The polymeric implant material poly(lactide-co-glycolide) (PLGA) degrades by a process of bulk degradation, which allows it to be used for the controlled release of therapeutic molecules from implants and microspheres. The temporal characterization of PLGA microsphere degradation has been limited by the need to destructively monitor the samples at each time point. In this study, a noninvasive imaging technology, optical coherence tomography (OCT), was utilized to characterize the in situ degradation of PLGA microspheres suspended within photo-crosslinked hyaluronic acid (HA) hydrogels. Microspheres with differing degradation rates were loaded with bovine serum albumin (BSA) as a marker protein, and temporal release of protein was correlated with morphological changes observed during 3-D OCT imaging. As proof-of-principle, a microsphere-loaded hydrogel scaffold was implanted in a modified rat calvarial critical size defect model and imaged using OCT. This animal model presents the opportunity to monitor microsphere degradation over time in living animals.

Many molecular imaging techniques rely on tracer methods to visualize specific physiological processes in cells, animals, and humans. A new family of "smart" delivery systems for biomolecules has opened new opportunities for the molecular imaging field. One class of polymeric carriers reversibly become membrane destabilizing in response to sharp pH changes and were designed for delivering proteins and nucleic acids to intracellular compartments. These carriers could enable the use of imaging agents and intracellular reporters whose site of action made them previously inaccessible. A second class of stimuli-responsive polymer-biomolecule conjugates can be reversibly formed into particles of closely defined sizes. The ability to control when and where the protein or DNA species is in the free versus particle form may allow imaging applications that exploit their differential size and diffusion properties.