Veiseh Omid, Doloff Joshua C, Ma Minglin, Vegas Arturo J, Tam Hok Hei, Bader Andrew R, Li Jie, Langan Erin, Wyckoff Jeffrey, Loo Whitney S, Jhunjhunwala Siddharth, Chiu Alan, Siebert Sean, Tang Katherine, Hollister-Lock Jennifer, Aresta-Dasilva Stephanie, Bochenek Matthew, Mendoza-Elias Joshua, Wang Yong, Qi Merigeng, Lavin Danya M, Chen Michael, Dholakia Nimit, Thakrar Raj, Lacík Igor, Weir Gordon C, Oberholzer Jose, Greiner Dale L, Langer Robert, Anderson Daniel G
1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [3] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
1] David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA [2] Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Ave, Boston, Massachusetts 02115, USA.
Nat Mater. 2015 Jun;14(6):643-51. doi: 10.1038/nmat4290. Epub 2015 May 18.
The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals and plastics, significantly abrogated foreign body reactions and fibrosis when compared with smaller spheres. We also show that for encapsulated rat pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6 mice, islets prepared in 1.5-mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than five times longer than for transplanted grafts encapsulated within conventionally sized 0.5-mm alginate capsules. Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved simply by tuning their spherical dimensions.
植入式生物医学设备的功效常常因宿主识别及随后的异物反应而受损。在此,我们展示了植入材料的几何形状对其体内生物相容性的作用。在啮齿动物和非人类灵长类动物模型中,与较小的球体相比,植入直径1.5毫米及以上、涵盖多种材料(包括水凝胶、陶瓷、金属和塑料)的球体,能显著消除异物反应和纤维化。我们还表明,对于移植到经链脲佐菌素处理的糖尿病C57BL/6小鼠体内的封装大鼠胰岛细胞,置于1.5毫米藻酸盐胶囊中的胰岛能够将血糖控制恢复长达180天,这一时期比置于传统尺寸0.5毫米藻酸盐胶囊中的移植移植物的时间长五倍多。我们的研究结果表明,仅通过调整生物医学设备的球形尺寸就能显著提高其体内生物相容性。