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      Natural 3D-Printed Bioinks for Skin Regeneration and Wound Healing: A Systematic Review

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          Abstract

          Three-dimensional bioprinting has rapidly paralleled many biomedical applications and assisted in advancing the printing of complex human organs for a better therapeutic practice. The objective of this systematic review is to highlight evidence from the existing studies and evaluate the effectiveness of using natural-based bioinks in skin regeneration and wound healing. A comprehensive search of all relevant original articles was performed based on prespecified eligibility criteria. The search was carried out using PubMed, Web of Science, Scopus, Medline Ovid, and ScienceDirect. Eighteen articles fulfilled the inclusion and exclusion criteria. The animal studies included a total of 151 animals with wound defects. A variety of natural bioinks and skin living cells were implanted in vitro to give insight into the technique through different assessments and findings. Collagen and gelatin hydrogels were most commonly used as bioinks. The follow-up period ranged between one day and six weeks. The majority of animal studies reported that full wound closure was achieved after 2–4 weeks. The results of both in vitro cell culture and in vivo animal studies showed the positive impact of natural bioinks in promoting wound healing. Future research should be focused more on direct the bioprinting of skin wound treatments on animal models to open doors for human clinical trials.

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          Most cited references 31

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          Additive manufacturing of tissues and organs

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            Design and fabrication of human skin by three-dimensional bioprinting.

            Three-dimensional (3D) bioprinting, a flexible automated on-demand platform for the free-form fabrication of complex living architectures, is a novel approach for the design and engineering of human organs and tissues. Here, we demonstrate the potential of 3D bioprinting for tissue engineering using human skin as a prototypical example. Keratinocytes and fibroblasts were used as constituent cells to represent the epidermis and dermis, and collagen was used to represent the dermal matrix of the skin. Preliminary studies were conducted to optimize printing parameters for maximum cell viability as well as for the optimization of cell densities in the epidermis and dermis to mimic physiologically relevant attributes of human skin. Printed 3D constructs were cultured in submerged media conditions followed by exposure of the epidermal layer to the air-liquid interface to promote maturation and stratification. Histology and immunofluorescence characterization demonstrated that 3D printed skin tissue was morphologically and biologically representative of in vivo human skin tissue. In comparison with traditional methods for skin engineering, 3D bioprinting offers several advantages in terms of shape- and form retention, flexibility, reproducibility, and high culture throughput. It has a broad range of applications in transdermal and topical formulation discovery, dermal toxicity studies, and in designing autologous grafts for wound healing. The proof-of-concept studies presented here can be further extended for enhancing the complexity of the skin model via the incorporation of secondary and adnexal structures or the inclusion of diseased cells to serve as a model for studying the pathophysiology of skin diseases.
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              Current Status of Bioinks for Micro-Extrusion-Based 3D Bioprinting

               Amit Panwar,  Lay Tan (2016)
              Recent developments in 3D printing technologies and design have been nothing short of spectacular. Parallel to this, development of bioinks has also emerged as an active research area with almost unlimited possibilities. Many bioinks have been developed for various cells types, but bioinks currently used for 3D printing still have challenges and limitations. Bioink development is significant due to two major objectives. The first objective is to provide growth- and function-supportive bioinks to the cells for their proper organization and eventual function and the second objective is to minimize the effect of printing on cell viability, without compromising the resolution shape and stability of the construct. Here, we will address the current status and challenges of bioinks for 3D printing of tissue constructs for in vitro and in vivo applications.
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                Author and article information

                Journal
                Polymers (Basel)
                Polymers (Basel)
                polymers
                Polymers
                MDPI
                2073-4360
                10 August 2020
                August 2020
                : 12
                : 8
                Affiliations
                [1 ]Centre for Tissue Engineering Centre and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; alialadil777@ 123456gmail.com (A.S.); angela@ 123456ppukm.ukm.edu.my (N.M.H.)
                [2 ]Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; m.abid.nordin@ 123456gmail.com
                [3 ]Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; gabrielchinky@ 123456gmail.com
                [4 ]3D Gens Sdn Bhd, 18, Jalan Kerawang U8/108, Bukit Jelutong, Shah Alam 40150, Selangor, Malaysia; izhar@ 1234563dgens.com
                Author notes
                [* ]Correspondence: fauzibusra@ 123456ukm.edu.my ; Tel.: +60-196-551-020
                Article
                polymers-12-01782
                10.3390/polym12081782
                7463743
                32784960
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

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