Reconstructive Surgery & Regenerative Medicine Research Group, Institute of Life Science, Swansea University Medical School, Swansea, UK.
Reconstructive Surgery & Regenerative Medicine Research Group, Institute of Life Science, Swansea University Medical School, Swansea, UK; Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, UK.
J Plast Reconstr Aesthet Surg. 2018 May;71(5):615-623. doi: 10.1016/j.bjps.2017.12.006. Epub 2017 Dec 13.
Commercially available tissue engineered skin remains elusive despite extensive research because the multi-stratified anisotropic structure is difficult to replicate in vitro using traditional tissue engineering techniques. Bioprinting, involving computer-controlled deposition of cells and scaffolds into spatially controlled patterns, is able to control not only the macro but also micro and nanoarchitecture and could offer the potential to more faithfully replicate native skin.
We conducted a literature review using PubMed, EMBASE and Web of Science for studies on skin 3D bioprinting between 2009 and 2016, evaluating the bioprinting technique, cell source, scaffold type and in vitro and in vivo outcomes.
We outline the evolution of biological skin replacements, principles of bioprinting and how they apply to the skin tissue engineering field, potential clinical applications as well the current limitations and future avenues for research. Of the studies analysed, the most common types of bioinks consisted of keratinocytes and fibroblasts combined with collagen, although stem cells are gaining increasing recognition. Laser assisted deposition was the most common printing modality, although ink-jet and pneumatic extrusion have also been tested. Bioprinted skin promoted accelerated wound healing, was able to mimic stratified epidermis but not the thick, elastic, vascular dermis.
Although 3D bioprinting shows promise in engineering skin, evidenced by large collective investments from the cosmetic industry, the research is still in its infancy. The resolution, vascularity, optimal cell and scaffold combinations and cost of bioprinted skin are hurdles that need to be overcome before the clinical applicability can be realised. Small scale 3D skin tissue models for cosmetics, drug and toxicity testing as well as tumour modelling are likely to be translated first before we see this technology used in reconstructive surgery patients.
尽管进行了广泛的研究,但仍难以获得商业化的组织工程皮肤,因为使用传统的组织工程技术很难在体外复制具有多层次各向异性结构的皮肤。生物打印技术涉及使用计算机控制细胞和支架在空间上进行受控沉积,不仅能够控制宏观结构,还能够控制微观和纳观结构,从而有可能更忠实地复制天然皮肤。
我们使用 PubMed、EMBASE 和 Web of Science 对 2009 年至 2016 年间的皮肤 3D 生物打印研究进行了文献综述,评估了生物打印技术、细胞来源、支架类型以及体外和体内结果。
我们概述了生物皮肤替代物的发展、生物打印的原理及其在皮肤组织工程领域的应用、潜在的临床应用以及当前的局限性和未来的研究方向。在分析的研究中,最常见的生物墨水类型包括角朊细胞和成纤维细胞与胶原蛋白的组合,尽管干细胞的应用越来越受到关注。激光辅助沉积是最常见的打印方式,但喷墨和气动挤压也已被测试过。生物打印的皮肤促进了伤口的快速愈合,能够模拟分层的表皮,但不能模拟厚而有弹性的血管化真皮。
尽管 3D 生物打印在工程皮肤方面显示出了前景,这得到了化妆品行业的大量投资的证明,但研究仍处于起步阶段。分辨率、血管化、最佳细胞和支架组合以及生物打印皮肤的成本都是需要克服的障碍,只有克服了这些障碍,才能实现其临床应用。用于化妆品、药物和毒性测试以及肿瘤建模的小规模 3D 皮肤组织模型可能会首先得到转化,然后我们才会看到这项技术在重建手术患者中得到应用。