A Versatile Microencapsulation Platform for Hyaluronic Acid and Polyethylene Glycol

Harrington, Stephen; Ott, Lindsey; Karanu, Francis; Ramachandran, Karthik; Stehno‐Bittel, Lisa

doi:10.1089/ten.tea.2019.0286

Cited by 18 publications

(24 citation statements)

References 37 publications

(42 reference statements)

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“…We have characterized fully the PEGDA formulation utilized here in previous publications showing the monodispersity, swelling ratio, diffusion characteristics and rheology [ 38 ]. In addition, we compared the results of transplants using encapsulated and unencapsulated canine islets into mice [ 21 ]. In addition, initial indications of a minimum effective dose were determined.…”

Section: Discussionmentioning

confidence: 99%

“…However, our viability and purity values were within the acceptable range published by the Collaborative Islet Transplant Registry for humans with ranges [ 49 ]. Canine islets are notoriously difficult to isolate from the pancreas [ 21 , 44 ] due partly to their small size (Tables 1 and 2 ) and low cell density ( Fig 1A ), resulting in lower initial viabilities after isolation. It is possible that factors released from dead or dying cells could attribute to some of the fibrosis noted in the surrounding tissue after transplantation, which is why the study in healthy dogs was conducted.…”

Section: Discussionmentioning

confidence: 99%

“…PEGDA microspheres were manufactured following our previously published Core Shell Spherification (CSS) protocol [ 21 ]. Briefly, PEGDA hydrogel precursor solution was prepared by dissolving PEGDA 3,400 and 20,000 (Laysan Bio, Inc.) at 18% and 12% (w/w), respectively, in a buffer containing 100 mM calcium chloride, 10 mM HEPES, and 0.025% (w/v) Irgacure 2959 followed by filtering through a 0.22-mm syringe.…”

Section: Methodsmentioning

confidence: 99%

“…Diacrylated PEG (PEGDA) is a biocompatible, slow-hardening hydrogel that can be used as a replacement to alginate. PEGDA has advantages because the precursors are widely available and inexpensive with appropriate diffusion characteristics [ 21 , 22 ]. In different formulations, the base chemistry (PEG) has been used to protect islets from immune rejection in multiple studies [ 23 – 25 ].…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, because of the slow gelation properties of PEGDA [ 26 ], it could not be formulated as microspheres except when produced using emulsion techniques, which can be harmful to cells. Manufacturing utilizing Core Shell Spherification provides a new technology that expands the number and types of hydrogel precursors that can be formed into microspheres [ 21 ]. In this study, we encapsulated canine islets in PEGDA microspheres and characterized the cells and the microspheres.…”

Section: Introductionmentioning

confidence: 99%

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PEGDA microencapsulated allogeneic islets reverse canine diabetes without immunosuppression

Harrington¹,

Karanu²,

Ramachandran³

et al. 2022

PLoS ONE

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Background Protection of islets without systemic immunosuppression has been a long-sought goal in the islet transplant field. We conducted a pilot biocompatibility/safety study in healthy dogs followed by a dose-finding efficacy study in diabetic dogs using polyethylene glycol diacrylate (PEGDA) microencapsulated allogeneic canine islets. Methods Prior to the transplants, characterization of the canine islets included the calculations determining the average cell number/islet equivalent. Following measurements of purity, insulin secretion, and insulin, DNA and ATP content, the islets were encapsulated and transplanted interperitoneally into dogs via a catheter, which predominantly attached to the omentum. In the healthy dogs, half of the microspheres injected contained canine islets, the other half of the omentum received empty PEGDA microspheres. Results In the biocompatibility study, healthy dogs received increasing doses of cells up to 1.7 M cells/kg body weight, yet no hypoglycemic events were recorded and the dogs presented with no adverse events. At necropsy the microspheres were identified and described as clear with attachment to the omentum. Several of the blood chemistry values that were abnormal prior to the transplants normalized after the transplant. The same observation was made for the diabetic dogs that received higher doses of canine islets. In all diabetic dogs, the insulin required to attempt to control blood glucose was cut by 50–100% after the transplant, down to no required insulin for the course of the 60-day study. The dogs had no adverse events and behavioral monitoring suggested normal activity after recovery from the transplant. Conclusions and implications The study provides evidence that PEGDA microencapsulated canine islets reversed the signs of diabetes without immunosuppression and led to states of insulin-independence or significantly lowered insulin requirements in the recipients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PEGDA microencapsulated allogeneic islets reverse canine diabetes without immunosuppression

Harrington¹,

Karanu²,

Ramachandran³

et al. 2022

PLoS ONE

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Advances in high throughput cell culture technologies for therapeutic screening and biological discovery applications

Ryoo,

Kimmel,

Rondo

et al. 2023

Bioengineering & Transla Med

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Cellular phenotypes and functional responses are modulated by the signals present in their microenvironment, including extracellular matrix (ECM) proteins, tissue mechanical properties, soluble signals and nutrients, and cell–cell interactions. To better recapitulate and analyze these complex signals within the framework of more physiologically relevant culture models, high throughput culture platforms can be transformative. High throughput methodologies enable scientists to extract increasingly robust and broad datasets from individual experiments, screen large numbers of conditions for potential hits, better qualify and predict responses for preclinical applications, and reduce reliance on animal studies. High throughput cell culture systems require uniformity, assay miniaturization, specific target identification, and process simplification. In this review, we detail the various techniques that researchers have used to face these challenges and explore cellular responses in a high throughput manner. We highlight several common approaches including two‐dimensional multiwell microplates, microarrays, and microfluidic cell culture systems as well as unencapsulated and encapsulated three‐dimensional high throughput cell culture systems, featuring multiwell microplates, micromolds, microwells, microarrays, granular hydrogels, and cell‐encapsulated microgels. We also discuss current applications of these high throughput technologies, namely stem cell sourcing, drug discovery and predictive toxicology, and personalized medicine, along with emerging opportunities and future impact areas.

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Advances in polymer‐based cell encapsulation and its applications in tissue repair

Xia

Chen

2023

Biotechnology Progress

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Cell microencapsulation is a more widely accepted area of biological encapsulation.In most cases, it involves fixing cells in polymer scaffolds or semi-permeable hydrogel capsules, providing the environment for protecting cells, allowing the exchange of nutrients and oxygen, and protecting cells against the attack of the host immune system by preventing the entry of antibodies and cytotoxic immune cells. Hydrogel encapsulation provides a three-dimensional (3D) environment similar to that experienced in vivo, so it can maintain normal cellular functions to produce tissues similar to those in vivo. Embedded cells can be genetically modified to release specific therapeutic products directly at the target site, thereby eliminating the side effects of systemic treatments. Cellular microcarriers need to meet many extremely high standards regarding their biocompatibility, cytocompatibility, immunoseparation capacity, transport, mechanical, and chemical properties. In this article, we discuss the biopolymer gels used in tissue engineering applications and the brief introduction of cell encapsulation for therapeutic protein production. Also, we review polymer biomaterials and methods for preparing cell microcarriers for biomedical applications. At the same time, in order to improve the application performance of cell microcarriers in vivo, we also summarize the main limitations and improvement strategies of cell encapsulation. Finally, the main applications of polymer cell microcarriers in regenerative medicine are summarized.

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A Versatile Microencapsulation Platform for Hyaluronic Acid and Polyethylene Glycol

Cited by 18 publications

References 37 publications

PEGDA microencapsulated allogeneic islets reverse canine diabetes without immunosuppression

PEGDA microencapsulated allogeneic islets reverse canine diabetes without immunosuppression

Advances in high throughput cell culture technologies for therapeutic screening and biological discovery applications

Advances in polymer‐based cell encapsulation and its applications in tissue repair

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