Kumari Sushma, Bargel Hendrik, Anby Mette U, Lafargue David, Scheibel Thomas
Lehrstuhl Biomaterialien, Fakultät für Ingenieurwissenschaften, Universität Bayreuth, Universitätsstraße 30, 95440 Bayreuth, Germany.
Technologie Servier, 25/27 rue Eugène Vignat, 45000 Orleans, France.
ACS Biomater Sci Eng. 2018 May 14;4(5):1750-1759. doi: 10.1021/acsbiomaterials.8b00382. Epub 2018 Apr 16.
Therapeutic biologics (i.e., proteins) have been widely recognized for the treatment, prevention, and cure of a variety of human diseases and syndromes. However, design of novel protein-delivery systems to achieve a nontoxic, constant, and efficient delivery with minimal doses of therapeutic biologics is still challenging. Here, recombinant spider silk-based materials are employed as a delivery system for the administration of therapeutic biologicals. Hydrogels made of the recombinant spider silk protein eADF4(C16) were used to encapsulate the model biologicals BSA, HRP, and LYS by direct loading or through diffusion, and their release was studied. Release of model biologicals from eADF4(C16) hydrogels is in part dependent on the electrostatic interaction between the biological and the recombinant spider silk protein variant used. In addition, tailoring the pore sizes of eADF4(C16) hydrogels strongly influenced the release kinetics. In a second approach, a particles-in-hydrogel system was used, showing a prolonged release in comparison with that of plain hydrogels (from days to week). The particle-enforced spider silk hydrogels are injectable and can be 3D printed. These initial studies indicate the potential of recombinant spider silk proteins to design novel injectable hydrogels that are suitable for delivering therapeutic biologics.
治疗性生物制品（即蛋白质）在治疗、预防和治愈各种人类疾病及综合征方面已得到广泛认可。然而，设计新型蛋白质递送系统以实现用最小剂量的治疗性生物制品进行无毒、持续且高效的递送仍然具有挑战性。在此，基于重组蜘蛛丝的材料被用作治疗性生物制品给药的递送系统。由重组蜘蛛丝蛋白eADF4(C16)制成的水凝胶通过直接加载或扩散用于包封模型生物制品牛血清白蛋白（BSA）、辣根过氧化物酶（HRP）和赖氨酸（LYS），并对它们的释放进行了研究。模型生物制品从eADF4(C16)水凝胶中的释放部分取决于生物制品与所使用的重组蜘蛛丝蛋白变体之间的静电相互作用。此外，调整eADF4(C16)水凝胶的孔径对释放动力学有很大影响。在第二种方法中，使用了水凝胶包颗粒系统，与普通水凝胶相比，其显示出延长的释放（从数天到数周）。颗粒增强的蜘蛛丝水凝胶是可注射的，并且可以进行3D打印。这些初步研究表明重组蜘蛛丝蛋白在设计适用于递送治疗性生物制品的新型可注射水凝胶方面的潜力。
