Abstract:For three-dimensional tissue engineering scaffolds, the major challenges of hydrogels are poor mechanical integrity and difficulty in handling during implantation. In contrast, electrospun scaffolds provide tunable mechanical properties and high porosity; but, are limited in cell encapsulation. To overcome these limitations, we developed a “hybrid nanosack” by combination of a peptide amphiphile (PA) nanomatrix gel and an electrospun poly (ε-caprolactone) (ePCL) nanofiber sheet with porous crater-like structur… Show more
“…Delivery of FGF-2 and VEGF along with the heparin-binding PA nanomatrix gel demonstrated improved islet viability and function along with enhanced angiogenesis. For in vivo application of a PA nanomatrix gel, a bio-inspired hybrid nanosack was developed by combining a PA nanomatrix gel and an electrospun poly (ε-caprolactone) (ePCL) nanofiber sheet with porous crater-like structures [ 59 ]. The PA nanomatrix gel provides an islet-nurturing environment, while the ePCL nanofiber sheet maintains the mechanical stability of the gel within the implant area.…”
Section: Reviewmentioning
confidence: 99%
“…In addition, the delivery of FGF-2 along with the crater-like structures of the ePCL nanofiber sheet synergistically benefited blood vessel formation in the hybrid nanosack when implanted into the rat omentum. Thus, the hybrid nanosack shows potential to be used as a bioartifical pancreas since it provides an islet-protective and nurturing environment along with enhanced angiogenesis in the implantation area [ 59 ]. Fig.…”
Pancreatic islet transplantation has been validated as a treatment for type 1 diabetes since it maintains consistent and sustained type 1 diabetes reversal. However, one of the major challenges in pancreatic islet transplantation is the body's natural immune response to the implanted islets. Immunosuppressive drug treatment is the most popular immunomodulatory approach for islet graft survival. However, administration of immunosuppressive drugs gives rise to negative side effects, and long-term effects are not clearly understood. A bioartificial pancreas is a therapeutic approach to enable pancreatic islet transplantation without or with minimal immune suppression. The bioartificial pancreas encapsulates the pancreatic islets in a semi-permeable environment which protects islets from the body's immune responses, while allowing the permeation of insulin, oxygen, nutrients, and waste. Many groups have developed various types of the bioartificial pancreas and tested their efficacy in animal models. However, the clinical application of the bioartificial pancreas still requires further investigation. In this review, we discuss several types of bioartificial pancreases and address their advantages and limitations. We also discuss recent advances in bioartificial pancreas applications with microfluidic or micropatterning technology.
“…Delivery of FGF-2 and VEGF along with the heparin-binding PA nanomatrix gel demonstrated improved islet viability and function along with enhanced angiogenesis. For in vivo application of a PA nanomatrix gel, a bio-inspired hybrid nanosack was developed by combining a PA nanomatrix gel and an electrospun poly (ε-caprolactone) (ePCL) nanofiber sheet with porous crater-like structures [ 59 ]. The PA nanomatrix gel provides an islet-nurturing environment, while the ePCL nanofiber sheet maintains the mechanical stability of the gel within the implant area.…”
Section: Reviewmentioning
confidence: 99%
“…In addition, the delivery of FGF-2 along with the crater-like structures of the ePCL nanofiber sheet synergistically benefited blood vessel formation in the hybrid nanosack when implanted into the rat omentum. Thus, the hybrid nanosack shows potential to be used as a bioartifical pancreas since it provides an islet-protective and nurturing environment along with enhanced angiogenesis in the implantation area [ 59 ]. Fig.…”
Pancreatic islet transplantation has been validated as a treatment for type 1 diabetes since it maintains consistent and sustained type 1 diabetes reversal. However, one of the major challenges in pancreatic islet transplantation is the body's natural immune response to the implanted islets. Immunosuppressive drug treatment is the most popular immunomodulatory approach for islet graft survival. However, administration of immunosuppressive drugs gives rise to negative side effects, and long-term effects are not clearly understood. A bioartificial pancreas is a therapeutic approach to enable pancreatic islet transplantation without or with minimal immune suppression. The bioartificial pancreas encapsulates the pancreatic islets in a semi-permeable environment which protects islets from the body's immune responses, while allowing the permeation of insulin, oxygen, nutrients, and waste. Many groups have developed various types of the bioartificial pancreas and tested their efficacy in animal models. However, the clinical application of the bioartificial pancreas still requires further investigation. In this review, we discuss several types of bioartificial pancreases and address their advantages and limitations. We also discuss recent advances in bioartificial pancreas applications with microfluidic or micropatterning technology.
“…Therefore, combination of PCL and chitosan is a widely accepted approach in the literature for novel tissue engineering scaffolds. 2,10 The electrospinning technique can also be combined with other fabrication methods and structures such as hydrogels, 11 sputtering/electrodeposition, 12 grafting, 5 freeze-drying, 6 dip-coating, 13 photo-crosslinking, 14 conventional melt-plotting 15 and cell sheet engineering 7 simultaneously or consecutively to obtain more complex structures with multiple components for advanced tissue scaffold applications.…”
In this study, dry air plasma jet and dielectric barrier discharge Ar + O or Ar + N plasma modifications and their effects on wettability, topography, functionality and biological efficiency of the hybrid polymeric poly (ε-caprolactone)/chitosan scaffolds were reported. The samples treated with Ar + O dielectric barrier discharge plasma (80 sccm O flow rate, 3-min treatment) or with dry air plasma jet (15-cm nozzle-sample distance, 13-min treatment) had the closest wettability (49.11 ± 1.83 and 53.60 ± 0.95, respectively) to the commercial tissue culture polystyrene used for cell cultivation. Scanning electron microscopy images and X-ray photoelectron spectrometry analysis showed increase in topographical roughness and OH/NH functionality, respectively. Increased fluid uptake capacity for the scaffolds treated with Ar + O dielectric barrier discharge plasma (73.60% ± 1.78) and dry air plasma jet (72.48% ± 0.75) were also noted. Finally, initial cell attachment as well as seven-day cell viability, growth and proliferation performances were found to be significantly better for both plasma treated scaffolds than for untreated scaffolds.
“…In addition, various bioactive peptide sequences, such as cell adhesive ligands and enzyme-mediated degradation sites, can be incorporated into the PA, which enables mimicry of essential properties of the natural extracellular matrix (ECM), a critical component in regulation of cell behaviors. ,,, Our previous study successfully demonstrated that islet encapsulation in the RGD peptide (cell adhesive ligand: arginine, glycine, and aspartic acid)-incorporated PA nanomatrix gel improved islet viability and function in vitro . For in vivo application of the PA nanomatrix gel to the omentum, an alternative extrahepatic islet transplantation site, our group also developed a hybrid nanosack by combination of a PA nanomatrix gel and an electrospun poly(ε-caprolactone) (ePCL) nanofiber sheet with craterlike structures. , In the omentum, the ePCL nanofiber sheet maintained the mechanical stability of the PA nanomatrix gel. In addition, angiogenic growth factor delivery (FGF-2) along with craterlike structures of the ePCL nanofiber sheet promoted blood vessel generation surrounding the hybrid nanosack in the omentum for sufficient supply of oxygen and nutrients .…”
Section: Introductionmentioning
confidence: 99%
“…For in vivo application of the PA nanomatrix gel to the omentum, an alternative extrahepatic islet transplantation site, our group also developed a hybrid nanosack by combination of a PA nanomatrix gel and an electrospun poly(ε-caprolactone) (ePCL) nanofiber sheet with craterlike structures. , In the omentum, the ePCL nanofiber sheet maintained the mechanical stability of the PA nanomatrix gel. In addition, angiogenic growth factor delivery (FGF-2) along with craterlike structures of the ePCL nanofiber sheet promoted blood vessel generation surrounding the hybrid nanosack in the omentum for sufficient supply of oxygen and nutrients . Therefore, the PA nanomatrix gel has great potential to serve as an ideal bioartificial pancreas which provides an ECM-mimicking, islet nurturing environment with a semipermeable immunoisolation barrier to enhance islet survival and function after islet transplantation.…”
The major concern of pancreatic islet transplantation is that the implanted islets are exposed to the immune system of the recipient. To overcome this challenge, the peptide amphiphile (PA) nanomatrix gel was used for immunoisolation of islets through microencapsulation. The PA can self-assemble to form a nanomatrix gel with an extracellular matrix-mimicking, islet nurturing microenvironment and a semipermeable immune barrier. In this study, the islet protective effect of the PA nanomatrix gel was evaluated by coculture of PA-encapsulated human islets with differentiated U937 cells (human monocyte cell-line) for 3 and 7 days. The coculture of the bare islets with the differentiated U937 cells stimulated proinflammatory cytokine (IL-1β and TNF-α) secretion and caused islet death after 7 days, which simulated an early inflammatory response environment after islet transplantation. The PA-encapsulated islets, however, did not stimulate proinflammatory cytokine secretion and maintained islet viability up to 7 days. More insulin-producing β cells were observed when islets were PA-encapsulated than control islets with the differentiated U937 cells for 7 days compared to the bare islets. This result was also confirmed by dithizone staining analysis. Further evaluation of islet functionality was assessed by a glucose-stimulated insulin secretion test. The PA-encapsulated islets showed greater insulin secretion response to glucose stimulation than the bare islets with the differentiated U937 cells after 3 and 7 days. These results demonstrated that islet encapsulation with the PA nanomatrix gel was able to improve islet survival and function in the presence of inflammatory responses, which will increase the success rate of islet engraftment and the efficacy of islet transplantation.
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