Modified alginates provide a long-term disguise against the foreign body response

Bray, Natasha

doi:10.1038/nrd.2016.41

Cited by 4 publications

(5 citation statements)

References 2 publications

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“…alginate hydrogels (30,43), which makes the capsules more functionally durable and easier to retrieve. However, common retrieval techniques such as aspiration and lavage are time-consuming, and it is a great challenge to ensure complete retrieval given the large capsule number and the complicated organ structures inside the peritoneal space (8,18,32).…”

Section: Discussionmentioning

confidence: 99%

“…Next, we investigated the biocompatibility of TRAFFIC. In cell encapsulation, the biocompatibility of the encapsulating material is one of the most important factors; foreign body reactioninduced fibrosis can negatively affect the mass transfer and the viability of encapsulated cells (42,43). In recent years, much progress has been made on the biocompatibility of alginate materials, including both purity and formulation (25,30).…”

Section: Characterizations Of the Mechanical Robustness Mass Transfer Property And Biocompatibilitymentioning

confidence: 99%

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Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes

Chiu

Flanders

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

163

164

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Cell encapsulation has been shown to hold promise for effective, long-term treatment of type 1 diabetes (T1D). However, challenges remain for its clinical applications. For example, there is an unmet need for an encapsulation system that is capable of delivering sufficient cell mass while still allowing convenient retrieval or replacement. Here, we report a simple cell encapsulation design that is readily scalable and conveniently retrievable. The key to this design was to engineer a highly wettable, Ca-releasing nanoporous polymer thread that promoted uniform in situ cross-linking and strong adhesion of a thin layer of alginate hydrogel around the thread. The device provided immunoprotection of rat islets in immunocompetent C57BL/6 mice in a short-term (1-mo) study, similar to neat alginate fibers. However, the mechanical property of the device, critical for handling and retrieval, was much more robust than the neat alginate fibers due to the reinforcement of the central thread. It also had facile mass transfer due to the short diffusion distance. We demonstrated the therapeutic potential of the device through the correction of chemically induced diabetes in C57BL/6 mice using rat islets for 3 mo as well as in immunodeficient SCID-Beige mice using human islets for 4 mo. We further showed, as a proof of concept, the scalability and retrievability in dogs. After 1 mo of implantation in dogs, the device could be rapidly retrieved through a minimally invasive laparoscopic procedure. This encapsulation device may contribute to a cellular therapy for T1D because of its retrievability and scale-up potential.

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Section: Discussionmentioning

confidence: 99%

Section: Characterizations Of the Mechanical Robustness Mass Transfer Property And Biocompatibilitymentioning

confidence: 99%

Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes

Chiu

Flanders

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

163

164

View full text Add to dashboard Cite

show abstract

“…The fibrotic cellular overgrowth after long-term implantation in large-animal models or human patients is another major challenge for clinical applications. Given our mouse studies, which suggest that the NICE device supported long-term function of allogeneic cells even in presence of cellular overgrowth, it remains to be investigated what amount of fibrotic deposition may be permissible for cellular function in higher-order animals or human patients and whether additional fibrosis-mitigating coatings (18) may be applicable to improve device function.…”

Section: Discussionmentioning

confidence: 99%

“…Alginate microcapsule-based encapsulation systems have been extensively investigated and proven functional in multiple animal models (15)(16)(17)(18)(19)(20)(21). However, it is becoming increasingly recognized that the impossibility to ensure complete graft retrieval will hinder their application for SC- cell delivery in clinical settings.…”

Section: Introductionmentioning

confidence: 99%

A nanofibrous encapsulation device for safe delivery of insulin-producing cells to treat type 1 diabetes

et al. 2021

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Transplantation of stem cell–derived β (SC-β) cells represents a promising therapy for type 1 diabetes (T1D). However, the delivery, maintenance, and retrieval of these cells remain a challenge. Here, we report the design of a safe and functional device composed of a highly porous, durable nanofibrous skin and an immunoprotective hydrogel core. The device consists of electrospun medical-grade thermoplastic silicone-polycarbonate-urethane and is soft but tough (~15 megapascal at a rupture strain of >2). Tuning the nanofiber size to less than ~500 nanometers prevented cell penetration while maintaining maximum mass transfer and decreased cellular overgrowth on blank (cell-free) devices to as low as a single-cell layer (~3 micrometers thick) when implanted in the peritoneal cavity of mice. We confirmed device safety, indicated as continuous containment of proliferative cells within the device for 5 months. Encapsulating syngeneic, allogeneic, or xenogeneic rodent islets within the device corrected chemically induced diabetes in mice and cells remained functional for up to 200 days. The function of human SC-β cells was supported by the device, and it reversed diabetes within 1 week of implantation in immunodeficient and immunocompetent mice, for up to 120 and 60 days, respectively. We demonstrated the scalability and retrievability of the device in dogs and observed viable human SC-β cells despite xenogeneic immune responses. The nanofibrous device design may therefore provide a translatable solution to the balance between safety and functionality in developing stem cell–based therapies for T1D.

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“…When these spheres were used to encapsulate b cells that were then transplanted into a diabetic mouse model system, islets were better able to survive and retain their functionality. [13][14][15] In a similar effort to reduce the immune-mediated rejection of sodium alginate hydrogels, Noverraz et al 16 developed a ketoprofen-grafted alginate hydrogel, which they found to reduce fibrosis and enhance encapsulated b cell functionality for at least 30 days after transplantation.…”

Section: Alginate Hydrogelsmentioning

confidence: 99%

Hydrogel materials for the application of islet transplantation

Guo

Huang

et al. 2019

J Biomater Appl

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Type 1 diabetes mellitus is a serious disease comprising approximately 10% of all diabetes cases, and the global incidence of type 1 diabetes mellitus is steadily rising without any promise of a cure in the near future. Although islet transplantation has proven to be an effective means of treating type 1 diabetes mellitus and promoting insulin independence in patients, its widespread implementation has been severely constrained by instances of post-transplantation islet cell death, rejection, and severe adverse immune responses. Islet encapsulation is an active area of research aimed at shielding implanted islets from immunological rejection and inflammation while still allowing for effective insulin and nutrient exchange with donor cells. Given their promising physical and chemical properties, hydrogels have been a major subject of focus in the field of islet transplantation and encapsulation technology, offering promising advances towards immunologically privileged islet implants. The present review therefore summarizes the current state of research regarding the use of hydrogels in the context of islet transplantation, including both natural molecular hydrogels and artificial polymer hydrogels, with the goal of understanding the current strengths and weaknesses of this treatment strategy.

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Modified alginates provide a long-term disguise against the foreign body response

Cited by 4 publications

References 2 publications

Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes

Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes

A nanofibrous encapsulation device for safe delivery of insulin-producing cells to treat type 1 diabetes

Hydrogel materials for the application of islet transplantation

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