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COLLAGEN MATRIX MODIFICATIONS IMPACT ON MATRIX MICROSTRUCTURE AND MASS TRANSPORT OF MACROMOLECULES

thesis
posted on 2022-12-07, 00:26 authored by Alexandra Lynn PlummerAlexandra Lynn Plummer

   

Subcutaneous injection is a biotherapeutic drug delivery method that is currently growing due to low cost, better patient compliance, minimally invasive, and the convenience that it can be done at home. Common injection sites for subcutaneous injection include the upper outer arms, abdomen, buttocks, and upper outer thigh. Heterogeneity of the tissue exists between and within each of these locations. The subcutaneous tissue space is made up of adipose tissue, proteins, collagen, and blood vessels and each of these components has an impact on the mass transport of the injected biotherapeutics and how they are absorbed into the vascular system and then distributed to the body. The current methods used to model the subcutaneous tissue space are either very expensive and not feasible for multiple repetitions, cannot incorporate fibrillar proteins or cellular components, or model a more homogeneous tissue space. These limitations do not allow for these models to accurately represent the subcutaneous tissue space. The engineering objective for this project was to develop a platform with tunable matrix architecture and biochemical composition for evaluating mass transport. This project utilizes collagen and the primary matrix due to the large abundance of collagen in the body.  We explored the effects that a change in polymerization temperature of the collagen and collagen concentration had on the fiber architecture and pore diameter. The results showed that higher polymerization temperatures of the collagen gels resulted in smaller fiber and pore diameters and an increase in concentration resulted in an increase in fiber volume fraction and a decrease in pore diameter. Fibronectin (FN) and hyaluronic acid (HA) were added to the collagen gels to analyze the impact on the structure of collagen gels with a change in polymerization temperature and collagen concentration. The addition of FN did not strongly alter the collagen fiber architecture between polymerization temperatures and collagen concentrations. Through staining and imaging, we saw an aggregation of FN around the collagen fibrils due to their opposing charges causing them to bind. The addition of HA had moderate impact on collagen fiber architecture across all polymerization temperatures and between collagen concentrations. The collagen + FN gels were used for the mass transport study. The results showed that there was little to no difference between the recovery rates of macromolecules of different charges and size between the collagen and collagen + FN gels, indicating that the transport of molecules through both of the collagen gels was impacted by a steric effect rather than an effect in charge.

  

Funding

Eli Lilly

History

Degree Type

  • Master of Science in Biomedical Engineering

Department

  • Biomedical Engineering

Campus location

  • West Lafayette

Advisor/Supervisor/Committee Chair

Dr. Luis Solorio

Additional Committee Member 2

Dr. Julie Liu

Additional Committee Member 3

Dr. Arezoo Ardekani

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