers with different aspect ratios (calculated by dividing the long dimension of a filler by its short dimension) on the performance of vulcanized styrene butadiene rubber (SBR), a common rubber for tire tread application. Three high aspect ratio fillers were used: aragonite calcium carbonate, wollastonite and carbon nanofiber. For comparison purpose, spherical silica filler was also included. We found that the high aspect ratio fillers were efficient in improving the wet traction and rolling resistance as well as enhancing the mechanical energy dissipation of SBR. Among the three high aspect ratio fillers studied, wollastonite provided the best wet traction and rolling resistance balance due to its high aspect ratio and compatibility with the base rubber. The effects of fillers induced crosslinking on the dynamic performance were also discussed.