Abstract:Transplantation of microencapsulated islet cells holds great potential for the treatment of type 1 diabetes mellitus. However, its clinical translation is hampered by the peri‐transplantation loss of islet viability and functionality in the microcapsules. In this work, a novel islet cells biomimetic microencapsulant material that is based on the interpenetrating networks of alginate and extracellular matrix (ECM) hydrogel composite (AEC) is presented. The ECM component is derived from human lipoaspirate. In si… Show more
“…Wang et al show that MIN6 β-cells could exhibit larger proliferation rate and higher glucose sensitivity with insulin secretion when human adipose ECM was incorporated, suggesting the importance of cell–matrix interaction. 19 Hence, hydrogels are excellent platforms for artificial functional islet construction, which could dynamically and precisely control glucose balance in vivo and circumvent the drawbacks of long-term insulin injection.…”
Section: In Vitro and In Vivo Potential Applications Of Hydrogelmentioning
confidence: 99%
“…The interaction between cell and hydrogel is complex and dynamic, which exerts significant impacts on tissue physiological (e.g., cell spreading, 14 proliferation, 15 migration, 16 stemness, 17 differentiation, 18 etc.) and pathological processes, such as cell apoptosis, 19 fibrosis, 20 immunological rejection, 21 etc. Regarding this, a comprehensive and deep understanding of cell–hydrogel interaction especially at the molecular level is of great importance, which is helpful for guiding the rational design of hydrogels and facilitating their clinic translation in the future.…”
Hydrogel is a type of versatile platform with various biomedical applications after rational structure and functional design that leverages on material engineering to modulate its physicochemical properties (e.g., stiffness, pore size, viscoelasticity, microarchitecture, degradability, ligand presentation, stimulus-responsive properties, etc.) and influence cell signaling cascades and fate. In the past few decades, a plethora of pioneering studies have been implemented to explore the cell–hydrogel matrix interactions and figure out the underlying mechanisms, paving the way to the lab-to-clinic translation of hydrogel-based therapies. In this review, we first introduced the physicochemical properties of hydrogels and their fabrication approaches concisely. Subsequently, the comprehensive description and deep discussion were elucidated, wherein the influences of different hydrogels properties on cell behaviors and cellular signaling events were highlighted. These behaviors or events included integrin clustering, focal adhesion (FA) complex accumulation and activation, cytoskeleton rearrangement, protein cyto-nuclei shuttling and activation (e.g., Yes-associated protein (YAP), catenin, etc.), cellular compartment reorganization, gene expression, and further cell biology modulation (e.g., spreading, migration, proliferation, lineage commitment, etc.). Based on them, current in vitro and in vivo hydrogel applications that mainly covered diseases models, various cell delivery protocols for tissue regeneration and disease therapy, smart drug carrier, bioimaging, biosensor, and conductive wearable/implantable biodevices, etc. were further summarized and discussed. More significantly, the clinical translation potential and trials of hydrogels were presented, accompanied with which the remaining challenges and future perspectives in this field were emphasized. Collectively, the comprehensive and deep insights in this review will shed light on the design principles of new biomedical hydrogels to understand and modulate cellular processes, which are available for providing significant indications for future hydrogel design and serving for a broad range of biomedical applications.
“…Wang et al show that MIN6 β-cells could exhibit larger proliferation rate and higher glucose sensitivity with insulin secretion when human adipose ECM was incorporated, suggesting the importance of cell–matrix interaction. 19 Hence, hydrogels are excellent platforms for artificial functional islet construction, which could dynamically and precisely control glucose balance in vivo and circumvent the drawbacks of long-term insulin injection.…”
Section: In Vitro and In Vivo Potential Applications Of Hydrogelmentioning
confidence: 99%
“…The interaction between cell and hydrogel is complex and dynamic, which exerts significant impacts on tissue physiological (e.g., cell spreading, 14 proliferation, 15 migration, 16 stemness, 17 differentiation, 18 etc.) and pathological processes, such as cell apoptosis, 19 fibrosis, 20 immunological rejection, 21 etc. Regarding this, a comprehensive and deep understanding of cell–hydrogel interaction especially at the molecular level is of great importance, which is helpful for guiding the rational design of hydrogels and facilitating their clinic translation in the future.…”
Hydrogel is a type of versatile platform with various biomedical applications after rational structure and functional design that leverages on material engineering to modulate its physicochemical properties (e.g., stiffness, pore size, viscoelasticity, microarchitecture, degradability, ligand presentation, stimulus-responsive properties, etc.) and influence cell signaling cascades and fate. In the past few decades, a plethora of pioneering studies have been implemented to explore the cell–hydrogel matrix interactions and figure out the underlying mechanisms, paving the way to the lab-to-clinic translation of hydrogel-based therapies. In this review, we first introduced the physicochemical properties of hydrogels and their fabrication approaches concisely. Subsequently, the comprehensive description and deep discussion were elucidated, wherein the influences of different hydrogels properties on cell behaviors and cellular signaling events were highlighted. These behaviors or events included integrin clustering, focal adhesion (FA) complex accumulation and activation, cytoskeleton rearrangement, protein cyto-nuclei shuttling and activation (e.g., Yes-associated protein (YAP), catenin, etc.), cellular compartment reorganization, gene expression, and further cell biology modulation (e.g., spreading, migration, proliferation, lineage commitment, etc.). Based on them, current in vitro and in vivo hydrogel applications that mainly covered diseases models, various cell delivery protocols for tissue regeneration and disease therapy, smart drug carrier, bioimaging, biosensor, and conductive wearable/implantable biodevices, etc. were further summarized and discussed. More significantly, the clinical translation potential and trials of hydrogels were presented, accompanied with which the remaining challenges and future perspectives in this field were emphasized. Collectively, the comprehensive and deep insights in this review will shed light on the design principles of new biomedical hydrogels to understand and modulate cellular processes, which are available for providing significant indications for future hydrogel design and serving for a broad range of biomedical applications.
“…In recent work, researchers have investigated strategies to improve the ability of this polymer to mimic a natural ECM matrix. In one such paper, researchers combined human adipose tissue-derived ECM hydrogel with ALG matrix to form hybrid interpenetrating network microparticles for encapsulation of islet cells [ 16 ]. Fig.…”
Section: Mechanics Of Microencapsulationmentioning
Mapping a new therapeutic route can be fraught with challenges, but recent developments in the preparation and properties of small particles combined with significant improvements to tried and tested techniques offer refined cell targeting with tremendous translational potential. Regenerating new cells through the use of compounds that regulate epigenetic pathways represents an attractive approach that is gaining increased attention for the treatment of several diseases including Type 1 Diabetes and cardiomyopathy. However, cells that have been regenerated using epigenetic agents will still encounter immunological barriers as well as limitations associated with their longevity and potency during transplantation. Strategies aimed at protecting these epigenetically regenerated cells from the host immune response include microencapsulation. Microencapsulation can provide new solutions for the treatment of many diseases. In particular, it offers an advantageous method of administering therapeutic materials and molecules that cannot be substituted by pharmacological substances. Promising clinical findings have shown the potential beneficial use of microencapsulation for islet transplantation as well as for cardiac, hepatic, and neuronal repair. For the treatment of diseases such as type I diabetes that requires insulin release regulated by the patient's metabolic needs, microencapsulation may be the most effective therapeutic strategy. However, new materials need to be developed, so that transplanted encapsulated cells are able to survive for longer periods in the host. In this article, we discuss microencapsulation strategies and chart recent progress in nanomedicine that offers new potential for this area in the future.
“…In another study reported by Wang et al, novel thermosensitive interpenetrating networks (IPN) of alginate and human adipose tissue-derived ECM were fabricated as a biomimetic encapsulate environment for islets delivery (J. K. Wang J. K. et al, 2020 ). For encapsulation, islets were added to an alginate solution, then the system was crosslinked through ionic gelation, and finally, the microencapsulated structure was added to the ECM-derived hydrogel ( Figure 1 ).…”
“… Schematic illustrating fabrication steps alginate microcapsules containing human adipose tissue-derived ECM and microencapsulation of pancreatic islets (J. K. Wang J. K. et al, 2020 ). …”
Islet transplantation provides a promising strategy in treating type 1 diabetes as an autoimmune disease, in which damaged β-cells are replaced with new islets in a minimally invasive procedure. Although islet transplantation avoids the complications associated with whole pancreas transplantations, its clinical applications maintain significant drawbacks, including long-term immunosuppression, a lack of compatible donors, and blood-mediated inflammatory responses. Biomaterial-assisted islet transplantation is an emerging technology that embeds desired cells into biomaterials, which are then directly transplanted into the patient, overcoming the aforementioned challenges. Among various biomaterials, hydrogels are the preferred biomaterial of choice in these transplants due to their ECM-like structure and tunable properties. This review aims to present a comprehensive overview of hydrogel-based biomaterials that are engineered for encapsulation of insulin-secreting cells, focusing on new hydrogel design and modification strategies to improve β-cell viability, decrease inflammatory responses, and enhance insulin secretion. We will discuss the current status of clinical studies using therapeutic bioengineering hydrogels in insulin release and prospective approaches.
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