Bone biomaterials and interactions with stem cells

Bone biomaterials play a vital role in bone repair by providing the necessary substrate for cell adhesion, proliferation, and differentiation and by modulating cell activity and function. In past decades, extensive efforts have been devoted to developing bone biomaterials with a focus on the following issues： （1） developing ideal biomaterials with a combination of suitable biological and mechanical properties; （2） constructing a cell microenvironment with pores ranging in size from nanoscale to submicro- and microscale; and （3） inducing the oriented differentiation of stem cells for artificial-to-biological transformation. Here we present a comprehensive review of the state of the art of bone biomaterials and their interactions with stem cells. Typical bone biomaterials that have been developed, including bioactive ceramics, biodegradable polymers, and biodegradable metals, are reviewed, with an emphasis on their characteristics and applications. The necessary porous structure of bone biomaterials for the cell microenvironment is discussed, along with the corresponding fabrication methods. Additionally, the promising seed stem cells for bone repair are summarized, and their interaction mechanisms with bone biomaterials are discussed in detail. Special attention has been paid to the signaling pathways involved in the focal adhesion and osteogenic differentiation of stem cells on bone biomaterials. Finally, achievements regarding bone biomaterials are summarized, and future research directions are proposed.

Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells

Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate （CAP） biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review： nanostructured calcium phosphate cement （CPC）; nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/ morphology, differentiation and in vivo bone regeneration. Several trends can be seen： （i） nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; （ii） the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; （iii） nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; （iv） combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and （v） cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.

Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration

It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells(MSCs).However,the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear.This study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on scaffolds.Cyclic mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7,14,or 21 days.At the predetermined time points,culture supernatant was collected for inflammatory mediator detection,and gene expression was analyzed by qRT-PCR.The results showed that the expression of inflammatory mediators(IL1B and IL8)was downregulated(p<0.05)and the expression of ALP(p<0.01)and COL1A1(p<0.05)was upregulated under mechanical loading.The cell-scaffold composites biofabricated with or without mechanical loading were freeze-dried to prepare extracellular matrix-based scaffolds(ECM-based scaffolds).Murine macrophages were seeded on the ECM-based scaffolds to evaluate their polarization.The ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying enhanced the expression of M2 polarization-related biomarkers(Arginase 1 and Mrc1,p<0.05)of macrophages in vitro and increased bone volume/total volume ratio in vivo.Overall,these findings demonstrated that mechanical loading could dually modulate the inflammatory responses and osteogenic differentiation of MSCs.Besides,the ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying facilitated the M2 polarization of macrophages in vitro and bone regeneration in vivo.Mechanical loading may be a promising biofabrication strategy for bone biomaterials.

Heparan-mimetics:Potential agents of tissue regeneration for bone and periodontal therapies

Heparan sulfate glycosaminoglycans are key players of tissue repair and can be regarded as useful compounds for regenerative medicines.Unfortunately,their therapeutic uses face many technical,industrial,and regulatory hurdles due to their animal origin.So,some non-animal sulfated polysaccharides mimic heparan sulfate properties and offer interesting solutions to replace them.Among them,dextran derivatives,seaweed polysaccharides,or marine bacterial polysaccharides are the best known and have demonstrated their pro-regenerative capabilities by promoting both extracellular matrix structuring and angiogenesis and limiting degenerative processes such as inflammatory cell migration or tissue proteolysis.These polysaccharides have also shown their ability to specifically promote osteoblastic differentiation and bone wound healing.Furthermore,recent works shows that heparan-mimetics can be used as an additive to improve the cytocompatibility of bone substitutes commonly used in periodontal surgery.The use of these polysaccharides can be regarded as a clever approach to improve the biointegration of bone substitutes.

Preparation and Characterization of Hydroxyapatite-Coated Selenium Nanoparticles and their Interaction with Osteosarcoma(SaOS-2) Cells

Nanotechnology has taken a firm step to revolutionize the field of orthopedic implants. Current research on bone implants focuses to develop implants with multifaceted functions viz., osteoinduction, chemoprevention, antimicrobial action etc., especially for cancerous bone resection. The objective of the present study was to synthesize a novel composite for bone implants, possessing the above properties. Selenium was selected owing to its chemopreventive and chemotherapeutic properties. Hydroxyapatite was selected owing to its bioactivity and similarity in composition to bone mineral properties. Selenium nanoparticles were prepared by chemical reduction method and coated with hydroxyapatite.Hydroxyapatite-coated selenium nanoparticle（HASnp） was characterized physico-chemically using fourier transform infrared spectroscopy, X-ray diffractometry, scanning electron microscope, and energy-dispersive X-ray spectroscopy.HASnp was analysed in vitro using SaOS-2 cell line. Enhanced cell proliferation and alkaline phosphatase activity were observed in HASnp-treated cells. The results indicate that HASnp is highly suitable for the use in orthopedic applications.