Biological Roles and Delivery Strategies for Ions to Promote Osteogenic Induction

Abstract

Bone is the most studied tissue in the field of tissue regeneration. Even though it has intrinsic capability to regenerate upon injury, several pathologies and injuries could hamper the highly orchestrated bone formation and resorption process. Bone tissue engineering seeks to mimic the extracellular matrix of the tissue and the different biochemical pathways that lead to successful regeneration. For many years, the use of extrinsic factors (i.e., growth factors and drugs) to modulate these biological processes have been the preferred choice in the field. Even though it has been successful in some instances, this approach presents several drawbacks, such as safety-concerns, short release profile and half-time life of the compounds. On the other hand, the use of inorganic ions has attracted significant attention due to their therapeutic effects, stability and lower biological risks. Biomaterials play a key role in such strategies where they serve as a substrate for the incorporation and release of the ions. In this review, the methodologies used to incorporate ions in biomaterials is presented, highlighting the osteogenic properties of such ions and the roles of biomaterials in controlling their release.

Hierarchical Therapeutic Ion‐Based Microspheres with Precise Ratio‐Controlled Delivery as Microscaffolds for In Situ Vascularized Bone Regeneration

“…[ 3 ] Various ions (e.g., Ca, Mg, Si, Sr, Co, Zn, and Cu) have been utilized to direct cell fate or induce specific physiological activities, including vascularization, osteogenic differentiation, neuronal differentiation, and antimicrobial. [ 4 ] Since those ions regulate various biological responses, combining multiple ions to direct the sequential process of vascularized bone regeneration could serve as a promising strategy for tissue engineering. [ 5 ]…”

Evaluation of the immunomodulatory effects of cobalt, copper and magnesium ions in a pro inflammatory environment

“…However, these methods are far from clinical application due to risk for insertional mutagenesis and cytotoxicity as well as long term safety. As an alternative, bioactive ions such as cobalt, copper and magnesium are stable cues which are present at low concentrations in the body and have already shown benefits on tissue regeneration when delivered from scaffolds; however, there are limited evidences showing their immunomodulatory potential 14 .…”

Effect of Artemisinin-Loaded Mesoporous Cerium-Doped Calcium Silicate Nanopowder on Cell Proliferation of Human Periodontal Ligament Fibroblasts

“…Calcium-doped mesoporous materials exhibit improved properties such as a stable mesh structure, high surface area and high bioactivity [ 4 , 5 , 6 ]. Both calcium and silicate ions can promote bone regeneration and increase bone mineral density in vivo [ 7 , 8 , 9 ], while a few studies have unraveled the effectiveness of bioactive mesoporous calcium-silicate nanoparticles on the apical sealing of teeth root canals [ 10 ] and the odontogenic differentiation of human dental pulp stem cells [ 11 ]. Magnesium and strontium doped calcium silicates have shown promising properties as drug carriers or as bone regenerative materials [ 12 , 13 , 14 , 15 ].…”