Biomaterial-assisted local and systemic delivery of bioactive agents for bone repair

Abstract

Although bone tissues possess an intrinsic capacity for repair, there are cases where bone healing is either impaired or insufficient, such as fracture non-union, osteoporosis, osteomyelitis, and cancers. In these cases, treatments like surgical interventions are used, either alone or in combination with bioactive agents, to promote tissue repair and manage associated clinical complications. Improving the efficacy of bioactive agents often requires carriers, with biomaterials being a pivotal player. In this review, we discuss the role of biomaterials in realizing the local and systemic delivery of biomolecules to the bone tissue. The versatility of biomaterials enables design of carriers with the desired loading efficiency, release profile, and on-demand delivery. Besides local administration, systemic administration of drugs is necessary to combat diseases like osteoporosis, warranting bone-targeting drug delivery systems. Thus, chemical moieties with the affinity towards bone extracellular matrix components like apatite minerals have been widely utilized to create bone-targeting carriers with better biodistribution, which cannot be achieved by the drugs alone. Bone-targeting carriers combined with the desired drugs or bioactive agents have been extensively investigated to enhance bone healing while minimizing off-target effects. Herein, these advancements in the field have been systematically reviewed.

Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration

“…Physisorption mainly results in the release of the therapeutic factor through diffusion and leaching with release occurring more rapidly than for chemisorption. An initial burst release of the therapeutic factor is often observed when release happens through diffusion and leaching mechanisms [41]. Drugs that are strongly bound to calcium phosphate particles through chemisorption tend not to exhibit a burst release and therefore demonstrate a slower release rate.…”

“…Tetracycline, however, is known to have an affinity towards divalent metal ions, such as Ca 2+ ions [52]. Various sites within the tetracycline structure including the β-diketone system, the enol groups and the amide group can chelate the Ca 2+ ions [41,52]. Other interactions such as Van der Waals attractions and hydrogen bonding also contribute to the association between tetracycline and calcium phosphate nanoparticles [53].…”

Bone Diseases: Current Approach and Future Perspectives in Drug Delivery Systems for Bone Targeted Therapeutics

“…In the literature, different examples are reported, such as gelatin [134], collagen, hyaluronic acid, PEG, PLGA, CaP, HA, and β-TCP, (and also polyphosphates as additives [135]), but in the case of natural polymers, there are some disadvantages connected to their use, like immunogenicity, rapid degradability, and batch-to-batch variations. On the other hand, synthetic polymers offers the possibility to be easily modified and processed to obtain the suitable properties via the variation of their molecular weights, functional groups and/or structure [136]. Currently, CaPs, and in particular HA and TCP, are widely used in bone tissue engineering as bone substitutes and drug carriers, for their biocompatibility, osteogenic properties and their similarities to bone mineral with which they are able to form strong bonds [137].…”

The Adequacy of Experimental Models and Understanding the Role of Non-coding RNA in Joint Homeostasis and Disease

“…-various 3D-engineered systems based on co-cultures (Owen and Reilly, 2018), -biomimetic materials resembling the natural extracellular environment combined with cells at different stage of maturation (Park et al, 2018), -drug-releasing scaffolds (Zeng et al, 2019), -bioreactors for dynamic culture conditions (Bicho et al, 2018), -organ-on-a chip and integrated microfluidic culture platforms (Dai et al, 2019).…”