Evaluation of the osteoinductive potential of a bio-inspired scaffold mimicking the osteogenic niche for bone augmentation

Augmentation of regenerative osteogenesis represents a premier clinical need, as hundreds of thousands of patients are left with insufficient healing of bony defects related to a host of insults ranging from congenital abnormalities to traumatic injury to surgically-induced deficits. A synthetic material that closely mimics the composition and structure of the human osteogenic niche represents great potential to successfully address this high demand. In this study, a magnesium-doped hydroxyapatite/type I collagen scaffold was fabricated through a biologically-inspired mineralization process and designed to mimic human trabecular bone. The composition of the scaffold was fully characterized by XRD, FTIR, ICP and TGA, and compared to human bone. Also, the scaffold microstructure was evaluated by SEM, while its nano-structure and nano-mechanical properties were evaluated by AFM. Human bone marrow-derived mesenchymal stem cells were used to test the in vitro capability of the scaffold to promote osteogenic differentiation. The cell/scaffold constructs were cultured up to 7 days and the adhesion, organization and proliferation of the cells were evaluated. The ability of the scaffold to induce osteogenic differentiation of the cells was assessed over 3 weeks and the correlate gene expression for classic genes of osteogenesis was assessed. Finally, when tested in an ectopic model in rabbit, the scaffold produced a large volume of trabecular bone in only two weeks, that subsequently underwent maturation over time as expected, with increased mature cortical bone formation, supporting its ability to promote bone regeneration in clinically-relevant scenarios. Altogether, these results confirm a high level of structural mimicry by the scaffold to the composition and structure of human osteogenic niche that translated to faster and more efficient osteoinduction in vivo – features that suggest such a biomaterial may have great utility in future clinical applications where bone regeneration is required

From wood to bone: multi-step process to convert wood hierarchical structures into biomimetic hydroxyapatite scaffolds for bone tissue engineering

Hydroxyapatite (HA) bone scaffolds characterized by highly organized hierarchical structures have been obtained by chemically transforming native woods through a sequence of thermal and hydrothermal processes. The whole chemical conversion has been carried out through five steps from native wood to porous hydroxyapatite: 1) pyrolysis of ligneous raw materials to produce carbon templates characterized by the natural complex anisotropic pore structure; 2) carburization process by vapour or liquid calcium permeation to yield calcium carbide; 3) oxidation process to transform calcium carbide into calcium oxide; 4) carbonation by hydrothermal process under CO2 pressure for the further conversion into calcium carbonate; 5) phosphatization process through hydrothermal treatment to achieve the final hydroxyapatite phase. The five steps of the phase transformation process have been set up in order to achieve total phase conversion and purity maintaining the original native microstructure. An innovative biomimetic apatite hierarchically structured in parallel fastened hollow microtubules has been synthesized, structurally characterized and proposed as a new inorganic biomorphic scaffold providing a biomimetic nanostructure surface for fascinating bone engineering applications.

Nature’s hierarchical materials

Many biological tissues, such as wood and bone, are fiber composites with a hierarchical structure. Their exceptional mechanical properties are believed to be due to a functional adaptation of the structure at all levels of hierarchy. This article reviews the basic principles involved in designing hierarchical biological materials, such as cellular and composite architectures, adapative growth and as well as remodeling. Some examples that are found to utilize these strategies include wood, bone, tendon, and glass sponges – all of which are discussed.

Bioinspired structural materials

Natural structural materials are built at ambient temperature from a fairly limited selection of components. They usually comprise hard and soft phases arranged in complex hierarchical architectures, with characteristic dimensions spanning from the nanoscale to the macroscale. The resulting materials are lightweight and often display unique combinations of strength and toughness, but have proven difficult to mimic synthetically. Here, we review the common design motifs of a range of natural structural materials, and discuss the difficulties associated with the design and fabrication of synthetic structures that mimic the structural and mechanical characteristics of their natural counterparts

Study of the hydrothermal transformation of wood-derived calcium carbonate into 3D hierarchically organized hydroxyapatite

The aim of this work was to achieve a procedure that could totally transform calcium carbonate template derived from wood (Calamus Manna or rattan) into a biomimetic hydroxyapatite scaffold, yet preserving its original hierarchical architecture.The biomorphic conversion was investigated in depth under hydrothermal treatment at low temperatures and with different phosphate solutions. A kinetic approach was used to follow the rates and mechanisms of transformation. Diffusion controlled process and nuclei-one dimensional growth of hydroxyapatite were defined. The results showed the successful transformation, which was accomplished after 96 h in basic pH conditions at temperatures ranging between 20 and 60 °C. The resulting scaffold preserved the initial structure of rattan, featuring ideal pore size and interconnectivity for a spongy bone substitute. In the future, these biomorphic processes on natural woods could be useful for the development of biomedical devices for long bone substitute, having high biomechanical performance and regenerative properties.

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