3D printed dual macro-, microscale porous network as a tissue engineering scaffold with drug delivering function

Abstract

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.

Design and Fabrication of Three-Dimensional Printed Scaffolds for Cancer Precision Medicine

“…The fibrous matrices have also been widely used in many biomedical applications, including tissue engineering and drug delivery. [15][16][17][18] The fibrillar scaffolds exhibit large area to volume ratio and porosity, which are advantageous for effective drug delivery. Moreover, these implants facilitate the implantability into the tumor bed after surgical removal due to their flexible conformation and eventually support tissue infiltration and regeneration in the implantation sites.…”

“…However, a major drawback of FDM products as DDS is that the printing process requires prepreparation of printable filament, and the drugs are often incorporated on the surface of the scaffolds after printing, impregnation method, resulting in a low loading percentage with a burst release. 18,36 Therefore, the hot-melt extrusion method has been used to molecularly disperse the drug throughout the polymer matrix, but high processing temperatures can lead to significant degradation of drugs. Therefore, future studies are needed to develop strategies to incorporate a large amount of drugs on FDM products.…”

Local Doxorubicin Delivery via 3D‐Printed Porous Scaffolds Reduces Systemic Cytotoxicity and Breast Cancer Recurrence in Mice

“…[21,33] Recently, our group devised a manufacturing technique that allows us to create microscale pores inside the struts of conventional macroscale porous scaffolds made by melt extrusion. [34] These bimodal scaffolds are manufactured by combining melt extrusion additive manufacturing with salt leaching. Using PCL as a model polymer and simply mixing it with a microsized phosphate salt particle as a porogen before extrusion, we could manufacture scaffolds with designed macroscale architecture that contain microscale pores of controlled size after salt leaching.…”

“…Importantly, the microscale porous networks in these scaffolds were shown to facilitate immobilization of antibiotics (including vancomycin and gentamicin) and chemotherapeutic drugs (including DOX and paclitaxel) by simple soak-loading. [35] The loaded scaffolds were also shown to reduce the burst release of the drugs and thus extended their elution profiles through the effects of the microscale pores and the scaffold's surface chemistry. [35] However, it is still unknown how the drug-loaded scaffolds would perform in vivo.…”

“…[35] The loaded scaffolds were also shown to reduce the burst release of the drugs and thus extended their elution profiles through the effects of the microscale pores and the scaffold's surface chemistry. [35] However, it is still unknown how the drug-loaded scaffolds would perform in vivo.…”