Abstract
Hydroxyapatite (HA) reinforced collagen fibrils serve as the basic building blocks of natural bone and dentin. Mineralization of collagen fibrils play an essential role in ensuring the structural and mechanical functionalities of hard tissues such as bone and dentin. Biomineralization of collagen can be divided into intrafibrillar and extrafibrillar mineralization in terms of HA distribution relative to collagen fibrils. Intrafibrillar mineralization is termed when HA minerals are incorporated within the gap zone of collagen fibrils, while extrafibrillar mineralization refers to the minerals that are formed on the surface of collagen fibrils. However, the mechanisms resulting in these two types of mineralization still remain debatable. In this review, the evolution of both classical and non-classical biomineralization theories is summarized. Different intrafibrillar mineralization mechanisms, including polymer induced liquid precursor (PILP), capillary action, electrostatic attraction, size exclusion, Gibbs-Donnan equilibrium, and interfacial energy guided theories, are discussed. Exemplary strategies to induce biomimetic intrafibrillar mineralization using non-collagenous proteins (NCPs), polymer analogs, small molecules, and fluidic shear stress are discussed, and recent applications of mineralized collagen fibers for bone regeneration and dentin repair are included. Finally, conclusions are drawn on these proposed mechanisms, and the future trend of collagen-based materials for bone regeneration and tooth repair is speculated.
Highlights
Natural bone is an organic and inorganic composite constituting of mineralized collagen fibrils, which serves as the second level of its seven hierarchical levels
With the evolution of techniques and knowledge, they subsequently confirmed their theory by duplicating similar observations via a combination analyses of transmission electron microscopy (TEM), scanning electron microscopy (SEM), confocal microscopy, and X-ray diffraction (XRD) in a calcium phosphate (CaP) system that is more closely mimicking the nanostructure of natural bone [29,44,53]
Natural bone and dentin are organic-inorganic composites mainly consisting of collagen and HA that are arranged in multilevel hierarchical structures from atomic- to macroscale
Summary
Natural bone is an organic and inorganic composite constituting of mineralized collagen fibrils, which serves as the second level of its seven hierarchical levels. As a naturally extracted polymer from extracellular matrix (ECM), collagen-based materials demonstrate excellent biocompatibility, which supports cellular adhesion, proliferation, migration and differentiation As a result, they have been widely used in many biomedical applications, such as drug delivery, tissue engineering, wound healing, and cosmetic surgery [8,12,13]. There is a need to develop a comprehensive review on these mechanisms, especially to include the most recent progress of biomineralization mechanisms In this review, both intrafibrillar and extrafibrillar mineralization mechanisms are discussed and strategies for biomimetic mineralization of collagen-based materials are reviewed, and their applications in bone tissue engineering and tooth remineralization are covered. The future trend of mineralized collagen-based material in tissue engineering and dentin repair is speculated
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