Bone-like Collagen Matrices Through Rapid Intrafibrillar Mineralisation

An innovative strategy for collagen self-assembly with accelerated intra and extrafibrillar mineralisation is introduced to generate bone scaffolds with biomimetic properties. This method, termed Rapid Fibrillogenic Mineralisation (RFM), leverages coprecipitation with 10× Simulated Body Fluid (10× SBF) during fibril formation to maximise nucleation, particularly within intrafibrillar zones at molecular termini. Densification is achieved within minutes via plastic compression driven by capillary action, producing bone-like scaffold density without compromising the collagen matrix. Transmission electron microscopy confirms intrafibrillar hydroxyapatite crystals within 15 min, while X-ray diffraction demonstrates distinct HA peaks across groups. Scanning electron microscopy verified extrafibrillar mineralisation after 4 h, with saturation by 6 h, yielding 'nanoflower' crystal clusters. Infrared spectra showed increased carbonate content over time, indicating lattice substitutions characteristic of natural bone. Enhanced mineralisation translated into significant mechanical gains as Dynamic Mechanical Analysis revealed compressive moduli approaching cancellous bone (up to 283 ± 31 MPa). In addition, a decrease in the piezoelectric coefficient occurs with increased mineralisation process, highlighting the effects of mineral inclusions on collagen fibre composition and anisotropy. Biologically, mineralised scaffolds supported cellular growth compared to collagen controls. RFM thus enables rapid, reproducible fabrication of biomimetic bone scaffolds that closely emulate native mineralisation patterns and mechanical behaviour. Beyond offering a practical route for scaffold production in tissue engineering, the process also provides new insights into bone physiology and in vitro modelling. By reshaping collagen into a synthetic echo of nature's bone, RFM establishes a rapid approach for designing functional biomaterials with translational potential.