Hyaluronic Acid Hydrogel Microspheres for Slow Release Stem Cell Delivery

Hamilton, Megan; Harrington, Stephen; Dhar, Prajnaparamita; Stehno‐Bittel, Lisa

doi:10.1021/acsbiomaterials.1c00658

Cited by 27 publications

(29 citation statements)

References 51 publications

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“…The results of the pilot biocompatibility and efficacy studies described here validate the use of PEGDA microspheres as an encapsulant to protect allogeneic cells from immune destruction, while allowing secretion of insulin from the cells to normalize blood glucose values. 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 ].…”

Section: Discussionmentioning

confidence: 99%

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%

PEGDA microencapsulated allogeneic islets reverse canine diabetes without immunosuppression

Harrington¹,

Karanu²,

Ramachandran³

et al. 2022

PLoS ONE

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“…HA is a natural glycosaminoglycan believed to function as both a filler and a scaffold that provides support for cell ingrowth 113 . Furthermore, the transplantation of cells in hydrogels is thought to result in long‐term protection of the cells in vivo 114 . From obtained lipoaspirate, SVF was isolated and subsequently ASCs were cultured and added to HA.…”

Section: Fat Grafting Therapies For Lichen Sclerosusmentioning

confidence: 99%

“…113 Furthermore, the transplantation of cells in hydrogels is thought to result in long-term protection of the cells in vivo. 114 From obtained lipoaspirate, SVF was isolated and subsequently ASCs were cultured and added to HA. Application of ASC-HA solution into the subcutaneous plane of labia minora resulted in pain reduction and improvement of sexual function in all patients, which was assessed using the validated FSFI questionnaire.…”

Section: Combination Therapy Of Ascs With Hyaluronic Acid (Ha)mentioning

confidence: 99%

Autologous lipoaspirate as a new treatment of vulvar lichen sclerosus: A review on literature

Sluis

Scheers

Krenning

et al. 2022

Experimental Dermatology

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Lichen sclerosus (LS) is a chronic inflammatory dermatosis that mostly affects the genital and anal skin areas. LS can be asymptomatic or accompanied by symptoms, for example progressive pruritis, pain, sexual dysfunction and thus, a reduced quality of life (QoL). 1,2 LS occurs at all ages and in both sexes, whereby the male-to-female ratio ranges between 1:3 and 1:10. The exact prevalence is unclear; however, vulvar LS has been found to affect one in 70 women presenting to a general gynaecology practice. 1 The incidence of histologically proven LS in women was 14.6 per 100.000 woman-years in 2011 in the Netherlands. Noticeably, approximately 5% of all women affected by LS will develop vulvar squamous cell carcinoma, for which both LS and differentiated vulvar intraepithelial neoplasia (dVIN) are additional risk factors. 3,4 Although the aetiology of LS is still unknown, it is hypothesized to be an autoimmune disorder with a genetic component. 3 Currently, treatment of LS is mainly initiated to relieve symptoms of pruritis and pain, to reduce the progression of the skin alterations and eventually decrease the risk of cancer. Conventional treatment of LS consists of local application of corticosteroids, for example clobetasol propionate. 5 In severe cases of therapy-resistant LS, immunosuppressive agents (e.g. calcineurin inhibitors) can be administered, which inhibit T-cell activation. [6][7][8] However, clinical evidence

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“…[95] The gelation speed of natural polysaccharide materials, such as alginate (alg), hyaluronic acid (HA), chitosan (CS), dextran (Dex), and cellulose, is fast. [96][97][98][99][100][101] CS with high adsorption capacity, biocompatibility, and biodegradation, is a commonly used polysaccharide biopolymer derived from chitin. [102] The interface characteristics of MPRs prepared from CS are detailed as follows.…”

Section: Mprs Prepared By Physical Conversion Of Materials and Their ...mentioning

confidence: 99%

Microfluidic Particle Reactors: From Interface Characteristics to Cells and Drugs Related Biomedical Applications

Xin

et al. 2022

Adv Materials Inter

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with advanced functions, [6] can be attributed to two aspects. 1) The exquisite control and manipulation abilities of fluids at a microscale have reached a new height as droplet microfluidic technology is leaping forward. The precisely tunable interface characteristics of emulsion templates, determined by the optimization of fluids composition and interfacial complexity, contribute to the inherent interface properties of MPRs. [7][8][9][10] 2) The introduction of advanced materials expands the interface characteristics of the MPRs. Considerable natural polymers, synthetic polymers, and stimuli-responsive biomaterials have been employed continuously with the development of materials science. As a result, a series of performances possessed by the materials can significantly improve the inherent interface characteristics of the MPRs under a combination of the mentioned advanced materials. [11][12][13][14][15][16] Overall, researchers have stressed the improvement of the development process of interface characteristics and functions (such as substance encapsulation and controlled release) by providing novel technical innovations in every aspect to support biomedical clinical applications related to cells and drugs. Recently, the types, preparation methods, and biomedical applications of MPRs have been systematically presented in several excellent reviews. [3][4][5][8][9][10][17][18][19][20] The thermodynamic properties of liquid-liquid droplet reactors have been analyzed more specifically in some reviews. [7,17] However, the origin of interface characteristics of MPRs, as well as the function and cuttingedge cell-and drug-related biomedical applications determined by the interface characteristics, are deficient in a systematic summary. This review highlights that different emulsion templates endow the inherent interface characteristics of MPRs. Besides, the methods of converting emulsion templates into MPRs are summarized by introducing specific functional biomaterials, followed by the flexible and adjustable interface characteristics expanded by the mentioned materials. Moreover, the biomedical applications related to cells and drugs are analyzed based on the mentioned unique interface characteristics of the MPRs. Furthermore, the existing challenges regarding the current status are presented, and the subsequent development of the MPRs is illustrated from various perspectives (Scheme 1).

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Hyaluronic Acid Hydrogel Microspheres for Slow Release Stem Cell Delivery

Cited by 27 publications

References 51 publications

PEGDA microencapsulated allogeneic islets reverse canine diabetes without immunosuppression

PEGDA microencapsulated allogeneic islets reverse canine diabetes without immunosuppression

Autologous lipoaspirate as a new treatment of vulvar lichen sclerosus: A review on literature

Microfluidic Particle Reactors: From Interface Characteristics to Cells and Drugs Related Biomedical Applications

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