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![Figure 1. Graphical abstract for wound healing phases [12]. Used under...](publication/357654081/figure/fig1/AS:1112560136912896@1642266415136/Graphical-abstract-for-wound-healing-phases-12-Used-under-the-Creative-Commons-License_Q320.jpg)
Skin substitutes can provide a temporary or permanent treatment option for chronic wounds. The selection of skin substitutes depends on several factors, including the type of wound and its severity. Full-thickness skin grafts (SGs) require a well-vascularised bed and sometimes will lead to contraction and scarring formation. Besides, donor sites fo...
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Citations
... When designing bioinks, the selection and source of living cells become crucial considerations since they directly influence the immune response following the implantation of printed scaffolds [141]. Primary skin cells like fibroblasts, keratinocytes, and melanocytes are often preferred for co-culturing during the creation of skin bioprinting constructs [142]. The printed tissue/organ must consistently support normal cellular activities, including cell migration capacity and proliferation rate [42]. ...
Objective:
This study endeavors to investigate the progression, research focal points, and budding trends in the realm of skin bioprinting over the past decade from a structural and temporal dynamics standpoint.
Methods:
Scholarly articles on skin bioprinting were obtained from WoSCC. A series of bibliometric tools comprising R software, CiteSpace, HistCite, and an alluvial generator were employed to discern historical characteristics, evolution of active topics, and upcoming tendencies in the area of skin bioprinting.
Findings:
Over the past decade, there has been a consistent rise in research interest in skin bioprinting, accompanied by an extensive array of meaningful scientific collaborations. Concurrently, diverse dynamic topics have emerged during various periods, as substantiated by an aggregate of 22 disciplines, 74 keywords, and 187 references demonstrating citation bursts. Four burgeoning research subfields were discerned through keyword clustering - namely, #3 "in situ bioprinting", #6 "vascular", #7 "xanthan gum", and #8 "collagen hydrogels". The keyword alluvial map reveals that Module 1, including "transplantation" etc., has primarily dominated the research module over the previous decade, maintaining enduring relevance despite annual shifts in keyword focus. Additionally, we mapped out the top six key modules from 2023 being "silk fibroin nanofiber", "system", "ionic liquid", "mechanism", and "foot ulcer". Three recent research subdivisions were identified via timeline visualization of references, particularly Clusters #0 "wound healing", #4 "situ mineralization", and #5 "3D bioprinter".
Conclusion:
Insights derived from bibliometric analyses illustrate present conditions and trends in skin bioprinting research, potentially aiding researchers in pinpointing central themes and pioneering novel investigative approaches in this field.
... 28,32,33 Conversely, low-viscosity hydrogel might result in inadequate biomimetic scaffold structures and poor shape fidelity. 34,35 The challenge of achieving both precise structural control and high cell viability simultaneously is a critical issue that needs to be addressed. ...
Skin lesions not only disrupt appearance and barrier functionality but also lead to severe microbial infections and immune-inflammatory responses, seriously affect physical and mental health. In situ printing involves the direct deposition of bio-ink to create or repair damaged tissues or organs within a clinical setting. In this study, we designed and fabricated a novel portable in situ printer. This handheld instrument exhibits excellent printing performance, allowing hydrogels to be patterned and molded on surfaces according to specific requirements. By utilizing a dual-component hydrogels co-printing approach with high and low viscosities, we achieved in situ cell-laden printing using low-viscosity hydrogel. This demonstrates the advantages of the device in maintaining cell viability and achieving hydrogel structuring. This approach opens up the possibilities for the efficient encapsulation of active components such as drugs, proteins, and cells, enabling controlled macro- and micro-structuring of hydrogels. This breakthrough finding highlights the potential of our technical approach in dermatological treatment and wound repair, by dynamically adapting and regulating microenvironments in conjunction with hydrogel scaffolds and cell reparative impetus.
... There are various clinical management methods for promoting wound healing [10,15] . Skin transplantation is an option, but the insufficient supply of autologous split skin transplantation materials is a global challenge [13,16] . Skin equivalents can also be used to promote wound healing [16][17] . ...
... Although skin transplantation is still the gold standard for the treatment of chronic wounds [13] , bioprinted scaffolds still have unique advantages compared to other skin engineering materials in the treatment of chronic wound healing [88] . In particular, they can promote healing by addressing the angiogenic disorders and inflammation that occur after the healing of chronic wounds, such as DFUs [88] . ...
... The self-healing ability of these organizational interfaces is usually limited [106] . Transplantation of autologous, allogeneic, or synthetic grafts is currently being used to treat tissue interfaces with limited effectiveness [13,15] , mainly due to the inability to form multilayer structures similar to tissue interfaces in a short period of time [106] . Computer-assisted bioprinting technology makes it possible for various biomaterials to be accurately arranged layer by layer in space [102][103] . ...
Most conventional therapies have limitations in the repair of complex wounds caused by chronic inflammation in patients with diabetic foot ulcers (DFUs). In response to the demand for more biotechnology strategies, bioprinting has been explored in the regeneration field in recent years. However, challenges remain regarding the structure of complex models and the selection of proper biomaterials. The purpose of this review is to introduce the current applications of bioprinting technology in chronic diabetic foot wound healing. First, the most common application of bioprinting in producing skin equivalents to promote wound healing is introduced; second, functional improvements in the treatment of chronic and difficult-to-heal DFU wounds facilitated by bioprinting applications are discussed; and last but not least, bioprinting applications in addressing unique diabetic foot disease characteristics are summarized. Furthermore, the present work summarizes material selection and correlations between three-dimensional (3D) bioprinting and a variety of biomimetic strategies for accelerating wound healing. Novel, biotechnological tools such as organoids for developing new biomaterials for bioprinting in the future are also discussed.
... Moreover, 3D-printed skin equivalents should (1) transport nutrients and drain wound exudates; (2) have porosity and mechanical properties that are as close to those of natural skin as possible; and (3) mimic the multilayered and multifunctional characteristics of natural skin [8,139]. Most of the relevant research has initially focused on single-structure skin mimicry [140][141][142]. For example, the dermis has been simulated by nanofibrillated cellulose (NFC), ALG, CMC, and encapsulated human-derived skin fibroblasts [141]. ...
The skin is the body's first line of defence, and its physiology is complex. When injury occurs, the skin goes through a complex recovery process, and there is the risk of developing a chronic wound. Therefore, proper wound care is critical during the healing process. In response to clinical needs, wound dressings have been developed. There are several types of wound dressings available for wound healing, but there are still many issues to overcome. With its high controllability and resolution, 3D printing technology is widely regarded as the technology of the next global industrial and manufacturing revolution, and it is a key driving force in the development of wound dressings. Here, we briefly introduce the wound healing mechanism, organize the history and the main technologies of 3D bioprinting, and discuss the application as well as the future direction of development of 3D bioprinting technology in the field of wound dressings.
... Besides, the advent of modern techniques such as electrospinning and 3D printing have revolutionised the development of multifunctional bioscaffolds at a minimal cost, making it affordable for users (Masri et al., 2022). The minimal cost of manufacturing refers to printing 5,000 pieces of a physical library of mix-and-match channel scaffolds (100 μm) for USD$ 0.50 and making it available for researchers who lack access to suitable technology (Felton et al., 2021). ...
... A patient with full-thickness burns or other deep skin damage may benefit from the implantation of a multifunctional scaffold made using 3D bioprinting because it allows for the precise placement of cells to repair damaged skin while minimising the number of surgeries and length of the patient's stay. Additionally, it may be possible to manage the geographic integration of multifunctional scaffold and cells in 3D printed skin structures, which could result in a more effective system that speeds up regeneration while possibly requiring less intervention (Masri et al., 2022). Despite being a developed technology, 3D bioprinting suffers from multiple challenges which need to be resolved. ...
Skin tissue engineering possesses great promise in providing successful wound injury and tissue loss treatments that current methods cannot treat or achieve a satisfactory clinical outcome. A major field direction is exploring bioscaffolds with multifunctional properties to enhance biological performance and expedite complex skin tissue regeneration. Multifunctional bioscaffolds are three-dimensional (3D) constructs manufactured from natural and synthetic biomaterials using cutting-edge tissue fabrication techniques incorporated with cells, growth factors, secretomes, antibacterial compounds, and bioactive molecules. It offers a physical, chemical, and biological environment with a biomimetic framework to direct cells toward higher-order tissue regeneration during wound healing. Multifunctional bioscaffolds are a promising possibility for skin regeneration because of the variety of structures they provide and the capacity to customise the chemistry of their surfaces, which allows for the regulated distribution of bioactive chemicals or cells. Meanwhile, the current gap is through advanced fabrication techniques such as computational designing, electrospinning, and 3D bioprinting to fabricate multifunctional scaffolds with long-term safety. This review stipulates the wound healing processes used by commercially available engineered skin replacements (ESS), highlighting the demand for a multifunctional, and next-generation ESS replacement as the goals and significance study in tissue engineering and regenerative medicine (TERM). This work also scrutinise the use of multifunctional bioscaffolds in wound healing applications, demonstrating successful biological performance in the in vitro and in vivo animal models. Further, we also provided a comprehensive review in requiring new viewpoints and technological innovations for the clinical application of multifunctional bioscaffolds for wound healing that have been found in the literature in the last 5 years.
... The hydrophilicity of sodium-alginate-based hydrogel helps to generate a moist wound environment, which speeds up the healing process for skin wounds. Additionally, the changed hydrogel's mechanical properties are indistinguishable from those of healthy skin tissue [205][206][207][208][209]. Homogeneous porous scaffolds can be developed thanks to advancements in 3D bioprinting technology; a pore size of 100-300 m is optimal for cell activity and nutrition transfer [210]. ...
Alginates are polysaccharides that are produced naturally and can be isolated from brown sea algae and bacteria. Sodium alginate (SA) is utilized extensively in the field of biological soft tissue repair and regeneration owing to its low cost, high biological compatibility, and quick and moderate crosslinking. In addition to their high printability, SA hydrogels have found growing popularity in tissue engineering, particularly due to the advent of 3D bioprinting. There is a developing curiosity in tissue engineering with SA-based composite hydrogels and their potential for further improvement in terms of material modification, the molding process, and their application. This has resulted in numerous productive outcomes. The use of 3D scaffolds for growing cells and tissues in tissue engineering and 3D cell culture is an innovative technique for developing in vitro culture models that mimic the in vivo environment. Especially compared to in vivo models, in vitro models were more ethical and cost-effective, and they stimulate tissue growth. This article discusses the use of sodium alginate (SA) in tissue engineering, focusing on SA modification techniques and providing a comparative examination of the properties of several SA-based hydrogels. This review also covers hydrogel preparation techniques, and a catalogue of patents covering different hydrogel formulations is also discussed. Finally, SA-based hydrogel applications and future research areas concerning SA-based hydrogels in tissue engineering were examined.
... These challenges, which were first addressed through replacement, are now being attempted by tissue engineering which seeks to apply stem cell research to developing biology principles to regenerate tissues, cells, and organs (Song et al., 2021). By mimicking micro, nano, and macrostructure (Masri et al., 2022), 3D bioprinting may replicate difficult native-like tissue construction more realistically in the laboratory and prosper in areas where tissue engineering has not been capable of. The capability to bioprint physiologically appropriate multicellular tissue constructs on demand would avoid the essential for autologous tissue harvest and dependency on organ donors over and above transform reconstructive surgery. ...
Congenital heart defect interventions may benefit from the fabrication of patient-specific vascular grafts because of the wide array of anatomies present in children with cardiovascular defects. Three-dimensional (3D) bioprinting is used to establish a platform to produce custom vascular grafts, which are biodegradable , mechanically compatible with vascular tissues, and support neotissue formation and growth. It is an advanced and emerging technology having great potential in the field of tissue engineering. Bioprinting uses cell-laden biomaterials, generally called bio-inks, to deposit in a layer-by-layer fashion. The goal of 3D bioprinting is to offer an alternative to autologous or allogeneic tissue grafts to replace or treat damaged tissues. This chapter aims to offer a synopsis of the current state of 3D bioprinting techniques in analysis, research potentials, and applications. This new and exciting technology has the potential to not only provide better treatment options, but also to improve the quality of life for patients suffering from chronic illnesses.
... Optimal wound healing in adults should comprise four overlapping, continuous phases: inflammation, proliferation, remodeling, and hemostasis. However, chronic wounds with aberrant pathological characteristics result in a slow healing rate, prolonged inflammatory phase, and extensive scar development following recovery [10] . An ideal wound treatment should have better reproducibility, biocompatibility, cell adherence, and acceptable mechanical qualities. ...
3D bioprinting technology is a well-established and promising advanced fabrication technique that utilizes potential biomaterials as bioinks to replace lost skin and promote new tissue regeneration. Cutaneous regenerative biomaterials are highly commended since they benefit patients with larger wound sizes and irregular wound shapes compared to the painstaking split-skin graft. This study aimed to fabricate biocompatible, biodegradable, and printable bioinks as a cutaneous substitute that leads to newly formed tissue post-transplantation. Briefly, gelatin (GE) and polyvinyl alcohol (PVA) bioinks were prepared in various concentrations (w/v); GE (6% GE: 0% PVA), GPVA3 (6% GE: 3% PVA), and GPVA5 (6% GE: 5% PVA), followed by 0.1% (w/v) genipin (GNP) crosslinking to achieve optimum printability. According to the results, GPVA5_GNP significantly presented at least 590.93 ± 164.7% of swelling ratio capacity and optimal water vapor transmission rate (WVTR), which is <1500 g/m2/h to maintain the moisture of the wound microenvironment. Besides, GPVA5_GNP is also more durable than other hydrogels with the slowest biodegradation rate of 0.018 ± 0.08 mg/h. The increasing amount of PVA improved the rheological properties of the hydrogels, leading the GPVA5_GNP to have the highest viscosity, around 3.0 ± 0.06 Pa.s. It allows a better performance of bioinks printability via extrusion technique. Moreover, the cross-section of the microstructure hydrogels showed the average pore sizes >100 μm with excellent interconnected porosity. X-ray diffraction (XRD) analysis showed that the hydrogels maintain their amorphous properties and were well-distributed through energy dispersive X-ray after crosslinking. Furthermore, there had no substantial functional group changes, as observed by Fourier transform infrared spectroscopy, after the addition of crosslinker. In addition, GPVA hydrogels were biocompatible to the cells, effectively demonstrating >90% of cell viability. In conclusion, GPVA hydrogels crosslinked with GNP, as prospective bioinks, exhibited the superior properties necessary for wound healing treatment.
... Sodium alginate-based hydrogel has good biocompatibility, its hydrophilicity can create a moist wound environment for skin wound recovery and accelerate skin recovery. Moreover, the mechanical properties of the modified hydrogel are similar to those of natural skin tissue [208][209][210][211][212]. The development of 3D bioprinting technology provides favorable conditions for the development of homogeneous porous scaffolds, and the general pore size in the range of 100 ~ 300 μm is suitable for cell activity and nutrient transport [213]. In terms of scaffold materials, SA/gelatin blends are the most frequently used biomaterials. ...
Sodium alginate (SA) is an inexpensive and biocompatible biomaterial with fast and gentle crosslinking that has been widely used in biological soft tissue repair/regeneration. Especially with the advent of 3D bioprinting technology, SA hydrogels have been applied more deeply in tissue engineering due to their excellent printability. Currently, the research on material modification, molding process and application of SA-based composite hydrogels has become a hot topic in tissue engineering, and a lot of fruitful results have been achieved. To better help readers have a comprehensive understanding of the development status of SA based hydrogels and their molding process in tissue engineering, in this review, we summarized SA modification methods, and provided a comparative analysis of the characteristics of various SA based hydrogels. Secondly, various molding methods of SA based hydrogels were introduced, the processing characteristics and the applications of different molding methods were analyzed and compared. Finally, the applications of SA based hydrogels in tissue engineering were reviewed, the challenges in their applications were also analyzed, and the future research directions were prospected. We believe this review is of great helpful for the researchers working in biomedical and tissue engineering.
... Further, the role of accurate matrix/cell placement using 3D printing in the development of skin adnexal structure may assist in clinical translation of the technology. 83 There are many considerations involved in the clinical implementation of a 3D printed skin solution. Exploring the current knowledge of tissue engineered skin technologies with a gap analysis, specifically understanding the interplay between cells and their constructed environment and the role of 3D printing. ...
Tissue engineering solutions for skin have been developed over the last few decades with a focus initially on a two-layered structure with epithelial and dermal repair. An essential element of skin restoration is a source of cells capable of differentiating into the appropriate phenotype. The need to repair areas of skin when traditional techniques were not adequate addressed led to cell based therapies being developed initially as a laboratory-based tissue expansion opportunity, both as sheets of cultured epithelial autograft and in composite laboratory-based skin substitutes. The time to availability of the cell-based therapies has been solved in a number of ways, from using allograft cell-based solutions to the use of point of care skin cell harvesting for immediate clinical use. More recently pluripotential cells have been explored providing a readily available source of cells and cells which can express the broad range of phenotypes seen in the mature skin construct. The lessons learnt from the use of cell based techniques has driven the exploration of the use of 3D printing technology, with controlled accurate placement of the cells within a specific printed construct to optimise the phenotypic expression and tissue generation.
