Scaffolds as Structural Tools for Bone-Targeted Drug Delivery

Abstract

Although bone has a high potential to regenerate itself after damage and injury, the efficacious repair of large bone defects resulting from resection, trauma or non-union fractures still requires the implantation of bone grafts. Materials science, in conjunction with biotechnology, can satisfy these needs by developing artificial bones, synthetic substitutes and organ implants. In particular, recent advances in materials science have provided several innovations, underlying the increasing importance of biomaterials in this field. To address the increasing need for improved bone substitutes, tissue engineering seeks to create synthetic, three-dimensional scaffolds made from organic or inorganic materials, incorporating drugs and growth factors, to induce new bone tissue formation. This review emphasizes recent progress in materials science that allows reliable scaffolds to be synthesized for targeted drug delivery in bone regeneration, also with respect to past directions no longer considered promising. A general overview concerning modeling approaches suitable for the discussed systems is also provided.

Keywords: biomaterials; bone; polymer; scaffold; stem cell.

Figure 1

Tissue engineering approach to bone repair: undifferentiated stem cells were seeded within polymeric scaffolds, together with differentiating agents (e.g., dexamethasone) and osteoinductive agents and then implanted in vivo.

Figure 2

(A) Permeation of silatecan camptothecin drug analogue and a protonated 20(S)-4-aminobutyrate substituted prodrug in a hydrated dimyristoylphosphatidylcholine (DMPC) bilayer. Water molecules are represented as silver CPK, bilayer is represented as light blue lines and drugs are shown as VdW spheres. Reproduced with permission from Elsevier [155]. (B) Lipid vesicle containing a mechano-sensitive protein channel simulated with coarse-grain MARTINI force field. Water is represented as blue beads. Reproduced with permission from Royal Society of Chemistry [158]. (C) Binding between G7 PAMAM dendrimer and siRNA fragment; siRNA is represented as dark solid ribbons, while charged primary amine groups are represented as blue/white spheres. Reproduced with permission from Elsevier [150]. (D) Interaction between α-synuclein with 12 nm gold nanoparticle functionalized with partially ionized citrate ligands (charged moieties are shown as red spheres). Reproduced with permission from Wiley [161].