Dense fibrillar collagen-based hydrogels as functional osteoid-mimicking scaffolds
Gabriele Griffanti, Showan N. Nazhat
Abstract
There is an increasing need to generate novel materials for the treatment and augmentation of bone defects, affecting millions of people worldwide. Fibrillar type I collagen is the most abundant tissue matrix protein in bone, providing its key native scaffolding material. However, while in vitro reconstituted collagen hydrogels of physically entangled, nano-fibred meshes, have long served as three-dimensional cultures, their highly-hydrated nature impacts their physiological relevance. In an effort to create biomimetic collagen gels, approaches have been undertaken to generate osteoid-like environments with increased collagen concentrations, controlled fibrillar orientation, defined micro-architectures, and tailored mechanical properties. This review describes the state-of-the-art on collagen densification techniques, exploring their advantages, limitations and future perspectives for applications as bone grafts. Ultimately, by successfully mimicking the organic milieu of bone through acellular or cell-mediated mineralisation of the designed osteoid-like structure, functional collagen scaffolds with potential applications in bone tissue engineering can be realised.Abbreviations: 3D: three-dimensional; BG: bioactive glass; CFD: collagen fibrillar density; CHA: carbonated-hydroxyapatite; Col1: Type I collagen; ECM: extracellular matrix; GAE: gel aspiration-ejection; HHC: highly hydrated collagen; MSC: mesenchymal stem cell; NCPs: non-collagenous proteins; PC: plastic compression; PILP: polymer-induced liquid precursor; SBF: simulated body fluid