Scientists working at the interface between materials science and biomedicine are increasingly interested in developing systems to encourage the regeneration of tissues which have been irreversibly damaged due to disease or injury. To successfully engineer the regrowth of tissue, the controlled and sequential release of multiple small biomolecules into the surrounding tissue is required in order to ensure that cells are stimulated in an appropriate way to form the requisite cellular and extracellular structures.

Now, Ying and colleagues1 describe composite microspheres of a biodegradable copolymer matrix of polylactic - glycolic acid containing inorganic nanoparticles which can offer tunable sequential release of biomolecules, in addition to a tunable lag time in their release for tissue engineering applications.

Fig. 1: Schematic of the process of therapeutic protein delivery from composite microspheres. Copyright AIP

Generally, biodegradable polymer delivery vehicles demonstrate uncontrolled molecular release of their cargoes on degradation through a high initial burst. The researchers overcame this problem by pre-adsorbing biomolecules onto basic calcium phosphate nanoparticles which were distributed into the biodegradable copolymer microspheres. The acidic by-products generated from the degradation of the polymer matrix resulted in the controlled dissolution of the calcium phosphate nanoparticles and subsequent release of the biomolecules (Fig.1).

The scientists controlled calcium phosphate nanoparticle dissolution by adjusting the molecular weights of the polymer matrix—higher molecular weights resulted in slower release of calcium and associated proteins. Release could also be controlled by adjusting the hydrophobicity of the copolymer which slowed down the ingress of water into the microspheres, degradation of the polymers and finally the dissolution of the calcium phosphate nanoparticles.

By careful control of the morphology and chemistry of the microspheres—including the possibility of creating core-shell microspheres to delay molecular release—a variety of release profiles were achieved: most impressively up to a six week delay followed by four weeks of continuous biomolecular release of a model protein. The researchers then demonstrated that the controlled release of bone morphogenetic protein-2 using their microspheres improved the osteogenic activity of embryonic stem cells compared to release from collagen sponges.