This review brings up to date the state of the art of strontium and zinc based regenerative therapies, both having a promoting effect on tissue formation and a role inhibiting resorption in musculoskeletal disorders.

A novel series of mono and bisnaphthalimides was synthesized and their antiproliferative activities were evaluated against three tumor cell lines. Bisnaphthalimides 3 and 4, bearing a pyrazine ring fused to the naphthalimide system, showed activities in the order of 10⁻⁸ µM, similar to elinafide. DNA binding properties and the ability to induce DNA damage were studied for some of the most active compounds.

Regenerative therapies based on tissue engineering are becoming the most promising alternative for the treatment of osteoarthritis and rheumatoid arthritis. However, regeneration of full-thickness articular osteochondral defects that reproduces the complexity of native cartilage and osteochondral interface still remains challenging. Hence, in this work, we present the fabrication, physic-chemical characterization, and in vitro and in vivo evaluation of biomimetic hierarchical scaffolds that mimic both the spatial organization and composition of cartilage and the osteochondral interface. The scaffold is composed of a composite porous support obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the presence of biodegradable poly(D,L-lactide-co-glycolide) (PLGA), bioactive tricalcium phosphate β-TCP and the bone promoting strontium folate (SrFO), with a gradient biomimetic photo-polymerized methacrylated hyaluronic acid (HAMA) based hydrogel containing the bioactive zinc folic acid derivative (ZnFO). Microscopical analysis of hierarchical scaffolds showed an open interconnected porous open microstructure and the in vitro behaviour results indicated high swelling capacity with a sustained degradation rate. In vitro release studies during 3 weeks indicated the sustained leaching of bioactive compounds, i.e., Sr²⁺, Zn²⁺ and folic acid, within a biologically active range without negative effects on human osteoblast cells (hOBs) and human articular cartilage cells (hACs) cultures. In vitro co-cultures of hOBs and hACs revealed guided cell colonization and proliferation according to the matrix microstructure and composition. In vivo rabbit-condyle experiments in a critical-sized defect model showed the ability of the biomimetic scaffold to promote the regeneration of cartilage-like tissue over the scaffold and neoformation of osteochondral tissue.

B-vitamins are a group of soluble vitamins which are cofactors of some of the enzymes involved in the metabolic pathways of carbohydrates, fats and proteins. These compounds participate in a number of functions as cardiovascular, brain or nervous systems. Folic acid is described as an accessible and multifunctional niche component that can be used safely, even combined with other compounds, which gives it high versatility. Also, due to its non-toxicity and great stability, folic acid has attracted much attention from researchers in the biomedical and bioengineering area, with an increasing number of works directed at using folic acid and its derivatives in tissue engineering therapies as well as regenerative medicine. Thus, this review provides an updated discussion about the most relevant advances achieved during the last five years, where folic acid and other vitamins B have been used as key bioactive compounds for enhancing the effectiveness of biomaterials’ performance and biological functions for the regeneration of tissues and organs.