Date of Award

Summer 8-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Molecular Science and Nanotechnology

First Advisor

David K Mills

Abstract

Human adipose stem cells (hASCs) provide a research tool for regenerative medicine in various capacities. There are major research needs for new therapies for bone-related diseases such as osteoporosis, osteomyelitis, and severe trauma. Human ASCs can self-renew for extended durations outside of the body and provide an ideal platform to study therapeutics for the formation of bone-specific modalities or wound healing applications.

Combining hASCs with nanomaterials is a growing area of research that requires additional studies. Halloysites (HNTs) are hollow aluminosilicate nanotubes with an exterior negative charge and a positively charged lumen. HNTs have demonstrated biocompatibility in cell and animal-based studies, with additional capabilities for vacuum loading of drugs and coating metal ions such as silver, zinc, strontium, and copper (mHNTs). Metal ions provide synergistic antimicrobial effects on prokaryotes, allowing healthy cells to form in infection risk areas. These unique properties allow a varying of methods to be developed in cell-based therapeutics at the tissue level.

The primary focus of my research is to investigate the therapeutic potential of metalized HNTs with a linked tripeptide known as GHK (glycyl-L-histidyl-L-lysine). GHK is known to be essential in the wound healing process. Ultimately, studying these interactions will lead to better bandages to be hemostatic, alleviate pain and inflammation, and cost-effectively possess antimicrobial features. Bone and wound analysis studies were conducted on hASCs after the incorporation of such nanoparticles. Results introducing GHK with metalized HNTs showed increased proliferation of hASCs, collagen production, and an increase in the genes ki67 and runx2, a proliferation and bone marker, respectively. Strontium-coated HNTs increased osteochondral differentiation after analysis by phase-contrast imaging, gene expression, and unique morphological changes of hASCs exhibiting trabecular-like bone formations in culture.

Copper-coated HNTs coupled with GHK increased wound closure after artificial wound analysis, further validating gene expression and proliferation studies. Human ASCs were additionally encapsulated in alginate hydrogels with GHK and mHNTs that increased cell viability and collagen production, leading to differentiated fibroblast clusters within the hydrogel constructs. Given these results, expanding the use of mHNTs with GHK in animal wound healing studies can profoundly impact wound healing if incorporated into FDA-approved materials.

Download

Share

COinS