Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fillers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specific degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specific biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed.

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Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review.

Silk scaffolds in bone tissue engineering: An overview.

Strategies to improve chitosan hemocompatibility: A review

Despite considerable advances in microsurgical techniques over the past decades, bone tissue remains a challenging arena to obtain a satisfying functional and structural restoration after damage. Through the production of substituting materials mimicking the physical and biological properties of the healthy tissue, tissue engineering strategies address an urgent clinical need for therapeutic alternatives to bone autografts. By virtue of their structural versatility, polymers have a predominant role in generating the biodegradable matrices that hold the cells in situ to sustain the growth of new tissue until integration into the transplantation area (i.e., scaffolds). As compared to synthetic ones, polymers of natural origin generally present superior biocompatibility and bioactivity. Their assembly and further engineering give rise to a wide plethora of advanced supporting materials, accounting for systems based on hydrogels or scaffolds with either fibrous or porous architecture. The present review offers an overview of the various types of natural polymers currently adopted in bone tissue engineering, describing their manufacturing techniques and procedures of functionalization with active biomolecules, and listing the advantages and disadvantages in their respective use in order to critically compare their actual applicability potential. Their combination to other classes of materials (such as micro and nanomaterials) and other innovative strategies to reproduce physiological bone microenvironments in a more faithful way are also illustrated. The regeneration outcomes achieved in vitro and in vivo when the scaffolds are enriched with different cell types, as well as the preliminary clinical applications are presented, before the prospects in this research field are finally discussed. The collection of studies herein considered confirms that advances in natural polymer research will be determinant in designing translatable materials for efficient tissue regeneration with forthcoming impact expected in the treatment of bone defects.

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Natural Polymeric Scaffolds in Bone Regeneration

Hierarchically designed bone scaffolds: From internal cues to external stimuli

Fine structure study on low concentration zinc substituted hydroxyapatite nanoparticles

A novel bi-template induced co-assembly method was employed to fabricate biomimetic bone substitute materials, collagen (COL)-fibroin/hydroxyapatite (COL-SF/HA) composite by using a combination of Type I COL and silk fibroin (SF) molecular templates. As a control, COL/HA and SF/HA composites were also synthesized via single-template assembly technology. The structure and morphology of the resulting assembly composites were investigated by X-ray diffractometer, Fourier transform infrared spectra, transmission electron microscope, and thermogravimetric analysis. Their sizes and size distributions were measured by DLS. The results indicated that the mineral phases in COL-SF/HA, COL-HA, and SF-HA composites were needle-like nano-HA crystals. In comparison to those in COL-HA and SF-HA, the mineral phase in COL-SF/HA displayed smaller size and more narrow distribution. Of all above biomimetic composites, the HA was well assembled with molecular template(s), and the organic content of the composite was about 12%-20%, which was quite similar to the natural bone in composition. CD and SDS-PAGE were used to examine the secondary structure and subunit composition of template proteins. The results revealed that the spatial structure of co-assembly template proteins played a pivotal role in controlling and regulating HA crystal nucleation and growth. Based on the experimental results above, a possible co-assembly mechanism for the HA growing on fibrous bi-template proteins was suggested.

Wei Hu

Papers

Fine structure study on low concentration zinc substituted hydroxyapatite nanoparticles

Collagen/silk fibroin bi‐template induced biomimetic bone‐like substitutes

Dual-functional composite with anticoagulant and antibacterial properties based on heparinized silk fibroin and chitosan

Dual-functional composite with anticoagulant and antibacterial properties based on heparinized silk fibroin and chitosan B Biointerfaces

Antibacterial Electrospun Nanofibrous Materials for Wound Healing