Pancreatic islet transplantation (PIT) has been tried with consistent and sustained type 1 diabetes reversal. However, the substantial loss of islet cells during the peritransplant period which limits islet graft survival represents a major problem for practical implementation of PIT. Two significant factors associated with this problem are: 1) loss of natural islet extracellular matrix (ECM) microenvironment during islet isolation and 2) the inherent characteristics of particular surgical implantation site for PIT The goal of this proposalis to develop an innovative strategy to provide an ECM mimicking microenvironment that enhances islet survival, function, and engraftment in the omentum. Our proposed hybrid nanosack will serve as a clinically-applicable innovative strategy, as it will be designed for both reconstructing islet-ECM microenvironment and inducing islet revasculazation in the omentum. The hybrid nanosack will consist of 1) a self-assembled peptide amphiphile (PA) nanomatrix gel capable of encapsulating islets with a nurturing microenvironment and 2) a poly (?-caprolactone) electrospun (ePCL) nanofiber sheet with a craterlike porous structure for infiltration of blood vessels and a mechanically stable structure for surgical manipulation. Outcomes from this proposal will support feasibility of the hybrid nanosack for enhanced islet engraftments in the omuntum through following two Specific Aims.
Specific Aim 1 : To demonstrate enhanced survival and function of islets encapsulated in a self-assembled peptide amphiphile nanomatrix gel in vitro.
Specific Aim 2 : To fabricate a hybrid nanosack for extrahepatic islet transplantation and determine revascularization around the omentum in vivo.
Type 1 diabetes has a significant societal impact through long-term complications including kidney failure, blindness, nerve damage, and cardiovascular problems. The goal of this proposal is to develop an innovative strategy to enhance islet survival, function, and engraftment in the omentum to treat type I diabetes.
|Hwang, Patrick T J; Lim, Dong-Jin; Fee, Timothy et al. (2016) A bio-inspired hybrid nanosack for graft vascularization at the omentum. Acta Biomater 41:224-34|
|Alexander, Grant C; Vines, Jeremy B; Hwang, Patrick et al. (2016) Novel Multifunctional Nanomatrix Reduces Inflammation in Dynamic Conditions in Vitro and Dilates Arteries ex Vivo. ACS Appl Mater Interfaces 8:5178-87|
|Hwang, Patrick T J; Murdock, Kyle; Alexander, Grant C et al. (2016) Poly(?-caprolactone)/gelatin composite electrospun scaffolds with porous crater-like structures for tissue engineering. J Biomed Mater Res A 104:1017-29|
|Hwang, Patrick T J; Shah, Dishant K; Garcia, Jacob A et al. (2016) Progress and challenges of the bioartificial pancreas. Nano Converg 3:28|
|El-Ferzli, George T; Andukuri, Adinarayana; Alexander, Grant et al. (2015) A Nitric Oxide-Releasing Self-Assembled Peptide Amphiphile Nanomatrix for Improving the Biocompatibility of Microporous Hollow Fibers. ASAIO J 61:589-95|
|Gilbert, Shawn R; MacLennan, Paul A; Backstrom, Ian et al. (2015) Altered lower extremity fracture characteristics in obese pediatric trauma patients. J Orthop Trauma 29:e12-7|
|Kaushik, Sagar N; Scoffield, Jessica; Andukuri, Adinarayana et al. (2015) Evaluation of ciprofloxacin and metronidazole encapsulated biomimetic nanomatrix gel on Enterococcus faecalis and Treponema denticola. Biomater Res 19:9|
|Lim, Dong-Jin; Andukuri, Adinarayana; Vines, Jeremy B et al. (2014) Enhanced MIN-6 beta cell survival and function on a nitric oxide-releasing peptide amphiphile nanomatrix. Int J Nanomedicine 9 Suppl 1:13-21|
|Andukuri, Adinarayana; Min, IlJae; Hwang, Patrick et al. (2014) Evaluation of the effect of expansion and shear stress on a self-assembled endothelium mimicking nanomatrix coating for drug eluting stents in vitro and in vivo. Biofabrication 6:035019|