Barnacle-Inspired Integration of Alginate Multilayer Hydrogels Via Calcium Mineralization

Multilayered hydrogels with an organization of distinct functional layers have emerged as the preferred materials for biomedical applications. Taking inspiration from the symbiotic integration of cement proteins and calcified base plates observed in barnacles, we present here an eco-friendly spray-aided approach for creating multilayered alginate/mineral hybrid hydrogels through Ca2+-induced alginate gelation and concurrent mineralization. Electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction analyses confirmed the formation of thin films of CaCO3 or Ca-3(PO4)(2) between the alginate interlayers. Incorporation of calcium minerals was shown to improve considerably the physical properties of alginate multilayer hydrogels, including elasticity and its temperature-responsiveness, porosity, swelling, and liposome release capability (as a drug release model). Moreover, comprehensive in vitro and in vivo evaluations using NIH-3T3 cells, a rat model, and rabbit whole blood demonstrated good biocompatibility and procoagulant activity of the alginate/mineral multilayer hydrogels. Notably, the integration of Ca-3(PO4)(2) with an alginate multilayer outperformed CaCO3 in all aforementioned physical and procoagulant properties. Hence, the combination of mineralization (especially Ca-3(PO4)(2)) with alginate multilayer structuring exhibits significant potential for various healthcare applications. This biomimetic green strategy can also be adapted readily for the sustainable fabrication of other organic-inorganic multilayers with alginate-like polyanionic polymers and calcium minerals.