Assistant Professor Ohio University, United States
Introduction:: Recent work in 3D printing has focused on expanding the polymer library to include newer biomaterials, but there has not been sufficient advancement for pharmacological performance and drug delivery potential, which still make use of the same limited acrylate-containing photopolymers, or utilizes inefficient physical compounding. 1, 2 Pro-drugs, which provide significant advantages for sustainable drug delivery, are excellent candidates for developing such a library of processable materials.
Materials and Methods:: Degradable synthetic polymers (polyesters and polycarabontes)3 and modified salicylic acid derivatives (further including fluorescent dye analogs and pain management agents (lidocaine, prilocaine, etc)) were 3D printed or electrospun into tissue scaffolds and characterized for physical properties. The resultant materials were characterized for resultant physical properties, including their 4D shape changing behavior. Cytocompatibility and antimicrobial testing was performed using both 2D and 3D scaffolding, with subsequent in vivo studies performed using murine subcutaneous tissue models.
Results, Conclusions, and Discussions:: Through a combination of compositional tailoring and processing control, porous material (Figure 1A) loadings greater than 50% could be achieved. The resultant materials display elastomeric behaviors and would be of interest across multiple tissue systems. Release studies confirmed that salicylic acid, as well as drugs and drug analogs, could be synergistically loaded and selectively released across 48 hours to several months. 3D cytocompatibility studies using adipocytes (Figure 1B) and fibroblasts (1C-D) demonstrated cellular proliferation over 14 days, while in vivo data demonstrates the biocompatibility of such materials in subcutaneous murine models Polyactive tissue scaffolds were produced using both electrospinning and 3D printing by exploiting modified salicylic acids capable of reactive processing. These scaffolds undergo hydrolytic surface erosion to release both the pro-drug salicylic acid. Importantly, this material system is compatible with loading of other drugs for sequential, linear release profiles as a function composition, allowing for additional erosion control without compromising cytocompatibility, representing a distinct advance for 3D printing of pharmaceuticals.
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References (Optional): : Goyanes, A.; Det-Amornrat, U.; Wang, J.; Basit, A. W.; Gaisford, S., 3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems. J Control Release 2016, 234, 41-8.
2. Wang, J.; Goyanes, A.; Gaisford, S.; Basit, A. W., Stereolithographic (SLA) 3D printing of oral modified-release dosage forms. Int. J. Pharm. 2016, 503, (1-2), 207-12.
3. Weems, A. C. A., M.C.A.; Huckstepp, R.T.R.; Dove, A.P., 4D Polycarbonates via Stereolithography as Scaffolds for Soft Tissue Repair Nat. Commun. 2021.