Comprehensive feasibility evaluation of small-diameter 3D templated vascular graft via physical characterizations andin-vivoexperiments.

3D printing (3DP) technology for tissue engineering applications has been extensively studied for materials and processes. However, clinical application to the vascular system was limited owing to mechanical inconsistency and toxicity. Here, we characterized 3D templated artificial vascular grafts (3D grafts), which were fabricated by an integrative method involving 3DP, dip coating, and salt leaching method. The as-fabricated grafts were featured with micrometer-scale porosity enabling tissue-mimetic mechanical softness comparable with native blood vessels. In terms of mechanical properties and water permeability, the fabricated 3D grafts exhibited comparable or superior performances compared to the commercialized grafts. Furthermore, thein-vivostability of the 3D graft was validated through a toxicity test, and the small-diameter 3D graft was transplanted into a rat to confirm the implant's performance. Overall, the experimental results demonstrated the clinical feasibility of the 3D graft with retaining the mechanical biocompatibility and also revealed the possibility of patient-specific customization.

Nanoscale geometry determines mechanical biocompatibility of vertically aligned nanofibers.

Vertically aligned carbon nanofibers (VACNFs) are promising material candidates for neural biosensors due to their ability to detect neurotransmitters in physiological concentrations. However, the expected high rigidity of CNFs could induce mechanical mismatch with the brain tissue, eliciting formation of a glial scar around the electrode and thus loss of functionality. We have evaluated mechanical biocompatibility of VACNFs by growing nickel-catalyzed carbon nanofibers of different lengths and inter-fiber distances. Long nanofibers with large inter-fiber distance prevented maturation of focal adhesions, thus constraining cells from obtaining a highly spread morphology that is observed when astrocytes are being contacted with stiff materials commonly used in neural implants. A silicon nanopillar array with 500 nm inter-pillar distance was used to reveal that this inhibition of focal adhesion maturation occurs due to the surface nanoscale geometry, more precisely the inter-fiber distance. Live cell atomic force microscopy was used to confirm astrocytes being significantly softer on the long Ni-CNFs compared to other surfaces, including a soft gelatin hydrogel. We also observed hippocampal neurons to mature and form synaptic contacts when being cultured on both long and short carbon nanofibers, without having to use any adhesive proteins or a glial monoculture, indicating high cytocompatibility of the material also with neuronal population. In contrast, neurons cultured on a planar tetrahedral amorphous carbon sample showed immature neurites and indications of early-stage apoptosis. Our results demonstrate that mechanical biocompatibility of biomaterials is greatly affected by their nanoscale surface geometry, which provides means for controlling how the materials and their mechanical properties are perceived by the cells. STATEMENT OF SIGNIFICANCE: Our research article shows, how nanoscale surface geometry determines mechanical biocompatibility of apparently stiff materials. Specifically, astrocytes were prevented from obtaining highly spread morphology when their adhesion site maturation was inhibited, showing similar morphology on nominally stiff vertically aligned carbon fiber (VACNF) substrates as when being cultured on ultrasoft surfaces. Furthermore, hippocampal neurons matured well and formed synapses on these carbon nanofibers, indicating high biocompatibility of the materials. Interestingly, the same VACNF materials that were used in this study have earlier also been proven to be capable for electrophysiological recordings and sensing neurotransmitters at physiological concentrations with ultra-high sensitivity and selectivity, thus providing a platform for future neural probes or smart culturing surfaces with superior sensing performance and biocompatibility.

Soft Biomimetic 3D Free-Form Artificial Vascular Graft Using a Highly Uniform Microspherical Porous Structure.

This study presents a biomimetic 3D customizable artificial vascular graft with a highly porous and uniform microscale structure. The structural features were obtained by dip coating of a highly close-packed microsphere suspension on a 3D printed sacrificial template. Considering the structured arrangement of microspherical porogens in the coating layer, the microsphere-leached constructs showed higher uniformity and porosity than the conventionally particulate-leached structures, leading to ultrasoft mechanical compliance. Considering biomechanical compatibility, the resulting elastic moduli were at the sub-MPa level, comparable with those of native vascular tissues. In addition, the developed porous graft was reinforced selectively at the edge regions using a nonporous coating to secure its practical sutureability for clinical use. The sufficiently low cytotoxicity was clinically confirmed to alleviate the stiffness mismatch issues at the anastomotic interface between the native tissue and the artificial graft, thus overcoming the relevant clinical complications. Furthermore, the overall superior properties could be implemented on the 3D printed template for patient-specific medicare, thus implying the manufacturability of patient-specific vascular grafts.

Biomedical Alloys and Physical Surface Modifications: A Mini-Review.

Biomedical alloys are essential parts of modern biomedical applications. However, they cannot satisfy the increasing requirements for large-scale production owing to the degradation of metals. Physical surface modification could be an effective way to enhance their biofunctionality. The main goal of this review is to emphasize the importance of the physical surface modification of biomedical alloys. In this review, we compare the properties of several common biomedical alloys, including stainless steel, Co-Cr, and Ti alloys. Then, we introduce the principle and applications of some popular physical surface modifications, such as thermal spraying, glow discharge plasma, ion implantation, ultrasonic nanocrystal surface modification, and physical vapor deposition. The importance of physical surface modifications in improving the biofunctionality of biomedical alloys is revealed. Future studies could focus on the development of novel coating materials and the integration of various approaches.

Chitosan ducts fabricated by extrusion-based 3D printing for soft-tissue engineering.

Three kinds of methods based on extrusion and 3D printing and different acidic solutions (formic acid (FA), acetic acid (AA), glycolic acid (GA) and lactic acid (LA)) were applied for manufacturing the CS ducts. The tensile properties and preliminary cytotoxicity were measured for selecting the optimal ratio of CS slurry. The 3D printability of CS slurry was also studied. The tensile strength, Young's modulus, and fracture strain were tested for evaluating the degree of mechanical matching to soft-tissue. The optimal solvent to CS was 30 wt.% GA solution. The CS slurry possessing shear-thinning properties was suitable for 3D printing. The tensile strength, Young's modulus, and fracture strain of the CS rods were 10.98 ±â€¯0.61 MPa, 12.38 ±â€¯1.19 MPa, and 146.03 ±â€¯15.05 %, correspondingly. The CS ducts manufactured by 3D printing had an excellent mechanical matching to soft-tissue, outstanding biocompatibility and have great potential for soft-tissue restorations.

Design and development of metallic biomaterials with biological and mechanical biocompatibility.

In the present article, the recent trends in the research and development of metallic biomaterials are discussed with focus on the results obtained by the author's group. The design of biocompatible metallic biomaterials possessing excellent biological and mechanical properties, including titanium alloys with low Young's modulus, is reviewed with focus on Young's modulus, fatigue strength, and peculiar behavior. The evaluation of biological compatibility including cell viability and living tissue compatibility using animal models and surface modifications using bioactive ceramic and blood-compatible polymers are summarized. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 944-954, 2019.

Fabrication and Microassembly of a mm-Sized Floating Probe for a Distributed Wireless Neural Interface.

A new class of wireless neural interfaces is under development in the form of tens to hundreds of mm-sized untethered implants, distributed across the target brain region(s). Unlike traditional interfaces that are tethered to a centralized control unit and suffer from micromotions that may damage the surrounding neural tissue, the new free-floating wireless implantable neural recording (FF-WINeR) probes will be stand-alone, directly communicating with an external interrogator. Towards development of the FF-WINeR, in this paper we describe the micromachining, microassembly, and hermetic packaging of 1-mm³ passive probes, each of which consists of a thinned micromachined silicon die with a centered Ø(diameter) 130 µm through-hole, an Ø81 µm sharpened tungsten electrode, a 7-turn gold wire-wound coil wrapped around the die, two 0201 surface mount capacitors on the die, and parylene-C/Polydimethylsiloxane (PDMS) coating. The fabricated passive probe is tested under a 3-coil inductive link to evaluate power transfer efficiency (PTE) and power delivered to a load (PDL) for feasibility assessment. The minimum PTE/PDL at 137 MHz were 0.76%/240 µW and 0.6%/191 µW in the air and lamb head medium, respectively, with coil separation of 2.8 cm and 9 kΩ receiver (Rx) loading. Six hermetically sealed probes went through wireless hermeticity testing, using a 2-coil inductive link under accelerated lifetime testing condition of 85 °C, 1 atm, and 100%RH. The mean-time-to-failure (MTTF) of the probes at 37 °C is extrapolated to be 28.7 years, which is over their lifetime.

ß-Type titanium alloys for spinal fixation surgery with high Young's modulus variability and good mechanical properties.

Along with a high strength, ductility, and work hardening rate, a variable Young's modulus is crucial for materials used as implant rods in spinal fixation surgery. The potential in this context of Ti-(9,8,7)Cr-0.2O (mass%) alloys is reported herein. The microstructural and mechanical properties of the alloys were systematically examined as a function of their chromium content, and the ion release of the optimized alloy was investigated to assess its suitability as an implant material. In terms of the deformation-induced ω-phase transformation required for a variable Young's modulus, the balance between ß-phase stability and athermal ω-phase content is most favorable in the Ti-9Cr-0.2O alloy. In addition, this composition affords a high tensile strength (>1000MPa), elongation at break (∼20%), and work hardening rate to solution-treated (ST) samples. These excellent properties are attributed to the combined effects of deformation-induced ω-phase transformation, deformation twinning, and dislocation gliding. Furthermore, the ST Ti-9Cr-0.2O alloy proves resistant to metal ion release in simulated body fluid. This combination of a good biocompatibility, variable Young's modulus and a high strength, ductility, and work hardening rate is ideal for spinal fixation applications. STATEMENT OF SIGNIFICANCE: Extensive efforts have been devoted over the past decades to developing ß-type titanium alloys with low Young's moduli for biomedical applications. In spinal fixation surgery however, along with excellent mechanical properties, the spinal-support materials should possess high Young's modulus for showing small springback during surgery to facilitate manipulation but low Young's modulus close to bone once implanted to avoid stress shielding. None of currently used metallic biomaterials can satisfy these abovementioned requirements. In the present study, we have developed a novel alloy, Ti-9Cr-0.2O. Remarkably variable Young's modulus and excellent mechanical properties can be achieved in this alloy via phase transformations and complex deformation mechanisms, which makes the Ti-9Cr-0.2O preferred material for spinal fixation surgery.

Uniaxial and biaxial mechanical characterization of a prosthetic mesh at different length scales.

This study is aimed at a comprehensive experimental analysis of the mechanical behavior of a prosthetic mesh considering different length scales. Uniaxial and biaxial protocols are developed to evaluate global mechanical phenomena of the dry mesh. Furthermore, procedures for local deformation analysis and evaluation of corresponding homogenized kinematic measures are described. The global mechanical response of the prosthetic mesh is characterized by anisotropy, a nonlinear force response, hysteresis and preconditioning effects. The local deformation analysis allows to identify mesh specific phenomena related to mechanisms at the unit cell level. The global and the local kinematic responses of the mesh are seen to be directly related to clinical observations and help to understand associated complications, such as wrinkle formation, dislocation or erosion. In that sense, this study contributes to the analysis of mechanical biocompatibility of mesh implants and proposes protocols for comprehensive mesh product descriptions.

Mechanical biocompatibility of prosthetic meshes: a comprehensive protocol for mechanical characterization.

This study is aimed at a comprehensive and extensive characterization of the mechanical biocompatibility of mesh prostheses. A robust and simple experimental protocol and a set of parameters is proposed, addressing stiffness under uniaxial and biaxial loading conditions, anisotropy, influence of prior deformation history, local mismatch of deformation mechanisms, and changes in mechanical properties when embedded in a homogeneous matrix. These parameters can form the basis for comparison of different mesh types and for evaluation of their mechanical biocompatibility. Measurements were performed on nine mesh types used for hernia and/or pelvic repair, including heavier as well as lighter implants and covering a wide range of mechanical responses. A total of 93 experiments were performed and all parameters are represented for each mesh in a single diagram to facilitate the quantitative assessment of implant characteristics and their comparison. The mechanics of implants is a critical factor determining clinical performance which should be accounted for in mesh selection and for development of future implants.