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      Advances in spray products for skin regeneration

      review-article
      a , b , c , d , e , f , g , b , c , d , e , h , a , b , c , d , e , ∗∗ , a , c , d , e , i ,
      Bioactive Materials
      KeAi Publishing
      Skin, Spray, Tissue engineering, Fibrin, Hydrogel, ATMP, advanced therapy medicinal product, BLA, Biologic License Application, CAT, Committee for Advances Therapies, CEA, cultured epithelial autograft, CFR, Code of Federal Regulations, CHMP, Committee for Medicinal Product for Human Use, CTD, Common Technical Document, DMEM, Dulbecco's Modified Eagle's medium, ECM, extracellular matrix, EMA, European Medicines Agency, EU, European Union, FDA, Food and Drug Administration, GAGs, glycosaminoglycans, GLP, Good Laboratory Practice, GMP, Good Manufacturing Practice, HA, hyaluronic acid, HCT/Ps, human cells, tissues, and cellular and tissue-based products, ISO, International Organization for Standardization, MA, marketing authorization, NP, Notified body, OTAT, Office of Tissues and Advanced Therapies, PCL, polycaprolactone, PEG, polyethylene glycol, PHSA, Public Health Service Act, PMA, Premarket Approval, PRF, platelet rich fibrin, PRP, platelet rich plasma, PU, polyurethane, QMS, Quality Management System, TE, tissue engineering, USA, United States of America

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          Abstract

          To date, skin wounds are still an issue for healthcare professionals. Although numerous approaches have been developed over the years for skin regeneration, recent advances in regenerative medicine offer very promising strategies for the fabrication of artificial skin substitutes, including 3D bioprinting, electrospinning or spraying, among others. In particular, skin sprays are an innovative technique still under clinical evaluation that show great potential for the delivery of cells and hydrogels to treat acute and chronic wounds. Skin sprays present significant advantages compared to conventional treatments for wound healing, such as the facility of application, the possibility to treat large wound areas, or the homogeneous distribution of the sprayed material. In this article, we review the latest advances in this technology, giving a detailed description of investigational and currently commercially available acellular and cellular skin spray products, used for a variety of diseases and applying different experimental materials. Moreover, as skin sprays products are subjected to different classifications, we also explain the regulatory pathways for their commercialization and include the main clinical trials for different skin diseases and their treatment conditions. Finally, we argue and suggest possible future trends for the biotechnology of skin sprays for a better use in clinical dermatology.

          Graphical abstract

          Highlights

          • Skin sprays represent a promising technique for wound healing applications.

          • Skin sprays can deliver cells and hydrogels with great facility over large wounds.

          • Many skin spray products have been studied, only a few have been commercialized.

          • Numerous clinical trials study spray products for skin diseases like psoriasis.

          • Improved spraying devices should be developed for different materials and cells.

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          Most cited references159

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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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            Electrospinning: a fascinating fiber fabrication technique.

            With the emergence of nanotechnology, researchers become more interested in studying the unique properties of nanoscale materials. Electrospinning, an electrostatic fiber fabrication technique has evinced more interest and attention in recent years due to its versatility and potential for applications in diverse fields. The notable applications include in tissue engineering, biosensors, filtration, wound dressings, drug delivery, and enzyme immobilization. The nanoscale fibers are generated by the application of strong electric field on polymer solution or melt. The non-wovens nanofibrous mats produced by this technique mimics extracellular matrix components much closely as compared to the conventional techniques. The sub-micron range spun fibers produced by this process, offer various advantages like high surface area to volume ratio, tunable porosity and the ability to manipulate nanofiber composition in order to get desired properties and function. Over the years, more than 200 polymers have been electrospun for various applications and the number is still increasing gradually with time. With these in perspectives, we aim to present in this review, an overview of the electrospinning technique with its promising advantages and potential applications. We have discussed the electrospinning theory, spinnable polymers, parameters (solution and processing), which significantly affect the fiber morphology, solvent properties and melt electrospinning (alternative to solution electrospinning). Finally, we have focused on varied applications of electrospun fibers in different fields and concluded with the future prospects of this efficient technology. (c) 2010 Elsevier Inc. All rights reserved.
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              Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering.

              L. Ma (2003)
              Porous scaffolds for skin tissue engineering were fabricated by freeze-drying the mixture of collagen and chitosan solutions. Glutaraldehyde (GA) was used to treat the scaffolds to improve their biostability. Confocal laser scanning microscopy observation confirmed the even distribution of these two constituent materials in the scaffold. The GA concentrations have a slight effect on the cross-section morphology and the swelling ratios of the cross-linked scaffolds. The collagenase digestion test proved that the presence of chitosan can obviously improve the biostability of the collagen/chitosan scaffold under the GA treatment, where chitosan might function as a cross-linking bridge. A detail investigation found that a steady increase of the biostability of the collagen/chitosan scaffold was achieved when GA concentration was lower than 0.1%, then was less influenced at a still higher GA concentration up to 0.25%. In vitro culture of human dermal fibroblasts proved that the GA-treated scaffold could retain the original good cytocompatibility of collagen to effectively accelerate cell infiltration and proliferation. In vivo animal tests further revealed that the scaffold could sufficiently support and accelerate the fibroblasts infiltration from the surrounding tissue. Immunohistochemistry analysis of the scaffold embedded for 28 days indicated that the biodegradation of the 0.25% GA-treated scaffold is a long-term process. All these results suggest that collagen/chitosan scaffold cross-linked by GA is a potential candidate for dermal equivalent with enhanced biostability and good biocompatibility.
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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                08 March 2022
                October 2022
                08 March 2022
                : 16
                : 187-203
                Affiliations
                [a ]Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain
                [b ]Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
                [c ]BioFab i3D Lab - Biofabrication and 3D (bio)printing Laboratory, Granada, Spain
                [d ]Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain
                [e ]Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospitals of Granada ‐ University of Granada, Granada, Spain
                [f ]R&D Human Health, Bioibérica S.A.U, Barcelona, Spain
                [g ]Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain
                [h ]Complex Tissue Regeneration Department, MERLN Institute for Technology Inspired Regenerative Medicine, Universiteitssingel 40, 6229ER Maastricht, the Netherlands
                [i ]Department of Health Sciences, University of Jaén, Jaén, Spain
                Author notes
                []Corresponding author. Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain. elruiz@ 123456ujaen.es
                [∗∗ ]Corresponding author. Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain. jmarchal@ 123456go.ugr.es
                Article
                S2452-199X(22)00097-4
                10.1016/j.bioactmat.2022.02.023
                8965724
                35386328
                66b817d3-71e8-4610-b87e-62d66e6e7904
                © 2022 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 29 October 2021
                : 22 January 2022
                : 18 February 2022
                Categories
                Review Article

                skin,spray,tissue engineering,fibrin,hydrogel,atmp, advanced therapy medicinal product,bla, biologic license application,cat, committee for advances therapies,cea, cultured epithelial autograft,cfr, code of federal regulations,chmp, committee for medicinal product for human use,ctd, common technical document,dmem, dulbecco's modified eagle's medium,ecm, extracellular matrix,ema, european medicines agency,eu, european union,fda, food and drug administration,gags, glycosaminoglycans,glp, good laboratory practice,gmp, good manufacturing practice,ha, hyaluronic acid,hct/ps, human cells, tissues, and cellular and tissue-based products,iso, international organization for standardization,ma, marketing authorization,np, notified body,otat, office of tissues and advanced therapies,pcl, polycaprolactone,peg, polyethylene glycol,phsa, public health service act,pma, premarket approval,prf, platelet rich fibrin,prp, platelet rich plasma,pu, polyurethane,qms, quality management system,te, tissue engineering,usa, united states of america

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