Abaci Hasan E, Guo Zongyou, Coffman Abigail, Gillette Brian, Lee Wen-Han, Sia Samuel K, Christiano Angela M
Department of Dermatology, Columbia University Medical Center, NY, 10032, USA.
Department of Biomedical Engineering, Columbia University, NY, 10032, USA.
Adv Healthc Mater. 2016 Jul;5(14):1800-7. doi: 10.1002/adhm.201500936. Epub 2016 Jun 22.
Vascularization of engineered human skin constructs is crucial for recapitulation of systemic drug delivery and for their long-term survival, functionality, and viable engraftment. In this study, the latest microfabrication techniques are used and a novel bioengineering approach is established to micropattern spatially controlled and perfusable vascular networks in 3D human skin equivalents using both primary and induced pluripotent stem cell (iPSC)-derived endothelial cells. Using 3D printing technology makes it possible to control the geometry of the micropatterned vascular networks. It is verified that vascularized human skin equivalents (vHSEs) can form a robust epidermis and establish an endothelial barrier function, which allows for the recapitulation of both topical and systemic delivery of drugs. In addition, the therapeutic potential of vHSEs for cutaneous wounds on immunodeficient mice is examined and it is demonstrated that vHSEs can both promote and guide neovascularization during wound healing. Overall, this innovative bioengineering approach can enable in vitro evaluation of topical and systemic drug delivery as well as improve the potential of engineered skin constructs to be used as a potential therapeutic option for the treatment of cutaneous wounds.
工程化人皮肤构建体的血管化对于重现全身药物递送以及其长期存活、功能和可行的移植至关重要。在本研究中，使用了最新的微制造技术，并建立了一种新颖的生物工程方法，以在3D人皮肤等效物中使用原代和诱导多能干细胞（iPSC）衍生的内皮细胞对空间可控且可灌注的血管网络进行微图案化。使用3D打印技术能够控制微图案化血管网络的几何形状。已证实血管化人皮肤等效物（vHSE）可形成坚固的表皮并建立内皮屏障功能，这使得能够重现局部和全身药物递送。此外，还研究了vHSE对免疫缺陷小鼠皮肤伤口的治疗潜力，并证明vHSE在伤口愈合过程中既能促进又能引导新生血管形成。总体而言，这种创新的生物工程方法能够实现对局部和全身药物递送的体外评估，并提高工程化皮肤构建体作为治疗皮肤伤口潜在治疗选择的潜力。
