Functionalization of Alginate with Extracellular Matrix Peptides Enhances Viability and Function of Encapsulated Porcine Islets

Medina, Juan D.; Alexander, Michael P.; Hunckler, Michael D.; Fernández‐Yagüe, Marc A.; Coronel, María M.; Smink, Alexandra M.; Lakey, Jonathan R. T.; Vos, Paul de; Garcı́a, Andrés J.

doi:10.1002/adhm.202000102

Cited by 19 publications

(14 citation statements)

References 43 publications

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“…[ 32 ] A proposed method of obtaining such defined release profiles are through programmed delivery techniques, whereby chemically sensitive bonding is used to retain therapeutics on the gel, releasing once stimulated by a biological cue. [ 33 ] Although functionalization of polysaccharide‐based materials is achievable, [ 34–36 ] chemical alteration is typically undertaken prior to gelation, accompanied by complicated synthesis and at risk to affecting gelation properties thereafter. [ 37 ] As such, the often‐complex chemical structures (in terms of both chemical moieties and disparity in repeating saccharide units) of the polysaccharides currently used to formulate fluid gels, do not lend themselves to easily facilitate chemical tethers between microgel particle and biologically active molecules.…”

Section: Introductionmentioning

confidence: 99%

Tailoring Therapeutic Responses via Engineering Microenvironments with a Novel Synthetic Fluid Gel

Foster

Allen

Haj

et al. 2021

Adv Healthcare Materials

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This study reports the first fully synthetic fluid gel (SyMGels) using a simple poly(ethylene glycol) polymer. Fluid gels are an interesting class of materials: structured during gelation via shear‐confinement to form microparticulate suspensions, through a bottom‐up approach. Structuring in this way, when compared to first forming a gel and subsequently breaking it down, results in the formation of a particulate dispersion with particles “grown” in the shear flow. Resultantly, systems form a complex microstructure, where gelled particles concentrate remaining non‐gelled polymer within the continuous phase, creating an amorphous‐like interstitial phase. As such, these materials demonstrate mechanical characteristics typical of colloidal glasses, presenting solid‐like behaviors at rest with defined yielding; likely through intrinsic particle‐particle and particle‐polymer interactions. To date, fluid gels have been fabricated using polysaccharides with relatively complex chemistries, making further modifications challenging. SyMGels are easily functionalised, using simple click‐chemistry. This chemical flexibility, allows the creation of microenvironments with discrete biological decoration. Cellular control is demonstrated using MSC (mesenchymal stem cells)/chondrocytes and enables the regulation of key biomarkers such as aggrecan and SOX9. These potential therapeutic platforms demonstrate an important advancement in the biomaterial field, underpinning the mechanisms which drive their mechanical properties, and providing a versatile delivery system for advanced therapeutics.

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Section: Introductionmentioning

confidence: 99%

Tailoring Therapeutic Responses via Engineering Microenvironments with a Novel Synthetic Fluid Gel

Foster

Allen

Haj

et al. 2021

Adv Healthcare Materials

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show abstract

“…To provide a complete extracellular milieu with structural 3D support to the growing engineered tissue, the space around the perfused vessels was filled with hydrogel. In the experiments presented here, the hydrogel component consisted of the commonly used proteinaceous matrix Matrigel, however the platform can also readily accommodate without any additional modifications the use of other naturally derived matrices such as collagen, as well as synthetic artificial extracellular matrices such as poly(ethylene) glycol PEG 67 or alginate 68 . This technology provides a reliable fluidic coupling between the microfluidic grid and the host perfusion device, such that a continuous peristaltic pump driven perfusion is possible.…”

Section: Discussionmentioning

confidence: 99%

Engineering large-scale perfused tissues via synthetic 3D soft microfluidics

Grebenyuk

Fattah

Rustandi

et al. 2021

Preprint

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The vascularization of engineered tissues and organoids has remained a major unresolved challenge in regenerative medicine. While multiple approaches have been developed to vascularize in vitro tissues, it has thus far not been possible to generate sufficiently dense networks of small-scale vessels to perfuse large de novo tissues. Here, we achieve the perfusion of multi-mm3 tissue constructs by generating networks of synthetic capillary-scale 3D vessels. Our 3D soft microfluidic strategy is uniquely enabled by a 3D-printable 2-photon-polymerizable hydrogel formulation, which allows for precise microvessel printing at scales below the diffusion limit of living tissues. We demonstrate that these large-scale engineered tissues are viable, proliferative and exhibit complex morphogenesis during long-term in-vitro culture, while avoiding hypoxia and necrosis. We show by scRNAseq and immunohistochemistry that neural differentiation is significantly accelerated in perfused neural constructs. Additionally, we illustrate the versatility of this platform by demonstrating long-term perfusion of developing liver tissue. This fully synthetic vascularization platform opens the door to the generation of human tissue models at unprecedented scale and complexity.

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“…Other studies have also incorporated specific ECM peptides or combinations, 46,47 with similar reports of improved islet function. However, while some combinations of ECM peptides may improve islet function and viability, other combinations decrease insulin production in beta cells.…”

Section: Reengineering Of the Encapsulation Matrix To Mimic The Microenvironment Of The Nativementioning

confidence: 99%

“…Increased glucose-stimulated release of insulin and islet viability was observed in porcine islets encapsulated in RGD-bound alginate when compared to islets encapsulated in alginate non adhered to RGD and alginate adhered with other peptide sequences LRE, YIGSR, PDGEA, and PDSGR. 46 Enck et al . 45 modified alginate hydrogel microcapsule matrix by addition of decellularized ECM (dECM) components from human pancreas and observed improved stability of the morphology and mechanical strength of alginate microcapsules with significant increase in matrix stiffness of Sr 2+ relative to Ca 2+ crosslinked hydrogels (Figure 2), as well as improved function of encapsulated human islets (Figure 3).…”

Section: Reengineering Of the Encapsulation Matrix To Mimic The Microenvironment Of The Nativementioning

confidence: 99%

Islet cell encapsulation – Application in diabetes treatment

Opara¹,

Jost

Dagogo-Jack

et al. 2021

Exp Biol Med (Maywood)

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In this minireview, we briefly outline the hallmarks of diabetes, the distinction between type 1 and type 2 diabetes, the global incidence of diabetes, and its associated comorbidities. The main goal of the review is to highlight the great potential of encapsulated pancreatic islet transplantation to provide a cure for type 1 diabetes. Following a short overview of the different approaches to islet encapsulation, we provide a summary of the merits and demerits of each approach of the encapsulation technology. We then discuss various attempts to clinical translation with each model of encapsulation as well as the factors that have mitigated the full clinical realization of the promise of the encapsulation technology, the progress that has been made and the challenges that remain to be overcome. In particular, we pay significant attention to the emerging strategies to overcome these challenges. We believe that these strategies to enhance the performance of the encapsulated islet constructs discussed herein provide good platforms for additional work to achieve successful clinical translation of the encapsulated islet technology.

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Functionalization of Alginate with Extracellular Matrix Peptides Enhances Viability and Function of Encapsulated Porcine Islets

Abstract: Translation of transplanted alginate-encapsulated pancreatic islets to treat type 1 diabetes has been hindered by inconsistent long-term efficacy. This loss of graft function can be partially attributed

Cited by 19 publications

References 43 publications

Tailoring Therapeutic Responses via Engineering Microenvironments with a Novel Synthetic Fluid Gel

Tailoring Therapeutic Responses via Engineering Microenvironments with a Novel Synthetic Fluid Gel

Engineering large-scale perfused tissues via synthetic 3D soft microfluidics

Islet cell encapsulation – Application in diabetes treatment

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