The stem cell/material interface is a complex, dynamic microenvironment in which the cell and the material cooperatively dictate one another's fate: the cell by remodelling its surroundings, and the material through its inherent properties (such as adhesivity, stiffness, nanostructure or degradability). Stem cells in contact with materials are able to sense their properties, integrate cues via signal propagation and ultimately translate parallel signalling information into cell fate decisions. However, discovering the mechanisms by which stem cells respond to inherent material characteristics is challenging because of the highly complex, multicomponent signalling milieu present in the stem cell environment. In this Review, we discuss recent evidence that shows that inherent material properties may be engineered to dictate stem cell fate decisions, and overview a subset of the operative signal transduction mechanisms that have begun to emerge. Further developments in stem cell engineering and mechanotransduction are poised to have substantial implications for stem cell biology and regenerative medicine.

/pdf/materials-as-stem-cell-regulators-e55d1lh2ny.pdf

Materials as stem cell regulators

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.

/pdf/bone-biomaterials-and-interactions-with-stem-cells-4c9eg43ssz.pdf

Bone biomaterials and interactions with stem cells.

Joint replacement is a major orthopaedic procedure used to treat joint osteoarthritis. Aseptic loosening and infection are the two most significant causes of prosthetic implant failure. The ideal implant should be able to promote osteointegration, deter bacterial adhesion and minimize prosthetic infection. Recent developments in material science and cell biology have seen the development of new orthopaedic implant coatings to address these issues. Coatings consisting of bioceramics, extracellular matrix proteins, biological peptides or growth factors impart bioactivity and biocompatibility to the metallic surface of conventional orthopaedic prosthesis that promote bone ingrowth and differentiation of stem cells into osteoblasts leading to enhanced osteointegration of the implant. Furthermore, coatings such as silver, nitric oxide, antibiotics, antiseptics and antimicrobial peptides with anti-microbial properties have also been developed, which show promise in reducing bacterial adhesion and prosthetic infections. This review summarizes some of the recent developments in coatings for orthopaedic implants.

/pdf/bioactive-coatings-for-orthopaedic-implants-recent-trends-in-3z73ss5xy7.pdf

Bioactive Coatings for Orthopaedic Implants—Recent Trends in Development of Implant Coatings

Bioactive glasses caused a revolution in healthcare and paved the way for modern biomaterial-driven regenerative medicine. The first 45S5 glass composition, invented by Larry Hench fifty years ago, was able to bond to living bone and to stimulate osteogenesis through the release of biologically-active ions. 45S5-based glass products have been successfully implanted in millions of patients worldwide, mainly to repair bone and dental defects and, over the years, many other bioactive glass compositions have been proposed for innovative biomedical applications, such as soft tissue repair and drug delivery. The full potential of bioactive glasses seems still yet to be fulfilled, and many of today’s achievements were unthinkable when research began. As a result, the research involving bioactive glasses is highly stimulating and requires a cross-disciplinary collaboration among glass chemists, bioengineers, and clinicians. The present article provides a picture of the current clinical applications of bioactive glasses, and depicts six relevant challenges deserving to be tackled in the near future. We hope that this work can be useful to both early-stage researchers, who are moving with their first steps in the world of bioactive glasses, and experienced scientists, to stimulate discussion about future research and discover new applications for glass in medicine.

https://www.mdpi.com/2079-4983/9/1/25/pdf

Bioactive Glasses: Where Are We and Where Are We Going?

Enhanced osteoporotic bone regeneration by strontium-substituted calcium silicate bioactive ceramics.

Strontium ranelate is a newly approved drug that can reduce the risk of vertebral fracture, which is attributed to its dual function in increasing the bone formation and decreasing the bone resorption. Strontium-containing hydroxyapatite was also demonstrated to stimulate the osteoblast activity and inhibit the osteoclast activity. However, the molecular mechanisms of strontium underlying such beneficial effects were still not fully understood. In this study, we investigated the effects of strontium on the osteogenic differentiation of human mesenchymal stem cells (MSCs) and its related mechanism; its osteogenic potential was also evaluated using a calvarial defect model in rats. We found that strontium could enhance the osteogenic differentiation of the MSCs, with upregulated extracellular matrix (ECM) gene expression and activated Wnt/β-catenin pathway. After transplanting the collagen-strontium-substituted hydroxyapatite scaffold into the bone defect region, histology and computed tomography scanning revealed that in vivo bone formation was significantly enhanced; the quantity of mature and remodeled bone substantially increased and ECM accumulated. Interestingly, strontium induced an increase of β-catenin expression in newly formed bone area. In this study, we showed for the first time that strontium could stimulate the β-catenin expression in vitro and in vivo, which might contribute to the enhanced osteogenic differentiation of MSCs and in vivo bone formation.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/stem.646

Qixin Zheng

Papers

Strontium Enhances Osteogenic Differentiation of Mesenchymal Stem Cells and In Vivo Bone Formation by Activating Wnt/Catenin Signaling