3D printed Polycaprolactone scaffolds with dual macro-microporosity for applications in local delivery of antibiotics

Advanced scaffolds used in tissue regenerating applications should be designed to address clinically relevant complications such as surgical site infection associated with surgical procedures. Recognizing that patient specific scaffolds with local drug delivery capabilities are a promising approach, we combined 3D printing with traditional salt-leaching techniques to prepare a new type of scaffold with purposely designed macro- and micro porosity. The dual macro/micro porous scaffolds of medical-grade polycaprolactone (mPCL) were characterized for their porosity, surface area, mechanical properties and degradation. The use of these scaffolds for local prophylactic release of Cefazolin to inhibit S. aureus growth was investigated as an example of drug delivery with this versatile platform. The introduction of microporosity and increased surface area allowed for loading of the scaffold using a simple drop-loading method of this heat-labile antibiotic and resulted in significant improvement in its release for up to 3 days. The Cefazolin released from scaffolds retained its bioactivity similar to that of fresh Cefazolin. There were no cytotoxic effects in vitro against 3 T3 fibroblasts at Cefazolin concentration of up to 100 mu g/ml and no apparent effects on blood clot formation on the scaffolds in vitro. This study therefore presents a novel type of scaffolds with dual macro- and micro-porosity manufactured by a versatile method of 3D printing combined with salt-leaching. These scaffolds could be useful in tissue regeneration applications where it is desirable to prevent complications using local delivery of drugs.