Partially Oxidized Alginate as a Biodegradable Carrier for Glucose‐Responsive Insulin Delivery and Islet Cell Replacement Therapy

Volpatti, Lisa R.; Bochenek, Matthew A.; Facklam, Amanda; Burns, Delaney M.; MacIsaac, Corina; Morgart, Alexander; Walters, Benjamin; Langer, Robert; Anderson, Daniel G.

doi:10.1002/adhm.202201822

Cited by 12 publications

(3 citation statements)

References 50 publications

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“…ADA in its injectable form has been used in combination with different natural (chitosan, gelatin, carboxyl methyl chitosan, etc.) and synthetic polymers (Polyethylene glycol) for various applications like cardiac tissue engineering, [16] drug delivery, [17] wound dressing, [18] meniscal tear repair, [15] adipose tissue engineering, [19] cartilage regeneration, [20] dental enamel regeneration, [21] intervertebral disc cell therapy, [22] nerve tissue engineering, [23] islet cell transplantation, [24] etc.…”

Section: Introductionmentioning

confidence: 99%

Implications of Storage Conditions on the Characteristics of Alginate Dialdehyde and Its Hydrogels

Resmi,

Parvathy,

Anjali

et al. 2024

ChemistrySelect

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A review of recent literature reveals a spurt in the publications using alginate dialdehyde (ADA)‐based hydrogels. This study evaluates the stability and characteristics of ADA solutions stored at different temperatures (4 & −20 °C; designated as ADA4°C & ADA−20°C) and durations (1, 3, and 6 months), and gives valuable insights into the shelf life, a parameter important in a clinical setting. ADA solutions were characterized for their viscosity, aldehyde content, molecular weight, and chemical structure before and after storage. The solution viscosities of ADA4°C showed a decreasing trend over 6 months while that of ADA‐20°C showed an increase. Compared to freshly prepared ADA, a significant reduction in aldehyde content, from 40.1±1.4 % to 37.1±1.01 %, was observed for ADA4°C stored for 6 months, but the aldehyde content was stable for ADA−20°C stored for the same period. Molecular weight remained stable (~6800 g/mol) irrespective of the storage temperatures. Injectable hydrogels were prepared by reacting the stored ADA solutions with 20 % aqueous solutions of gelatin. Hydrogels prepared with ADA stored at 4 °C for 6 months showed a significant increase in gelation time from 4.3±1.5 to 8.79±0.1 min and a decrease in degree of crosslinking from 54.3±1.4 % to 29.2±2.3 %. A decreasing trend was observed for properties such as water uptake (from 470 to 961 %) and tensile strength (from 348 to 282 kPa). Hydrogels made with ADA−20°C demonstrated better retention of physicochemical properties over time. In vitro studies revealed that the hydrogels showed a non‐cytotoxic response towards L929 cells irrespective of the storage conditions. LIVE/DEAD assay and F‐Actin staining revealed good cell proliferation on the hydrogels. In conclusion, retention of the properties of ADA in its aqueous solution requires careful control of storage temperatures.

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Section: Introductionmentioning

confidence: 99%

Implications of Storage Conditions on the Characteristics of Alginate Dialdehyde and Its Hydrogels

Resmi,

Parvathy,

Anjali

et al. 2024

ChemistrySelect

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“…Stimuli-responsive systems represent an efficient strategy to tackle this issue and promote a better glycemic control. In hydrogel-based devices, the variety of stimuli that trigger insulin release include physiological temperature, , pH, − electrical current, − dynamic covalent bonding, or glucose itself, ,− among others …”

Section: Introductionmentioning

confidence: 99%

“…To achieve the desired concentration of insulin release, which is a challenging task, several polymeric matrices have been proven to be biocompatible and biodegradable, such as chitosan or alginate. , Most importantly, however, insulin release requires a smarter and more controlled delivery, which is expected to take into account the patient’s glucose level in blood. Stimuli-responsive systems represent an efficient strategy to tackle this issue and promote a better glycemic control.…”

Section: Introductionmentioning

confidence: 99%

Electroresponsive Thiol–Yne Click-Hydrogels for Insulin Smart Delivery: Tackling Sustained Release and Leakage Control

Muñoz-Galán,

Enshaei,

Silva

et al. 2024

ACS Appl. Polym. Mater.

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Diabetes is a metabolic disorder caused by the body's inability to produce or use insulin. Considering the figures projected by the World Health Organization, research on insulin therapy is crucial. Hence, we present a soft biointerface based on a thiol−yne poly(ethylene glycol) (PEG) click-hydrogel as an advanced treatment option to administrate insulin. Most importantly, the device is rendered electroactive by incorporating biocompatible poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs) as conductive moieties to precisely control the release of insulin over an extended period through electrochemical stimulation (ES). The device has been carefully optimized on account of: (i) the main interactions established between PEDOT-and PEG-based moieties, which have been studied by density functional theory calculations, and reveal the choice of 4-arm PEG precursors as most suitable cross-linkers; and (ii) the concentration of PEDOT NPs in the device, which has been determined considering minimal interference with the gelation process, as well as the resulting morphological, mechanical, electrochemical, and cytocompatible properties of the PEG-based click-hydrogels. Finally, the management over insulin delivery through ES is verified in vitro, with released insulin being detected by highperformance liquid chromatography. Overall, our hydrogel-based device establishes a method for controlled insulin delivery with the potential for translation to other relevant bioelectronic applications.

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A Biomineralized Bifunctional Patient‐Friendly Nanosystem for Sustained Glucose Monitoring and Control in Diabetes

Yang,

Chan,

Chan

et al. 2024

Small Methods

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Regular blood glucose monitoring and control is necessary for people with type 1 or advanced type 2 diabetes, yet diagnosing and treating patients with diabetes in an accurate, sustained and patient‐friendly manner remains limited. Here, a glucose‐responsive bifunctional nanosystem (PGOxMns) is constructed via one‐pot biomineralisation of manganese dioxide with glucose oxidase and ε‐poly‐L‐lysine. Under hyperglycaemic conditions, the cascade reactions that occur when glucose interacts with PGOxMns can trigger the production of Mn(II), which enhances the magnetic resonance imaging signal. Simultaneously, manganese dioxide catalyses the decomposition of toxic hydrogen peroxide into oxygen, which also maintains glucose oxidase (GOx) activity. In an in vivo model of diabetes, PGOxMns is used to monitor glucose levels (0–20 mm) and allowed identification of diabetic mice via T1‐weighted MRI. Furthermore, PGOxMns is found to have a high insulin‐loading capacity (83.6%), likely due to its positive charge. A single subcutaneous injection of insulin‐loaded nanosystem (Ins‐PGOxMns) into diabetic mice resulted in a rapid and efficient response to a glucose challenge and prolonged blood glucose level control (< 200 mg dL−1) for up to 50 h. Overall, this proof‐of‐concept study demonstrates the feasibility of using biomineralised nanosystems to develop patient‐friendly strategies for glucose monitoring and control.

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Partially Oxidized Alginate as a Biodegradable Carrier for Glucose‐Responsive Insulin Delivery and Islet Cell Replacement Therapy

Cited by 12 publications

References 50 publications

Implications of Storage Conditions on the Characteristics of Alginate Dialdehyde and Its Hydrogels

Implications of Storage Conditions on the Characteristics of Alginate Dialdehyde and Its Hydrogels

Electroresponsive Thiol–Yne Click-Hydrogels for Insulin Smart Delivery: Tackling Sustained Release and Leakage Control

A Biomineralized Bifunctional Patient‐Friendly Nanosystem for Sustained Glucose Monitoring and Control in Diabetes

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