The ability of photothermal biomaterials to convert light to heat can have diverse applications in medicine. However, the lack of effective biomaterials has adversely impacted progress and clinical translation in this promising field. The overall goal of this proposed research is to generate, characterize, and apply photothermal nanocomposites for effective tissue repair. In this approach, we will generate nanocomposites in which, gold nanorods are incorporated within biocompatible biomacromolecules including, elastin-like polypeptides (ELPs), collagen, fibrin and their blends. The photothermal response of these nanocomposites will be investigated using both, pulsed and continuous wavelength lasers at different power intensities. In addition, the mechanical properties and efficacy of laser-triggered drug (MMP inhibitor) delivery from these nanocomposites will be determined (Specific Aim 1). Nanocomposites with effective photothermal properties will be investigated for their ability to repair ruptured porcine intestinal tissue ex vivo; an incision model of tissue rupture will be investigated. Both pulsed and continuous lasers, at different power intensities, will be investigated in order to facilitate nanocomposite-mediated localized photothermal welding of the ruptured tissue. Tensile strength, leak pressure and burst pressure will be investigated in order to determine the mechanical integrity of the nanocomposite-repaired tissue. The efficacy of photothermal nanocomposites for preventing bacterial leakage from bacteria-rich intestinal lumen will also be investigated. Nanocomposite composition and operating conditions that result in the most effective recovery of tissue properties compared to intact tissue will be identified (Specific Aim 2). The most effective nanocomposite type and operating conditions will be further evaluated for maintaining tissue integrity and facilitating repair in a mouse model of colon leakage. Mechanical properties, including burst pressures, biochemical and immune responses, effect of MMP inhibitor delivery, and photothermal effects will be determined following in vivo welding. Longer-term survival studies will also be carried out (Specific Aim 3). It is anticipated that the current research will lead to transformative developments in both, fundamental studies as well as application of biocompatible photothermal nanocomposites for tissue repair. Findings from this research have very high potential for direct translation to several clinical applications that can benefit from the several advantages of photothermal tissue repair.

Public Health Relevance

This research involves the generation, characterization, and evaluation of photothermal nanocomposites for tissue repair. Elastin, collagen, fibrin and their blends will be employed in combination with gold nanorods leading to formation of the nanocomposites. The photothermal properties of these novel biomaterials will be exploited for facilitating tissue repair ex vivo and in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB020690-02
Application #
9139897
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Rampulla, David
Project Start
2015-09-09
Project End
2019-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Mushaben, Madaline; Urie, Russell; Flake, Tanner et al. (2018) Spatiotemporal modeling of laser tissue soldering using photothermal nanocomposites. Lasers Surg Med 50:143-152
Urie, Russell; Ghosh, Deepanjan; Ridha, Inam et al. (2018) Inorganic Nanomaterials for Soft Tissue Repair and Regeneration. Annu Rev Biomed Eng 20:353-374