Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds

Abstract

This paper provides an extensive overview of published studies on the development and applications of three-dimensional bone tissue engineering (TE) scaffolds with potential capability for the controlled delivery of therapeutic drugs. Typical drugs considered include gentamicin and other antibiotics generally used to combat osteomyelitis, as well as anti-inflammatory drugs and bisphosphonates, but delivery of growth factors is not covered in this review. In each case reviewed, special attention has been given to the technology used for controlling the release of the loaded drugs. The possibility of designing multifunctional three-dimensional bone TE scaffolds for the emerging field of bone TE therapeutics is discussed. A detailed summary of drugs included in three-dimensional scaffolds and the several approaches developed to combine bioceramics with various polymeric biomaterials in composites for drug-delivery systems is included. The main results presented in the literature are discussed and the remaining challenges in the field are summarized with suggestions for future research directions.

Figure 1.

Scanning electron microscopy images showing typical pore structures of scaffolds successfully developed for bone TE: (a) bioactive glass–ceramic scaffolds fabricated by the foam replica method (Chen, Q. Z. et al. 2006); (b) PDLLA foam fabricated by thermally induced phase separation (Maquet & Jerome 1997); (c) polymer scaffold architectures developed by FDM (Hutmacher 2000). (Part (c) reproduced from Hutmacher (2000) with permission of Elsevier.)

Figure 2.

Schematic representation of the most common strategies to deliver drugs from three-dimensional scaffolds in bone TE. Drugs may be adsorbed onto the pore surface of the scaffolds in either their unprotected (a) or their protected (microsphere/matrix) (b) forms. Alternatively, drugs may be entrapped in the scaffold structure in either their unprotected (c) or their protected (microsphere/matrix) (d) forms.