Author ORCID Identifier
0000-0002-4668-6971
Document Type
Dissertation
Date of Award
5-31-2022
Degree Name
Doctor of Philosophy in Biomedical Engineering - (Ph.D.)
Department
Biomedical Engineering
First Advisor
Vivek A. Kumar
Second Advisor
Pranela Rameshwar
Third Advisor
Dominic Pasquale Del Re
Fourth Advisor
Eun Jung Lee
Fifth Advisor
Jonathan M. Grasman
Abstract
According to the CDC, 15% of diabetic patients develop diabetic foot ulcers (DFU) and approximately 170,000 patients undergo non-traumatic amputation annually. DFU is a major complication of diabetes caused by non-healing full-thickness wounds through the dermis. The current treatments include blood sugar control, frequent debridement, offloading, moist wound care, infection treatment, and amputation. To achieve wound closure of DFU, appropriate wound care and antibiotic therapy are essential. Topical regimens include hydrocolloids, alginates, foam, silver-impregnated dressings, and hydrogels. Wound healing is a complex and dynamic interplay between the immune system, keratinocytes, and dermal cells (in case of cutaneous wound). Angiogenesis has long been known to be essential to guide tissue regeneration in the wound site. Recent work has highlighted the important role chemokines play in wound healing. Monocyte Chemoattractant Protein-1 (MCP-1), also known as C-C Motif Chemokine Ligand 2 (CCL2), is an inflammatory chemokine that regulates macrophage migration. MCP-1 is secreted by inflammatory, epithelial and endothelial cells. This results in enhanced cell proliferation and migration of monocytes, and natural killer cells to inflammatory regions. They secrete factors that destroy pathogens, phagocytose them, remove cellular debris, and secrete cytokines and chemokines integral to wound healing. Insufficient macrophage responses may impair wound healing processes in diabetic wounds. However, an imbalanced chemokine environment may prolong healing to a state of persistent hyperinflammation with an increase in inflammatory leukocytes. Self-assembling peptide hydrogel (SAPH) can be modified to include proangiogenic domains to promote in situ angiogenesis or an MCP-1 binding motif that can potentially modulate the healing of diabetic wounds/ulcers; due to the ability to chelate MCP-1 from the environment. It is hypothesized that an angiogenic SAPH or an inflammation modulatory SAPH can stimulate angiogenesis and regulate macrophage recruitment, thereby acting as scaffold support for wound healing. The objective of this work is to develop bioactive scaffolds for angiogenic and immune modulation, with potential use in the treatment of DFU. This is achieved through the following specific aims: 1) evaluate SAP in a diabetic wound healing model; 2) design and characterize immunomodulating SAP; and 3) evaluate in vivo properties and optimize design.
Recommended Citation
Kim, Ka-Kyung, "Design of self-assembled peptides for wound healing" (2022). Dissertations. 1875.
https://digitalcommons.njit.edu/dissertations/1875
Included in
Alternative and Complementary Medicine Commons, Biomedical Engineering and Bioengineering Commons
