This article provides an overview on the application of metallic ions in the fields of regenerative medicine and tissue engineering, focusing on their therapeutic applications and the need to design strategies for controlling the release of loaded ions from biomaterial scaffolds. A detailed summary of relevant metallic ions with potential use in tissue engineering approaches is presented. Remaining challenges in the field and directions for future research efforts with focus on the key variables needed to be taken into account when considering the controlled release of metallic ions in tissue engineering therapeutics are also highlighted.

Bisphosphonates (BPs) are a group of well-established drugs that are applied in the development of metabolic bone disorder-related therapies. There is increasing interest also in the application of BPs in the context of bone tissue engineering, which is the topic of this review, in which an extensive overview of published studies on the development and applications of BPs-based strategies for bone regeneration is provided with special focus on the rationale for the use of different BPs in three-dimensional (3D) bone tissue scaffolds. The different alternatives that are investigated to address the delivery and sustained release of these therapeutic drugs in the nearby tissues are comprehensively discussed, and the most significant published approaches on bisphosphonateconjugated drugs in multifunctional 3D scaffolds as well as the role of BPs within coatings for the improved fixation of orthopedic implants are presented and critically evaluated. Finally, the authors' views regarding the remaining challenges in the fields and directions for future research efforts are highlighted.

One of the major challenges for developing composite scaffolds for BTE is the incorporation of a drug delivery function of sufficient complexity to be able to induce the release patterns that may be necessary for effective osseointegration, vascularization and bone regeneration. Loading 3D scaffolds with different biomolecular agents should produce a codelivery system with different, predetermined release profiles. It is also envisaged that the number of relevant bioactive agents that can be loaded onto scaffolds will be increased, whilst the composite scaffold design should exploit synergistically the different degradation profiles of the organic and inorganic components.

The aim of this work was to develop biodegradable and bioactive materials with sufficient structural integrity and prophylaxis effect against infection based on alginate-bioactive glass composite. The incorporation of bioactive glass nanoparticles (NBG) into Ga-crosslinked alginate films significantly improved their mechanical properties when compared with films fabricated with micron-sized bioactive glass particles. In addition, Ga-alginate films containing NBG induced a bacteriostatic effect in vitro towards S. aureus due to the presence of Ga ions (Ga 3+ ), whose release is controlled solely by crosslinking the ion with alginate. Biomineralization studies in simulated body fluid suggested the deposition of hydroxyapatite on the surface of the films indicating their bioactive nature. In addition, the films were shown to feature biocompatibility toward osteoblast-like cells. Thus, it was shown that Ga-crosslinked composite films possessed relevant physicochemical, biological and controlled bacteriostatic effects which make these materials promising candidates for bone tissue engineering applications.

No abstract