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

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.

Collagen in Wound Healing

“…Three dimensional (3D) bioprinting is an evolving adaptive manufacturing technique that offers the development of wound treatments that can deal with the issues presented by traditional wound dressings (i.e., need for frequent dressing change, adherence to wound tissue making dressing changes painful) [ 126 ]. The bioprinting process integrates cell-laden hydrogels, also called bioinks, together with motorized systems to create complex structures that can be catered precisely to the patient or situation in question [ 79 , 80 , 126 , 127 , 128 ]. In 2009, a 3D-printed human skin construct incorporating collagen I together with fibroblasts and keratinocytes was the first successful attempt at creating a skin implant.…”

“…Collagen bioinks are currently the most popular material for 3D engineering, primarily because of the history of their use in clinical practice, biocompatibility and low immunogenicity. Collagen I is the most common type used for bioink manufacturing and has been used in the laboratory-based bioprinting of skin, bone and cartilage, cardiovascular tissues, liver, nerve regeneration and cornea with limited testing conducted in vitro and in vivo (small animal models) [ 79 , 80 , 126 ].…”

“…A key issue with collagen bioinks is the need for specific pH and temperatures to initiate matrix gelation that could be toxic to cells [ 130 ]. Additional challenges include precise tissue detailing (including development of structures like sweat glands and hair follicles) and the need for improved cross-linking techniques for structural control of the bioink-generated product [ 126 ]. The production of constructs for large wound areas is a challenge.…”

Cellulose Bio–ink on 3D Printing Applications

“…It helps in the study of cancer genesis, growth and response to cancer drugs. 45 3D structures imitate an entire tumor by coping with the cells with properties for the type of cancer and stage of the disease. In doing this, the 3D helps in cancer screening and Agaron based bio-inks From seaweeds, gel properties make it desired due to its mechanical strength and biocompatibility, supports epithelial and fibroblasts growth.…”

Shape Fidelity of 3D-Bioprinted Biodegradable Patches

“…3D bioprinting technologies offer rapid and early wound treatment to avoid aggravation, tissue damages, and hypertrophic scarring for multiple types of wounds, including burn, diabetic, surgical wounds. The 3D bioprinting technologies had been started to use for wound healing and skin regeneration in 2012 using natural bioink collagen, and it reached around 70 published studies by 2020 [ 18 ]. Extrusion-based bioprinting is the widely used method [ 19 ], and various crosslinking methods have been used, such as chemical crosslinking by calcium chloride [ 20 ] and UV light [ 21 , 22 ].…”