Bio-synthetic materials for immunomodulation of islet transplants

Foster, Gregory D.; Garcı́a, Andrés J.

doi:10.1016/j.addr.2017.05.012

Cited by 27 publications

(18 citation statements)

References 82 publications

(87 reference statements)

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“…A high PEG concentration of 20% was used to fabricate the microporous hydrogel to improve mechanical robustness for potential clinical use, which may alter crosslinking density and thus substrate stiffness (DeForest and Anseth, 2012). However, isolated islets have been shown to survive and function on or within a wide range of polymeric biomaterial substrates with varying stiffness both in vitro and in vivo in numerous studies (Apeldoorn, 2015; Buitinga et al, 2013; Foster and García, 2017; Graham et al, 2013; Pedraza et al, 2013; Phelps et al, 2013; Smink et al, 2017).…”

Section: 5 Discussionmentioning

confidence: 99%

Evaluation of encapsulating and microporous nondegradable hydrogel scaffold designs on islet engraftment in rodent models of diabetes

Rios

Skoumal

Liu

et al. 2018

Biotech & Bioengineering

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Islet transplantation is a promising therapeutic option for type 1 diabetes mellitus, yet the current delivery into the hepatic portal vasculature is limited by poor engraftment. Biomaterials have been used as a means to promote engraftment and function at extrahepatic sites, with strategies being categorized as encapsulation or microporous scaffolds that can either isolate or integrate islets with the host tissue, respectively. Although these approaches are typically studied separately using distinct material platforms, herein, we developed nondegradable polyethylene glycol (PEG)-based hydrogels for islet encapsulation or as microporous scaffolds for islet seeding to compare the initial engraftment and function of islets in syngeneic diabetic mice. Normoglycemia was restored with transplantation of islets within either encapsulating or microporous hydrogels containing 700 islet equivalents (IEQ), with transplantation on microporous hydrogels producing lower blood glucose levels at earlier times. A glucose challenge test at 1 month after transplant indicated that encapsulated islets had a delay in glucose-stimulated insulin secretion, whereas microporous hydrogels restored normoglycemia in times consistent with native pancreata. Encapsulated islets remained isolated from the host tissue, whereas the microporous scaffolds allowed for revascularization of the islets after transplant. Finally, we compared the inflammatory response after transplantation for the two systems and noted that microporous hydrogels had a substantially increased presence of neutrophils. Collectively, these findings suggest that both encapsulation and microporous PEG scaffold designs allow for stable engraftment of syngeneic islets and the ability to restore normoglycemia, yet the architecture influences islet function and responsiveness after transplantation.

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Section: 5 Discussionmentioning

confidence: 99%

Evaluation of encapsulating and microporous nondegradable hydrogel scaffold designs on islet engraftment in rodent models of diabetes

Rios

Skoumal

Liu

et al. 2018

Biotech & Bioengineering

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show abstract

“…Poly(ethylene glycol) (PEG)-based gels, another commonly used encapsulation material, are less immunogenic, non-ionic polymers, and are stable at physiological conditions [181]. Variation in the molecular weight of the PEG polymer can be used to control protein adsorption and permeability of the membrane by adjusting the porosity [182].…”

Section: Islet Encapsulationmentioning

confidence: 99%

“…Materials which are used for encapsulation are also capable carriers for inhibitors of local inflammation [181]. The cytokine transforming growth factor-β (TGFβ) [198] and chemokine CXCL12 [199,200] have been locally delivered in encapsulation materials to suppress the inflammatory response.…”

Section: Islet Encapsulationmentioning

confidence: 99%

Chemical Strategies for Improving Islet Transplant Outcomes

Quintana¹,

Stinchcomb²,

Kostyo³

et al. 2018

obm transplant

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Islet transplantation has proven to be a viable treatment for individuals suffering from both Type 1 Diabetes Mellitus (T1D) and chronic pancreatitis. However, a variety of challenges limit the effectiveness of this procedure by reducing the number of islets that survive the harvesting and transplantation processes. Increasing islet survival would increase the longterm effectiveness of the procedure and allow this technique to be used in more patients. A number of factors have been shown to improve the outcomes of pancreatic islet transplantation, including immunological suppression and prevention of coagulation. In this review, we will discuss various chemical strategies reported in the literature for the preservation of islet graft function after transplantation, including islet encapsulation, the adoption of anti-inflammatory and immune suppressing molecules, and islet surface modification.

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“…Such strategies include assembling a thin layered PEG-lipid structure around the surface of islets and assembling a multilayer film around islets using biotin and streptavidin [48]. It has been recently demonstrated that the simple PEGylation of islets provided modest immunoprotection in full MHC mismatched mice [42].…”

Section: Biomaterials In Transplantationmentioning

confidence: 99%

Physical Protection of Pancreatic Islets for Transplantation

Lee¹,

Sathialingam²,

Alexander³

et al. 2018

Biomaterials - Physics and Chemistry - New Edition

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Type 1 diabetes is an autoimmune disorder that destroys the insulin producing cells of the pancreas. The mainstay of treatment is replacement of insulin through injectable exogenous insulin. Improvements in islet isolation techniques and immunosuppression regimens have made islet transplants a treatment options for select patients. Islet transplants have improved graft function over the years, however, graft function beyond year two is rare and notably these patients require immunosuppression to prevent rejection. Cell encapsulation has been proposed for numerous cell types but it has found increasing enthusiasm for islets. Since islet transplants have experienced a myriad of success the next step is to improve graft function and avoid systemically toxic immunosuppressive regimens. Cell encapsulation hopes to accomplish this goal. Encapsulation involves encasing cells in a semipermeable biocompatible hydrogel that allows the passage of nutrients and oxygen however blocks immune regulators from destroying the cell thus avoiding systemic drugs. Several advances in encapsulation engineering and cell viability promises to make this a revolutionary discovery. In this chapter, we will provide a review of islet encapsulation as used for the treatment of type 1 diabetes.

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Bio-synthetic materials for immunomodulation of islet transplants

Cited by 27 publications

References 82 publications

Evaluation of encapsulating and microporous nondegradable hydrogel scaffold designs on islet engraftment in rodent models of diabetes

Evaluation of encapsulating and microporous nondegradable hydrogel scaffold designs on islet engraftment in rodent models of diabetes

Chemical Strategies for Improving Islet Transplant Outcomes

Physical Protection of Pancreatic Islets for Transplantation

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