Abstract:Based on the 3D printing technologies and the concepts developed in tissue engineering during the last decades, 3D bioprinting is emerging as the most innovative and promising technology for the generation of human tissues and organs. In the case of skin bioprinting, thanks to the research process carried out during the last years, interfollicular skin has been printed with a structural and functional quality that paves the way for clinical and industrial applications. This review analyzes the present achievem… Show more
“…Compared with non-biological 3D printing, technical challenges related to the sensitivity of living cells to the shear stress during the bioprinting process can be found [151], which requires the integration of knowledge in the fields of engineering, biomaterials science, cell biology, and physics. Bioprinting techniques have already been proposed for the fabrication of 3D hydrogel-based structures, envisioning several tissue transplantations or substitutions, including skin [152], bone [153], vascular grafts [154], intervertebral disc (IVD) [102], meniscus, and cartilage [155]. More recently, the development of high-throughput in vitro platforms of healthy and diseased tissues of the human body came to address the TE field to a different level of precision medicine [156], and the 3D bioprinted hydrogels emerged as highly precise biomimetic matrices [157].…”
Section: Scaffolding Strategies For Tissue Engineering and Regenermentioning
During the past two decades, tissue engineering and the regenerative medicine field have invested in the regeneration and reconstruction of pathologically altered tissues, such as cartilage, bone, skin, heart valves, nerves and tendons, and many others. The 3D structured scaffolds and hydrogels alone or combined with bioactive molecules or genes and cells are able to guide the development of functional engineered tissues, and provide mechanical support during in vivo implantation. Naturally derived and synthetic polymers, bioresorbable inorganic materials, and respective hybrids, and decellularized tissue have been considered as scaffolding biomaterials, owing to their boosted structural, mechanical, and biological properties. A diversity of biomaterials, current treatment strategies, and emergent technologies used for 3D scaffolds and hydrogel processing, and the tissue-specific considerations for scaffolding for Tissue engineering (TE) purposes are herein highlighted and discussed in depth. The newest procedures focusing on the 3D behavior and multi-cellular interactions of native tissues for further use for in vitro model processing are also outlined. Completed and ongoing preclinical research trials for TE applications using scaffolds and hydrogels, challenges, and future prospects of research in the regenerative medicine field are also presented.
“…Compared with non-biological 3D printing, technical challenges related to the sensitivity of living cells to the shear stress during the bioprinting process can be found [151], which requires the integration of knowledge in the fields of engineering, biomaterials science, cell biology, and physics. Bioprinting techniques have already been proposed for the fabrication of 3D hydrogel-based structures, envisioning several tissue transplantations or substitutions, including skin [152], bone [153], vascular grafts [154], intervertebral disc (IVD) [102], meniscus, and cartilage [155]. More recently, the development of high-throughput in vitro platforms of healthy and diseased tissues of the human body came to address the TE field to a different level of precision medicine [156], and the 3D bioprinted hydrogels emerged as highly precise biomimetic matrices [157].…”
Section: Scaffolding Strategies For Tissue Engineering and Regenermentioning
During the past two decades, tissue engineering and the regenerative medicine field have invested in the regeneration and reconstruction of pathologically altered tissues, such as cartilage, bone, skin, heart valves, nerves and tendons, and many others. The 3D structured scaffolds and hydrogels alone or combined with bioactive molecules or genes and cells are able to guide the development of functional engineered tissues, and provide mechanical support during in vivo implantation. Naturally derived and synthetic polymers, bioresorbable inorganic materials, and respective hybrids, and decellularized tissue have been considered as scaffolding biomaterials, owing to their boosted structural, mechanical, and biological properties. A diversity of biomaterials, current treatment strategies, and emergent technologies used for 3D scaffolds and hydrogel processing, and the tissue-specific considerations for scaffolding for Tissue engineering (TE) purposes are herein highlighted and discussed in depth. The newest procedures focusing on the 3D behavior and multi-cellular interactions of native tissues for further use for in vitro model processing are also outlined. Completed and ongoing preclinical research trials for TE applications using scaffolds and hydrogels, challenges, and future prospects of research in the regenerative medicine field are also presented.
“…These bilayered skin grafts have been successfully used to treat burns, as well as traumatic and surgical wounds in a large number of patients in Spain and for the generation of skin‐humanized mouse models (Guerrero‐Aspizua et al, 2010; Llames et al, 2004; Llames et al, 2006; Martinez‐Santamaria et al, 2013). Our lab has also developed a complete system (printer and bioinks) to 3D print this bilayered skin for clinical and commercial testing purposes (Cubo, Garcia, del Canizo, Velasco, & Jorcano, 2016; Velasco, Quílez, Garcia, del Cañizo, & Jorcano, 2018). In general, these skin substitutes formed by two layers, representing the dermis and the epidermis, were generated following the method developed in (Meana et al, 1998).…”
It is well‐known that fibroblasts play a fundamental role in the contraction of collagen and fibrin hydrogels when used in the production of in vitro bilayered skin substitutes. However, little is known about the contribution of other factors, such as the hydrogel matrix itself, on this contraction. In this work, we studied the contraction of plasma‐derived fibrin hydrogels at different temperatures (4, 23, and 37°C) in an isotonic buffer (phosphate‐buffered saline). These types of hydrogels presented a contraction of approximately 30% during the first 24 hr, following a similar kinetics irrespectively of the temperature. This kinetics continued in a slowed down manner to reach a plateau value of 40% contraction after 10–15 days. Contraction of commercial fibrinogen hydrogels was studied under similar conditions and the kinetics was completed after 8 hr, reaching values between 20 and 70% depending on the temperature. We attribute these substantial differences to a modulatory effect on the contraction due to plasma proteins which are initially embedded in, and progressively released from, the plasma‐based hydrogels. The elastic modulus of hydrogels measured at a constant frequency decreased with increasing temperature in 7‐day gels. Rheological measurements showed the absence of a strain‐hardening behavior in the plasma‐derived fibrin hydrogels. Finally, plasma‐derived fibrin hydrogels with and without human primary fibroblast and keratinocytes were prepared in transwell inserts and their height measured over time. Both cellular and acellular gels showed a height reduction of 30% during the first 24 hr likely due to the above‐mentioned intrinsic fibrin matrix contraction.
“…Following the 3Rs principles and with the rise of the biomedical engineering discipline, several in vitro artificial skin models with attractive versatility and reproducibility are being commercialized or under development to reflect the three-dimensional environment of human native skin and the in vivo drug release conditions through the skin barrier [ 39 ]. 3D-bioprinting has emerged as an ideal technology to design more complex artificial skin models under automatized and standardized protocols able to mimic the native skin in a more reproducible manner [ 40 ]. The versatility of 3D-bioprinting has high translational and clinical relevance, since this technology can be exploited to produce not only full-thickness healthy skin, but also damaged skin under different pathological situations like acute and chronic wounds [ 41 ].…”
The delivery of bioactive agents using active wound dressings for the management of pain and infections offers improved performances in the treatment of wound complications. In this work, solid lipid microparticles (SLMPs) loaded with lidocaine hydrochloride (LID) were processed and the formulation was evaluated regarding its ability to deliver the drug at the wound site and through the skin barrier. The SLMPs of glyceryl monostearate (GMS) were prepared with different LID contents (0, 1, 2, 4, and 10 wt.%) using the solvent-free and one-step PGSS (Particles from Gas-Saturated Solutions) technique. PGSS exploits the use of supercritical CO2 (scCO2) as a plasticizer for lipids and as pressurizing agent for the atomization of particles. The SLMPs were characterized in terms of shape, size, and morphology (SEM), physicochemical properties (ATR-IR, XRD), and drug content and release behavior. An in vitro test for the evaluation of the influence of the wound environment on the LID release rate from SLMPs was studied using different bioengineered human skin substitutes obtained by 3D-bioprinting. Finally, the antimicrobial activity of the SLMPs was evaluated against three relevant bacteria in wound infections (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa). SLMPs processed with 10 wt.% of LID showed a remarkable performance to provide effective doses for pain relief and preventive infection effects.
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