Michel Raphaël, Roquart Maïlie, Llusar Elodie, Gaslain Fabrice, Norvez Sophie, Baik Jae Seon, Yi Gi-Ra, Manassero Mathieu, Corté Laurent
Molecular, Macromolecular Chemistry, and Materials, ESPCI Paris, CNRS, PSL Research University, 75005 Paris, France.
Centre des Matériaux, MINES ParisTech, CNRS, PSL Research University, 91003 Evry, France.
ACS Appl Bio Mater. 2020 Dec 21;3(12):8808-8819. doi: 10.1021/acsabm.0c01158. Epub 2020 Nov 10.
The fixation of hydrogels to biological tissues is a major challenge conditioning the development of implants and surgical techniques. Here, coatings of procoagulant nanoparticles are devised which use the presence of blood to create adhesion between hydrogels and soft internal organs. Those nanostructured coatings are simply adsorbed at the hydrogel surfaces and can rapidly activate the formation of an interfacial blood clot acting as an adhesive joint. This concept is demonstrated on pig liver capsules with model poly(ethylene-glycol) membranes that are intrinsically poorly adhesive. In the absence of blood, ex vivo peeling tests show that coatings with aggregates of bare silica nanoparticles induce a 2- to 4-fold increase in adhesion energy as compared to the uncoated membrane (3 ± 2 J m). This effect is found to scale with the specific surface area of the coating. The highest adhesion energies produced by these nanoparticle-coated membranes (10 ± 5 J m) approach the value obtained with cyanoacrylate glue (33 ± 11 J m) for which tearing of the tissue is observed. Ex vivo pull-off tests show an adhesion strength of coated membranes around 5 ± 1 kPa, which is significantly reduced when operating in vivo (1.0 ± 0.5 kPa). Nevertheless, when blood is introduced at the interface, the in vivo adhesion strength can be improved remarkably with silica coatings, reaching 4 ± 2 kPa after 40 min contact. In addition, these silica-coated membranes can seal and stop the bleeding produced by liver biopsies very rapidly (<30 s). Such a combination of coagulation and particle bridging opens promising routes for better biointegrated hydrogel implants and improved surgical adhesives, hemostats, and sealants.
水凝胶与生物组织的固定是制约植入物和外科技术发展的一项重大挑战。在此，设计了促凝血纳米颗粒涂层，该涂层利用血液的存在在水凝胶与柔软内部器官之间形成黏附。这些纳米结构涂层简单地吸附在水凝胶表面，能够迅速激活界面血凝块的形成，起到黏附连接的作用。这一概念在具有本质上黏附性较差的聚（乙二醇）模型膜的猪肝包膜上得到了验证。在没有血液的情况下，体外剥离试验表明，与未涂层的膜（3±2 J/m²）相比，含有裸露二氧化硅纳米颗粒聚集体的涂层使黏附能增加了2至4倍。发现这种效应与涂层的比表面积成比例。这些纳米颗粒涂层膜产生的最高黏附能（10±5 J/m²）接近用氰基丙烯酸酯胶水（33±11 J/m²）获得的值，使用该胶水时会观察到组织撕裂。体外拉脱试验表明，涂层膜的黏附强度约为5±1 kPa，在体内操作时显著降低（1.0±0.5 kPa）。然而，当在界面引入血液时，二氧化硅涂层可显著提高体内黏附强度，接触40分钟后达到4±2 kPa。此外，这些二氧化硅涂层膜能够非常迅速地（<30秒）密封并止住肝活检产生的出血。这种凝血与颗粒桥接的组合为更好的生物集成水凝胶植入物以及改进的手术黏合剂、止血剂和密封剂开辟了有前景的途径。
