Dense Nanofibrillar Collagen–Silica Hybrids with High Strength and ECM‐Mimetic Tissue Integration

ABSTRACT Collagen, the primary structural protein of the extracellular matrix (ECM), is widely used in biomaterials for tissue engineering and repair. However, its limited mechanical properties constrain its use in load‐bearing applications. Here, we present a strategy to fabricate dense collagen–silica hybrid hydrogels (16 wt.% collagen) that have high mechanical strength, flexibility, printability, and biofunctionality. Using borate‐mediated templating, we synchronize the formation of nanostructured silica networks with collagen fibrillogenesis, and subsequently covalently bind the two phases. This approach yields a compressive modulus ∼1.5 MPa for the hybrid hydrogels with a water content as high as 85%. Characterization confirms that borates act transiently during processing, allowing network formation without being retained in the final material. The hybrid hydrogels support high cell viability, elongation, and alignment in 3D cultures, while in vivo, initially cell‐free scaffolds, implanted subcutaneously display minimal inflammation, vascularized tissue integration, and controlled, cell‐mediated degradation. Taken together, this work establishes a robust framework for creating printable, ECM‐mimetic collagen–silica hybrids with nanoscale reinforcement, offering new opportunities in regenerative medicine and scaffold fabrication.