In this work, we present a printing method to fabricate scaffolds consisting of multimaterial segmented fibers. Particularly, we developed a reproducible printing process to create single fibers with multiple discrete compositions and control over the distribution of particulate ceramics-namely hydroxyapatite (HA) and btricalcium phosphate (TCP)-within poly(e-caprolactone)-based composite scaffolds. Tensile testing revealed that the mechanical integrity of individual segmented fibers was preserved compared with nonsegmented fibers, and microcomputed tomography and thermal analysis confirmed the homogeneous distribution of ceramics incorporated in the fiber compositions. Moreover, we printed and characterized composite scaffolds containing model inverse radial gradients of HA and TCP that could serve as a tunable platform to control the degradation rate of the scaffolds and match bone tissue ingrowth. The morphology of the gradient scaffolds was assessed, and their bulk compressive mechanical properties were found to be in the same range as human trabecular bone. Finally, scaffold degradation was monitored for up to 10 weeks in phosphate-buffered saline pH 7.4 and 0.1 M HCl solution, and scaffolds containing TCP in their composition showed increased degradation compared with those containing HA. This work provides a new methodology for the fabrication and characterization of porous scaffolds containing designer composition gradients that could serve as a platform for the preparation of complex scaffolds for tissue engineering applications.

This work investigated a new three-dimensional (3D) printing methodology to prepare porous scaffolds containing horizontal pore and composition gradients. To achieve that, a multimaterial printing technology developed in our laboratory was adapted to incorporate pore gradients. Fibers were printed by welding segments with unique material compositions and fiber diameters. Particularly, we focused on the preparation of model composite poly(e-caprolactone)-based scaffolds with radial gradients of particulate hydroxyapatite (HA) content (higher concentrations in the outer region of the scaffold) and porosity (higher in the inner region). The morphology of the scaffolds revealed that the methodology allowed the fabrication of discrete regions with compressive mechanical properties similar to human trabecular bone while maintaining structural integrity. HA distribution was homogeneous within individual regions and no particle aggregation was detected by microCT analysis and Alizarin Red S staining. Finally, the incubation of the scaffolds in simulated body fluid resulted in the deposition of significantly higher amounts of calcium deposits in the regions of the scaffolds with higher HA content. This work provides a new tool for the preparation of porous scaffolds containing porosity and composition gradients for complex tissue engineering applications.

Cutaneous fungal infection is a challenging condition to treat that primarily afflicts immunocompromised patients. Local antifungal therapy may permit the delivery of high concentrations of antifungals directly to wounds while minimizing systemic toxicities. However, the field currently lacks suitable in vivo models. Therefore, a large cutaneous wound was created in immunosuppressed mice and inoculated with Aspergillus fumigatus. We fabricated biodegradable polymer microparticles (MPs) that were capable of locally delivering antifungal and characterized in vitro release kinetics. We compared wound bed size, fungal burden, and histological presence of fungi in mice treated with antifungal‐loaded MPs. Mice with a cutaneous defect but no infection, mice with infected cutaneous defect but no treatment, and infected mice treated with blank MPs were used as controls. Infection of large wounds inhibited healing and resulted in tissue invasion in an inoculum‐dependent manner. MPs were capable of releasing antifungals at concentrations above A. fumigatus Minimum Inhibitory Concentration (MIC) for at least 6 days. Wounds treated with MPs had significantly decreased size compared with no treatment (64.2% vs. 19.4% wound reduction, p = 0.002) and were not significantly different from uninfected controls (64.2% vs. 58.1%, p = 0.497). This murine model may serve to better understand cutaneous fungal infection and evaluate local biomaterials‐based therapies. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1867–1874, 2019.