Geometric Mismatch Promotes Anatomic Repair in Periorbital Bony Defects in Skeletally Mature Yucatan Minipigs.

Porous tissue-engineered 3D-printed scaffolds are a compelling alternative to autografts for the treatment of large periorbital bone defects. Matching the defect-specific geometry has long been considered an optimal strategy to restore pre-injury anatomy. However, studies in large animal models have revealed that biomaterial-induced bone formation largely occurs around the scaffold periphery. Such ectopic bone formation in the periorbital region can affect vision and cause disfigurement. To enhance anatomic reconstruction, geometric mismatches are introduced in the scaffolds used to treat full thickness zygomatic defects created bilaterally in adult Yucatan minipigs. 3D-printed, anatomically-mirrored scaffolds are used in combination with autologous stromal vascular fraction of cells (SVF) for treatment. An advanced image-registration workflow is developed to quantify the post-surgical geometric mismatch and correlate it with the spatial pattern of the regenerating bone. Osteoconductive bone growth on the dorsal and ventral aspect of the defect enhances scaffold integration with the native bone while medio-lateral bone growth leads to failure of the scaffolds to integrate. A strong positive correlation is found between geometric mismatch and orthotopic bone deposition at the defect site. The data suggest that strategic mismatch >20% could improve bone scaffold design to promote enhanced regeneration, osseointegration, and long-term scaffold survivability.

Design of cell-type-specific hyperstable IL-4 mimetics via modular de novo scaffolds.

The interleukin-4 (IL-4) cytokine plays a critical role in modulating immune homeostasis. Although there is great interest in harnessing this cytokine as a therapeutic in natural or engineered formats, the clinical potential of native IL-4 is limited by its instability and pleiotropic actions. Here, we design IL-4 cytokine mimetics (denoted Neo-4) based on a de novo engineered IL-2 mimetic scaffold and demonstrate that these cytokines can recapitulate physiological functions of IL-4 in cellular and animal models. In contrast with natural IL-4, Neo-4 is hyperstable and signals exclusively through the type I IL-4 receptor complex, providing previously inaccessible insights into differential IL-4 signaling through type I versus type II receptors. Because of their hyperstability, our computationally designed mimetics can directly incorporate into sophisticated biomaterials that require heat processing, such as three-dimensional-printed scaffolds. Neo-4 should be broadly useful for interrogating IL-4 biology, and the design workflow will inform targeted cytokine therapeutic development.

A biodegradable 3D woven magnesium-based scaffold for orthopedic implants.

Porous Magnesium (Mg) is a promising biodegradable scaffold for treating critical-size bone defects, and as an essential element for human metabolism, Mg has shown sufficient biocompatibility. Its elastic moduli and yield strengths are closer to those of cortical bone than common, inert metallic implants, effectively reducing stress concentrations around host tissue as well as stress shielding. More importantly, Mg can degrade and be absorbed in the human body in a safe and controlled manner, thereby reducing the need for second surgeries to remove implants. The development of porous Mg scaffolds via conventional selective laser melting techniques has been limited due to Mg's low boiling point, high vapor pressures, high reactivity, and non-ideal microstructures in additively manufactured parts. Here we present an exciting alternative to conventional additive techniques: 3D weaving with Mg wires that have controlled chemistries and microstructures. The weaving process offers high throughput manufacturing as well as porous architectures that can be optimized for stiffness and porosity with topology optimization. Once woven, we dip-coat the weaves with polylactic acid to enhance their strength and corrosion resistance. Following fabrication, we characterize their mechanical properties, corrosion behavior, and cell compatibilityin vitro, and we use an intramuscular implantation model to evaluate theirin vivocorrosion behavior and tissue response.

A robust, autonomous, volumetric quality assurance method for 3D printed porous scaffolds.

Bone tissue engineering strategies aimed at treating critical-sized craniofacial defects often utilize novel biomaterials and scaffolding. Rapid manufacturing of defect-matching geometries using 3D-printing strategies is a promising strategy to treat craniofacial bone loss to improve aesthetic and regenerative outcomes. To validate manufacturing quality, a robust, three-dimensional quality assurance pipeline is needed to provide an objective, quantitative metric of print quality if porous scaffolds are to be translated from laboratory to clinical settings. Previously published methods of assessing scaffold print quality utilized one- and two-dimensional measurements (e.g., strut widths, pore widths, and pore area) or, in some cases, the print quality of a single phantom is assumed to be representative of the quality of all subsequent prints. More robust volume correlation between anatomic shapes has been accomplished; however, it requires manual user correction in challenging cases such as porous objects like bone scaffolds. Here, we designed porous, anatomically-shaped scaffolds with homogenous or heterogenous porous structures. We 3D-printed the designs with acrylonitrile butadiene styrene (ABS) and used cone-beam computed tomography (CBCT) to obtain 3D image reconstructions. We applied the iterative closest point algorithm to superimpose the computational scaffold designs with the CBCT images to obtain a 3D volumetric overlap. In order to avoid false convergences while using an autonomous workflow for volumetric correlation, we developed an independent iterative closest point (I-ICP10) algorithm using MATLAB®, which applied ten initial conditions for the spatial orientation of the CBCT images relative to the original design. Following successful correlation, scaffold quality can be quantified and visualized on a sub-voxel scale for any part of the volume.

Fabrication of High Surface Area Microporous ZnO from ZnO/Carbon Sacrificial Composite Monolith Template.

Fabrication of porous materials from the standard sacrificial template method allows metal oxide nanostructures to be produced and have several applications in energy, filtration and constructing sensing devices. However, the low surface area of these nanostructures is a significant drawback for most applications. Here, we report the synthesis of ZnO/carbon composite monoliths in which carbon is used as a sacrificial template to produce zinc oxide (ZnO) porous nanostructures with a high specific surface area. The synthesized porous oxides of ZnO with a specific surface area of 78 m2/g are at least one order of magnitude higher than that of the ZnO nanotubes reported in the literature. The crucial point to achieving this remarkable result was the usage of a novel ZnO/carbon template where the carbon template was removed by simple heating in the air. As a high surface area porous nanostructured ZnO, these synthesized materials can be useful in various applications including catalysis, photocatalysis, separation, sensing, solar energy harvest and Zn-ion battery and as supercapacitors for energy storage.

Point-of-care treatment of geometrically complex midfacial critical-sized bone defects with 3D-Printed scaffolds and autologous stromal vascular fraction.

Critical-sized midfacial bone defects present a unique clinical challenge due to their complex three-dimensional shapes and intimate associations with sensory organs. To address this challenge, a point-of-care treatment strategy for functional, long-term regeneration of 2 cm full-thickness segmental defects in the zygomatic arches of Yucatan minipigs is evaluated. A digital workflow is used to 3D-print anatomically precise, porous, biodegradable scaffolds from clinical-grade poly-ε-caprolactone and decellularized bone composites. The autologous stromal vascular fraction of cells (SVF) is isolated from adipose tissue extracts and infused into the scaffolds that are implanted into the zygomatic ostectomies. Bone regeneration is assessed up to 52 weeks post-operatively in acellular (AC) and SVF groups (BV/DV = 0.64 ± 0.10 and 0.65 ± 0.10 respectively). In both treated groups, bone grows from the adjacent tissues and restores the native anatomy. Significantly higher torque is required to fracture the bone-scaffold interface in the SVF (7.11 ± 2.31 N m) compared to AC groups (2.83 ± 0.23 N m). Three-dimensional microcomputed tomography analysis reveals two distinct regenerative patterns: osteoconduction along the periphery of scaffolds to form dense lamellar bone and small islands of woven bone deposits growing along the struts in the scaffold interior. Overall, this study validates the efficacy of using 3D-printed bioactive scaffolds with autologous SVF to restore geometrically complex midfacial bone defects of clinically relevant sizes while also highlighting remaining challenges to be addressed prior to clinical translation.

ZnO Nanoparticle Fortified Highly Permeable Carbon/Silica Monoliths as a Flow-Through Media.

We demonstrate a facile one-pot synthesis of porous "flow-through" ZnO nanoparticle impregnated carbon/silica monoliths with high mechanical strength and interconnected end-to-end pores decorated with functional and catalytic nanoparticles. The materials and conditions for the synthesis were tailored to achieve the desired properties of high mechanical strength, good flow-through permeability, and crack-free morphology. Monoliths were prepared from a resorcinol formaldehyde rout but with the addition of tetraethyl-orthosilicate and a metal oxide precursor, ZnCl2. The monoliths were ambient dried and carbonized under optimized conditions to suppress cracks. Compressive tests of both the resin and carbonized monoliths were performed to examine the effect of the metal oxide precursor on the mechanical properties. The permeability of the monoliths was determined to verify their utility as a flow-through material. The monoliths exhibited a high compressive modulus of ∼30 MPa compared with conventional carbon aerogels and a permeability of ∼10-12 m2. Various characterization techniques were used to analyze the surface morphology, pore texture, and chemical composition of the monoliths. Finally, Ag nanoparticles were incorporated in the monoliths to demonstrate an example of a "flow-through" catalysis application where controlled catalytic conversion of para-nitrophenol into para-aminophenol could be achieved in a continuous flow reactor mode.