Evolution of implants and advancements for osseointegration: A narrative review.

Since ancient times, reduction and internal fixation has been applied to restore skeletal integrity. Despite advances in the understanding of fracture healing, the risk of complication such as implant loosening or implant-related infection still depicts a challenging complication. Nowadays, a great deal of research is devoted to unreveal the impact of implant surface modifications on osteogenic processes to enhance bone consolidation and osseointegration. This narrative review is aimed to (1) show the evolution and already achieved milestones of implant optimization, and (2) to outline the key factors that contribute to an enhanced osseointegration. Different physical and chemical roughening techniques are currently applied in various studies. Surface patterning on the nanoscale has been found to be an essential factor for the biological response, achievable by e.g. anodisation or laser texturing. Besides surface roughening, also different coating methods are vastly investigated. Next to metal or inorganic compounds as coating material, a variety of biomolecules is currently studied for their osteosupportive capacities. Osseointegration can be improved by surface modification on the micro and nanoscale. Bioactive agents can further improve the osseointegration potential. Used agents at the moment are e.g. inorganic compounds, growth factors (BMPs and non-BMPs) and antiresorptive drugs. The advancement in research on new implant generations therefore aims at actively supporting osseointegration processing.

Implant-bone-interface: Reviewing the impact of titanium surface modifications on osteogenic processes in vitro and in vivo.

Titanium is commonly and successfully used in dental and orthopedic implants. However, patients still have to face the risk of implant failure due to various reasons, such as implant loosening or infection. The risk of implant loosening can be countered by optimizing the osteointegration capacity of implant materials. Implant surface modifications for structuring, roughening and biological activation in favor for osteogenic differentiation have been vastly studied. A key factor for a successful stable long-term integration is the initial cellular response to the implant material. Hence, cell-material interactions, which are dependent on the surface parameters, need to be considered in the implant design. Therefore, this review starts with an introduction to the basics of cell-material interactions as well as common surface modification techniques. Afterwards, recent research on the impact of osteogenic processes in vitro and vivo provoked by various surface modifications is reviewed and discussed, in order to give an update on currently applied and developing implant modification techniques for enhancing osteointegration.

miR-128a Acts as a Regulator in Cardiac Development by Modulating Differentiation of Cardiac Progenitor Cell Populations.

MicroRNAs (miRs) appear to be major, yet poorly understood players in regulatory networks guiding cardiogenesis. We sought to identify miRs with unknown functions during cardiogenesis analyzing the miR-profile of multipotent Nkx2.5 enhancer cardiac progenitor cells (NkxCE-CPCs). Besides well-known candidates such as miR-1, we found about 40 miRs that were highly enriched in NkxCE-CPCs, four of which were chosen for further analysis. Knockdown in zebrafish revealed that only miR-128a affected cardiac development and function robustly. For a detailed analysis, loss-of-function and gain-of-function experiments were performed during in vitro differentiations of transgenic murine pluripotent stem cells. MiR-128a knockdown (1) increased Isl1, Sfrp5, and Hcn4 (cardiac transcription factors) but reduced Irx4 at the onset of cardiogenesis, (2) upregulated Isl1-positive CPCs, whereas NkxCE-positive CPCs were downregulated, and (3) increased the expression of the ventricular cardiomyocyte marker Myl2 accompanied by a reduced beating frequency of early cardiomyocytes. Overexpression of miR-128a (4) diminished the expression of Isl1, Sfrp5, Nkx2.5, and Mef2c, but increased Irx4, (5) enhanced NkxCE-positive CPCs, and (6) favored nodal-like cardiomyocytes (Tnnt2+, Myh6+, Shox2+) accompanied by increased beating frequencies. In summary, we demonstrated that miR-128a plays a so-far unknown role in early heart development by affecting the timing of CPC differentiation into various cardiomyocyte subtypes.

Recent advances and future perspectives of sol-gel derived porous bioactive glasses: a review.

The sol-gel derived porous bioactive glasses have drawn worldwide attention by virtue of the convenience and flexibility of this versatile synthesis method. In this review, the recent advances in sol-gel processed porous bioactive glasses in biomedical fields, especially for bone tissue regeneration applications have been comprehensively reviewed. Generally, it is envisaged that the morphology and chemical compositions of sol-gel derived porous bioactive glasses significantly affect their biological properties. Therefore, the controlled synthesis of these porous glasses is critical to their effective use in the biomedical fields. With this context, the first part of the review briefly describes the fundamentals of the sol-gel technique. In the subsequent section, different approaches frequently used for the sol-gel synthesis of porous glasses such as microemulsion and acid-catalyzed based synthesis have been reviewed. In the later part of the review, different types of sol-gel derived bioactive glasses namely silica, phosphate and silica-titania based glasses along with organic-inorganic hybrids materials have been discussed. The review also discusses the chemical, surface, mechanical and biological properties and further highlights the strategies to control the pore structure, shape, size and compositions of sol-gel derived bioactive glasses. Finally, the review provides a detailed discussion about the bone tissue regeneration application of different types of sol-gel derived bioactive glasses and presents future research perspectives.