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Collagen Nanoyarns: Hierarchical Three-Dimensional Biomaterial Constructs

Friday, December 17, 2021

2:00 PM-4:00 PM

BIOMED PhD Research Proposal

Collagen Nanoyarns: Hierarchical Three-Dimensional Biomaterial Constructs
Chukwuemeka Chikelu, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Caroline Schauer, PhD
Department of Materials Science and Engineering (MSE)
Margaret C. Burns Chair in Engineering
Associate Dean, Research and Faculty Affairs
Office of the Dean

Lin Han, PhD
Associate Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Rotator cuff tendon (RCT)  disorders, among musculoskeletal problems, are noteworthy because of their preponderance in the elderly, and the high surgical failure rates in cases presenting with massive tears. Surgical strategies include the augmentation of the repair site mechanically by various graft materials, with autografts and allografts being the main options for the restoration and repair of damaged tendons. However, challenges such as immune rejection and donor site morbidity among others still exist. Synthetic grafts, on the other hand,  are limited by poor cell adhesion, induced chronic inflammation and foreign body giant cell reaction.

Electrospun nanoscale fibers have attracted interest in tissue engineering because of their high surface-to-volume ratio, tunable diameter and pore size, and a microstructure that can replicate the topography of the tendon ECM. Collagen, the main protein and load-bearing structure of connective tissues, is considered the ideal scaffold biomaterial because of its inherent biocompatibility and non-inflammatory properties. However, the use of cytotoxic solvents and the typical 2D, mat-based geometry of electrospun collagen scaffolds render them inadequate for 3D tissue reconstruction and augmentation. Also, low porosity of the electrospun nanofibrous scaffolds hampers cell infiltration and restricts tissue formation to the scaffold surface. To solve these issues, investigators have used a modified electrospinning setup to generate twisted 3D nanofiber yarns that may be stretched for increased axial fiber alignment, a departure from the typical two-dimensional-(2D)-mat products of regular electrospinning. They also have electrospun nanofiber composites comprising distinct nanofibers of a desired polymer as well as a sacrificial polymer whose removal then increases the porosity of the remnant nanofiber scaffold. However, these methods have yet to be applied in the generation of 3D type I collagen nanoyarn scaffolds with tuned porosity.

The central hypothesis of this proposal is that Type I collagen nanoyarns used as biomimetic scaffolds can replicate the topography of the tendon ECM, thus regulating native cell response. We will test this hypothesis within 3 specific aims: fabricating collagen nanoyarns (CNY) by the nanoyarn-electrospinning of collagen solution; tuning CNY porosity by the inclusion, and subsequent removal, of sacrificial PEO nanofibers; and enhancing the mechanical integrity of CNY scaffolds by crosslinking and twisting/braiding while observing the response of cells cultured on the scaffolds in vitro. Aligned collagen scaffolds support differentiation by providing a uniformly-aligned substrate topographically akin to tendon ECM and is to be generated using the modified electrospinning setup.To tune porosity, an alternative nanofibrous yarn composite will be spun from collagen and PEO solutions with PEO as sacrificial nanofibers that would be removed in DI H2O after crosslinking collagen nanofiber components in GA vapor, and optimized scaffolds will be investigated for cell viability and morphological response by culturing cells and assessing adhesion, proliferation and morphological characteristics.

Contact Information

Natalia Broz

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