In the past thirty years, a number of biomaterials have shown the ability to induce bone formation when implanted at heterotopic sites, an ability known as osteoinduction. Such biomaterials -osteoinductive biomaterials -hold great potential for the development of new therapies in bone regeneration. Although a variety of well characterised osteoinductive biomaterials have so far been reported in the literature, scientists still lack fundamental understanding of the biological mechanism underlying the phenomenon by which they induce bone formation. This is further complicated by the observations that larger animal models are required for research, since limited, if any, bone induction by biomaterials is observed in smaller animals, including particularly rodents. Besides interspecies variation, variations among individuals of the same species have been observed. Furthermore, comparing different studies and drawing general conclusions is challenging, as these usually differ not only in the physico-chemical and structural properties of the biomaterials, but also in animal model, implantation site and duration of the study. Despite these limitations, the knowledge of material properties relevant for osteoinduction to occur has tremendously increased in the past decades. Here we review the properties of osteoinductive biomaterials, in the light of the model and the conditions under which they were tested. Furthermore, we give an insight into the biological processes governing osteoinduction by biomaterials and our view on the future perspectives in this research fi eld.

The blastocyst (the early mammalian embryo) forms all embryonic and extra-embryonic tissues, including the placenta. It consists of a spherical thin-walled layer, known as the trophectoderm, that surrounds a fluid-filled cavity sheltering the embryonic cells . From mouse blastocysts, it is possible to derive both trophoblast and embryonic stem-cell lines , which are in vitro analogues of the trophectoderm and embryonic compartments, respectively. Here we report that trophoblast and embryonic stem cells cooperate in vitro to form structures that morphologically and transcriptionally resemble embryonic day 3.5 blastocysts, termed blastoids. Like blastocysts, blastoids form from inductive signals that originate from the inner embryonic cells and drive the development of the outer trophectoderm. The nature and function of these signals have been largely unexplored. Genetically and physically uncoupling the embryonic and trophectoderm compartments, along with single-cell transcriptomics, reveals the extensive inventory of embryonic inductions. We specifically show that the embryonic cells maintain trophoblast proliferation and self-renewal, while fine-tuning trophoblast epithelial morphogenesis in part via a BMP4/Nodal-KLF6 axis. Although blastoids do not support the development of bona fide embryos, we demonstrate that embryonic inductions are crucial to form a trophectoderm state that robustly implants and triggers decidualization in utero. Thus, at this stage, the nascent embryo fuels trophectoderm development and implantation.

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The combination of the high mechanical strength of metals with the osteoconductive properties of calcium phosphates make hydroxyapatite coatings on titanium implants widely used in orthopedic surgery. However, the most popular coating method, plasma spraying, exhibits some important drawbacks: the inability to cover porous implants and to incorporate biologically active agents, delamination, and particle release. The aim of this study was to elaborate a dense, strong, and thick calcium-phosphate coating on titanium and poroustantalum implants using a two-step biomimetic procedure. In the first step, the implants were soaked in a solution that was 5 times more concentrated than regular simulated body fluid (SBF-A solution). A thin but uniform amorphous calciumphosphate coating was deposited on the metal. Then, the implants were immersed in the SBF-B solution, which had a similar composition as the SBF-A solution, but with decreased contents of crystal growth inhibitors (i.e., Mg 2؉ and HCO 3 ؊ ). This resulted in the fast precipitation of a 30 m thick crystalline calcium-phosphate coating. The pH of the SBF-B solution and the thickness of the crystalline coating layer were studied as a function of time. The Fourier transform infrared spectra and X-ray diffraction patterns showed that this new coating closely resembles bone mineral. Our biomimetic coating should facilitate rapid bone formation around the implant, reducing therewith the patient's recovery time after surgery.