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 μg/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.

Tissue engineering macroporous scaffolds are important for regeneration of large volume defects resulting from diseases such as breast or bone cancers. Another important part of the treatment of these conditions is adjuvant drug therapy to prevent disease recurrence or surgical site infection. In this study, we developed a new type of macroporous scaffolds that have drug loading and release functionality to use in these scenarios. 3D printing allows for building macroporous scaffolds with deterministically designed complex architectures for tissue engineering yet they often have low surface areas thus limiting their drug loading capability. In this proof-of-concept study, we aimed to introduce microscale porosity into macroporous scaffolds to allow for efficient yet simple soak-loading of various clinical drugs and control their release. Manufacturing of scaffolds having both macroporosity and microscale porosity remains a difficult task. Here, we combined porogen leaching and 3D printing to achieve this goal. Porogen microparticles were mixed with medical grade polycaprolactone and extruded into scaffolds having macropores of 0.7 mm in size. After leaching, intra-strut microscale pores were realized with pore size of 20–70 μm and a total microscale porosity of nearly 40%. Doxorubicin (DOX), paclitaxel (PTX) and cefazolin (CEF) were chosen as model drugs of different charges and solubilities to soak-load the scaffolds and achieved loading efficiency of over 80%. The microscale porosity was found to significantly reduce the burst release allowing the microporous scaffolds to release drugs up to 200, 500 and 150 h for DOX, PTX and CEF, respectively. Finally, cell assays were used and confirmed the bioactivities and dose response of the drug-loaded scaffolds. Together, the findings from this proof-of-concept study demonstrate a new type of scaffolds with dual micro-, macro-porosity for tissue engineering applications with intrinsic capability for efficient loading and sustained release of drugs to prevent post-surgery complications.

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The concept of using macroscale porous scaffolds as local drug reservoirs to prevent cancer recurrence has received little attention. To extend the use of these scaffolds as drug delivery devices, the morphology needs to be optimized. Here, a porous scaffold that can work as efficient drug reservoirs is developed. A combination of additive manufacturing and salt leaching techniques to produce scaffolds of medical grade poly(ε‐caprolactone) that has macroscale pores of 300–500 µm and intrastrut microscale pores of 5–35 µm in size is used. The chemotherapeutic drug, doxorubicin (DOX), is loaded onto the porous scaffolds by soaking with the loading efficacy as high as 90%. The DOX‐loaded scaffolds display a biphasic monotonic drug release up to 28 d, and a dose‐dependent chemotherapeutic effect against breast cancer cells, MDA‐MB‐231. Compared to one‐time intravenous injection of 40 µg DOX, implantation of scaffolds containing only 2 or 8 µg of DOX after tumor removal in mice shows lower cardio‐cytotoxicity, reduced local cancer recurrence, and is correlated with a lower metastasis progression in lungs, liver, and spleen in 28 d of treatment. These bimodal scaffolds are thus promising in the development of scaffolds in breast cancer after tumor removal.