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      Hydrogel Scaffolds to Deliver Cell Therapies for Wound Healing

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          Abstract

          Cutaneous wounds are a growing global health burden as a result of an aging population coupled with increasing incidence of diabetes, obesity, and cancer. Cell-based approaches have been used to treat wounds due to their secretory, immunomodulatory, and regenerative effects, and recent studies have highlighted that delivery of stem cells may provide the most benefits. Delivering these cells to wounds with direct injection has been associated with low viability, transient retention, and overall poor efficacy. The use of bioactive scaffolds provides a promising method to improve cell therapy delivery. Specifically, hydrogels provide a physiologic microenvironment for transplanted cells, including mechanical support and protection from native immune cells, and cell–hydrogel interactions may be tailored based on specific tissue properties. In this review, we describe the current and future directions of various cell therapies and usage of hydrogels to deliver these cells for wound healing applications.

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          Most cited references129

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          Alginate: properties and biomedical applications.

          Alginate is a biomaterial that has found numerous applications in biomedical science and engineering due to its favorable properties, including biocompatibility and ease of gelation. Alginate hydrogels have been particularly attractive in wound healing, drug delivery, and tissue engineering applications to date, as these gels retain structural similarity to the extracellular matrices in tissues and can be manipulated to play several critical roles. This review will provide a comprehensive overview of general properties of alginate and its hydrogels, their biomedical applications, and suggest new perspectives for future studies with these polymers.
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            Designing hydrogels for controlled drug delivery

            Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.
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              Wound repair and regeneration.

              The repair of wounds is one of the most complex biological processes that occur during human life. After an injury, multiple biological pathways immediately become activated and are synchronized to respond. In human adults, the wound repair process commonly leads to a non-functioning mass of fibrotic tissue known as a scar. By contrast, early in gestation, injured fetal tissues can be completely recreated, without fibrosis, in a process resembling regeneration. Some organisms, however, retain the ability to regenerate tissue throughout adult life. Knowledge gained from studying such organisms might help to unlock latent regenerative pathways in humans, which would change medical practice as much as the introduction of antibiotics did in the twentieth century.
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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                03 May 2021
                2021
                : 9
                : 660145
                Affiliations
                Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine , Stanford, CA, United States
                Author notes

                Edited by: Liyuan Zhang, Harvard University, United States

                Reviewed by: Rajendra Kumar Singh, Institute of Tissue Regeneration Engineering (ITREN), South Korea; Daniel Alge, Texas A&M University, United States

                *Correspondence: Geoffrey C. Gurtner, ggurtner@ 123456stanford.edu

                These authors have contributed equally to this work and share co-first authorship

                This article was submitted to Biomaterials, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                10.3389/fbioe.2021.660145
                8126987
                34012956
                47814bd7-5348-4679-b53a-e70ad3085d00
                Copyright © 2021 Sivaraj, Chen, Chattopadhyay, Henn, Wu, Noishiki, Magbual, Mittal, Mermin-Bunnell, Bonham, Trotsyuk, Barrera, Padmanabhan, Januszyk and Gurtner.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 January 2021
                : 07 April 2021
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 129, Pages: 17, Words: 0
                Categories
                Bioengineering and Biotechnology
                Review

                hydrogel,cell therapy,wound healing,fibrosis,stem cell
                hydrogel, cell therapy, wound healing, fibrosis, stem cell

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