Plasma Polishing as a New Polishing Option to Reduce the Surface Roughness of Porous Titanium Alloy for 3D Printing.

Porous titanium alloy implants with simulated trabecular bone fabricated by 3D printing technology have broad prospects. However, due to the fact that some powder adheres to the surface of the workpiece during the manufacturing process, the surface roughness in direct printing pieces is relatively high. At the same time, since the internal pores of the porous structure cannot be polished by conventional mechanical polishing, an alternative method needs to be found. As a surface technology, plasma polishing technology is especially suitable for parts with complex shapes that are difficult to polish mechanically. It can effectively remove particles and fine splash residues attached to the surface of 3D printed porous titanium alloy workpieces. Therefore, it can reduce surface roughness. Firstly, titanium alloy powder is used to print the porous structure of the simulated trabecular bone with a metal 3D printer. After printing, heat treatment, removal of the supporting structure, and ultrasonic cleaning is carried out. Then, plasma polishing is performed, consisting of adding a polishing electrolyte with the pH set to 5.7, preheating the machine to 101.6 °C, fixing the workpiece on the polishing fixture, and setting the voltage (313 V), current (59 A), and polishing time (3 min). After polishing, the surface of the porous titanium alloy workpiece is analyzed by a confocal microscope, and the surface roughness is measured. Scanning electron microscopy is used to characterize the surface condition of porous titanium. The results show that the surface roughness of the whole porous titanium alloy workpiece changed from Ra (average roughness) = 126.9 µm to Ra = 56.28 µm, and the surface roughness of the trabecular structure changed from Ra = 42.61 µm to Ra = 26.25 µm. Meanwhile, semi-molten powders and ablative oxide layers are removed, and surface quality is improved.

Biocompatibility and Cytotoxicity of Gold Nanoparticles: Recent Advances in Methodologies and Regulations.

Recent advances in the synthesis of metal nanoparticles (MeNPs), and more specifically gold nanoparticles (AuNPs), have led to tremendous expansion of their potential applications in different fields, ranging from healthcare research to microelectronics and food packaging. The properties of functionalised MeNPs can be fine-tuned depending on their final application, and subsequently, these properties can strongly modulate their biological effects. In this review, we will firstly focus on the impact of MeNP characteristics (particularly of gold nanoparticles, AuNPs) such as shape, size, and aggregation on their biological activities. Moreover, we will detail different in vitro and in vivo assays to be performed when cytotoxicity and biocompatibility must be assessed. Due to the complex nature of nanomaterials, conflicting studies have led to different views on their safety, and it is clear that the definition of a standard biosafety label for AuNPs is difficult. In fact, AuNPs' biocompatibility is strongly affected by the nanoparticles' intrinsic characteristics, biological target, and methodology employed to evaluate their toxicity. In the last part of this review, the current legislation and requirements established by regulatory authorities, defining the main guidelines and standards to characterise new nanomaterials, will also be discussed, as this aspect has not been reviewed recently. It is clear that the lack of well-established safety regulations based on reliable, robust, and universal methodologies has hampered the development of MeNP applications in the healthcare field. Henceforth, the international community must make an effort to adopt specific and standard protocols for characterisation of these products.

3D Tissue and Organ Printing-Hope and Reality.

Three-dimensional (3D) bioprinting is an emerging, groundbreaking strategy in tissue engineering, allowing the fabrication of living constructs with an unprecedented degree of complexity and accuracy. While this technique greatly facilitates the structuring of native tissue-like architectures, many challenges still remain to be faced. In this review, the fruits of recent research that demonstrate how advanced bioprinting technologies, together with inspiring creativity, can be used to address these challenges are presented and discussed. Next, the future of the field is discussed, in terms of expected developments, as well as possible directions toward the realization of the vision of fully functional, engineered tissues, and organs. Last, a few hypothetical scenarios for the role 3D bioprinting may play in future tissue engineering are depicted, with an emphasis on its impact on tomorrow's regenerative medicine.

Preliminary Evaluation of 3D Printed Chitosan/Pectin Constructs for Biomedical Applications.

In the present study, chitosan (CS) and pectin (PEC) were utilized for the preparation of 3D printable inks through pneumatic extrusion for biomedical applications. CS is a polysaccharide with beneficial properties; however, its printing behavior is not satisfying, rendering the addition of a thickening agent necessary, i.e., PEC. The influence of PEC in the prepared inks was assessed through rheological measurements, altering the viscosity of the inks to be suitable for 3D printing. 3D printing conditions were optimized and the effect of different drying procedures, along with the presence or absence of a gelating agent on the CS-PEC printed scaffolds were assessed. The mean pore size along with the average filament diameter were measured through SEM micrographs. Interactions among the characteristic groups of the two polymers were evident through FTIR spectra. Swelling and hydrolysis measurements confirmed the influence of gelation and drying procedure on the subsequent behavior of the scaffolds. Ascribed to the beneficial pore size and swelling behavior, fibroblasts were able to survive upon exposure to the ungelated scaffolds.

The Effect of Chitosan in Wound Healing: A Systematic Review.

OBJECTIVE: To systematically review the effectiveness of chitosan in wound healing. DATA SOURCES: References were retrieved from PubMed, EMBASE, the Cochrane library, and Web of Science based on Medical Subject Headings and keywords ("chitosan" OR "chitin" OR "poliglusam" AND "wound healing"). STUDY SELECTION: Eligible articles were randomized controlled trials (RCTs) that required interventions for chitosan and its derivative dressings and included endpoints associated with wound healing. In summary, five RCTs (N = 319) were included in the final analysis. DATA SYNTHESIS: Only two RCTS (40%) reported significant beneficial effects of chitosan on wound healing compared with conventional gauze dressings (eg, tulle gras, petroleum jelly). The remaining three studies reported that chitosan had no significant effect on clinical wound healing compared with other biologic dressings (eg, alginate, hydrocolloid). CONCLUSIONS: Although the number of trials of new chitosan dressings has been increasing, studies on the relationship between chitosan and wound healing have been limited. Current data suggest that chitosan does not slow wound healing. However, the small number of available trials restricted adequate interpretation of the existing results. Future research needs to be rigorously designed to confirm any clinically relevant effect of chitosan in wound healing.

Load Sharing and Endplate Pressure Distribution in Anterior Interbody Fusion Influenced by Graft Choice.

BACKGROUND: Cage subsidence is a known complication of spinal fusion. Various aspects of cage design have been investigated for their influence on cage subsidence, whereas the potential contribution of graft material to load sharing is often overlooked. We aimed to determine whether graft in the aperture affects endplate pressure distribution. METHODS: The pressure distributions of a polyetheretherketone interbody cage with 3 different aperture graft conditions were evaluated: empty, demineralized bone matrix, and supercritical CO2-treated allograft bone crunch (SCCO2). RESULTS: Graft materials contributed as much as half the load transmission for SCCO2, whereas demineralized bone matrix contributed one third. Endplate areas in contact with the cage demonstrated decreased areas within the highest-pressure spectrum with SCCO2 graft materials compared with empty cages. CONCLUSIONS: Graft choice plays a role in reducing peak endplate pressures. This finding is relevant to implant subsidence, as well as graft loading and remodeling.

Comparative Study of Silk-Based Magnetic Materials: Effect of Magnetic Particle Types on the Protein Structure and Biomaterial Properties.

This study investigates combining the good biocompatibility and flexibility of silk protein with three types of widely used magnetic nanoparticles to comparatively explore their structures, properties and potential applications in the sustainability and biomaterial fields. The secondary structure of silk protein was quantitatively studied by infrared spectroscopy. It was found that magnetite (Fe3O4) and barium hexaferrite (BaFe12O19) can prohibit ß-sheet crystal due to strong coordination bonding between Fe3+ ions and carboxylate ions on silk fibroin chains where cobalt particles showed minimal effect. This was confirmed by thermal analysis, where a high temperature degradation peak was found above 640 °C in both Fe3O4 and BaFe12O19 samples. This was consistent with the magnetization studies that indicated that part of the Fe in the Fe3O4 and BaFe12O19 was no longer magnetic in the composite, presumably forming new phases. All three types of magnetic composites films maintained high magnetization, showing potential applications in MRI imaging, tissue regeneration, magnetic hyperthermia and controlled drug delivery in the future.

PEEK versus titanium cages in lateral lumbar interbody fusion: a comparative analysis of subsidence.

OBJECTIVE: The authors have provided a review of radiographic subsidence after lateral lumbar interbody fusion (LLIF) as a comparative analysis between titanium and polyetheretherketone (PEEK) cages. Many authors describe a reluctance to use titanium cages in spinal fusion secondary to subsidence concerns due to the increased modulus of elasticity of metal cages. The authors intend for this report to provide observational data regarding the juxtaposition of these two materials in the LLIF domain. METHODS: A retrospective review of a prospectively maintained database identified 113 consecutive patients undergoing lateral fusion for degenerative indications from January to December 2017. The surgeons performing the cage implantations were two orthopedic spine surgeons and two neurosurgeons. Plain standing radiographs were obtained at 1-2 weeks, 8-12 weeks, and 12 months postoperatively. Using a validated grading system, interbody subsidence into the endplates was graded at these time points on a scale of 0 to III. The primary outcome measure was subsidence between the two groups. Secondary outcomes were analyzed as well. RESULTS: Of the 113 patients in the sample, groups receiving PEEK and titanium implants were closely matched at 57 and 56 patients, respectively. Cumulatively, 156 cages were inserted and recombinant human bone morphogenetic protein-2 (rhBMP-2) was used in 38.1%. The average patient age was 60.4 years and average follow-up was 75.1 weeks. Subsidence in the titanium group in this study was less common than in the PEEK cage group. At early follow-up, groups had similar subsidence outcomes. Statistical significance was reached at the 8- to 12-week and 52-week follow-ups, demonstrating more subsidence in the PEEK cage group than the titanium cage group. rhBMP-2 usage was also highly correlated with higher subsidence rates at all 3 follow-up time points. Age was correlated with higher subsidence rates in univariate and multivariate analysis. CONCLUSIONS: Titanium cages were associated with lower subsidence rates than PEEK cages in this investigation. Usage of rhBMP-2 was also robustly associated with higher endplate subsidence. Each additional year of age correlated with an increased subsidence risk. Subsidence in LLIF is likely a response to a myriad of factors that include but are certainly not limited to cage material. Hence, the avoidance of titanium interbody implants secondary solely to concerns over a modulus of elasticity likely overlooks other variables of equal or greater importance.

The Development of Extracellular Vesicle-Integrated Biomaterials for Bone Regeneration.

The clinical need for effective bone regeneration remains in huge demands. Although autologous and allogeneic bone grafts are generally considered "gold standard" treatments for bone defects, these approaches may result in various complications. Furthermore, safety considerations of gene- and cell-based therapies require further clarification and approval from regulatory authorities. Therefore, developing new therapeutic biomaterials that can empower endogenous regenerative properties to accelerate bone repair and regeneration is of great significance. Extracellular vesicles (EVs) comprise a heterogeneous population of naturally derived nanoparticles that play a critical role in mediating cell-cell communication. The vast amount of biological processes that EVs are involved in, such as immune modulation, senescence, and angiogenesis, and the versatility of manner in which they can influence the behavior of recipient cells make EVs an interesting source for both diagnostic and therapeutic applications. Advancement of knowledge in the fields of immunology and cell biology has sparked the exploration of the potential of EVs in the field of regenerative medicine. EVs travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating the recruitment, proliferation, and differentiation of recipient cells. Numerous studies have demonstrated the pivotal role of EVs in tissue regeneration both in vitro and in vivo. In this chapter, we will outline current knowledge surrounding EVs, summarize their functional roles in bone regenerative medicine, and elaborate on potential application and challenges of EV-integrated biomaterials in bone tissue engineering.

In Vivo Evaluation of the Biocompatibility of Biomaterial Device.

Biomaterials are widely used to produce devices for regenerative medicine. After its implantation, an interaction between the host immune system and the implanted biomaterial occurs, leading to biomaterial-specific cellular and tissue responses. These responses may include inflammatory, wound healing responses, immunological and foreign-body reactions, and even fibrous encapsulation of the implanted biomaterial device. In fact, the cellular and molecular events that regulate the success of the implant and tissue regeneration are played at the interface between the foreign body and the host inflammation, determined by innate and adaptive immune responses. This chapter focuses on host responses that must be taken into consideration in determining the biocompatibility of biomaterial devices when implanted in vivo of animal models.

Biocompatibility of Materials for Biomedical Engineering.

In the tissue engineering research field, nanobiomaterials highlight the impact of novel bioactive materials in both current applications and their potentials in future progress for tissue engineering and regenerative medicine. Tissue engineering is a well-investigated and challenging biomedical field, with promising perspectives to improve and support quality of life for the patient. To assess the response of those extracellular matrices (ECMs), induced by biomedical materials, this review will focus on cell response to natural biomaterials for biocompatibility.

A Review of Design Considerations for Hemocompatibility within Microfluidic Systems.

The manipulation of blood within in vitro environments presents a persistent challenge, due to the highly reactive nature of blood, and its multifaceted response to material contact, changes in environmental conditions, and stimulation during handling. Microfluidic Lab-on-Chip systems offer the promise of robust point-of-care diagnostic tools and sophisticated research platforms. The capacity for precise control of environmental and experimental conditions afforded by microfluidic technologies presents unique opportunities that are particularly relevant to research and clinical applications requiring the controlled manipulation of blood. A critical bottleneck impeding the translation of existing Lab-on-Chip technology from laboratory bench to the clinic is the ability to reliably handle relatively small blood samples without negatively impacting blood composition or function. This review explores design considerations critical to the development of microfluidic systems intended for use with whole blood from an engineering perspective. Material hemocompatibility is briefly explored, encompassing common microfluidic device materials, as well as surface modification strategies intended to improve hemocompatibility. Operational hemocompatibility, including shear-induced effects, temperature dependence, and gas interactions are explored, microfluidic sample preparation methodologies are introduced, as well as current techniques for on-chip manipulation of the whole blood. Finally, methods of assessing hemocompatibility are briefly introduced, with an emphasis on primary hemostasis and platelet function.

Growing a backbone - functional biomaterials and structures for intervertebral disc (IVD) repair and regeneration: challenges, innovations, and future directions.

Back pain and associated maladies can account for an immense amount of healthcare cost and loss of productivity in the workplace. In particular, spine related injuries in the US affect upwards of 5.7 million people each year. The degenerative disc disease treatment almost always arises due to a clinical presentation of pain and/or discomfort. Preferred conservative treatment modalities include the use of non-steroidal anti-inflammatory medications, physical therapy, massage, acupuncture, chiropractic work, and dietary supplements like glucosamine and chondroitin. Artificial disc replacement, also known as total disc replacement, is a treatment alternative to spinal fusion. The goal of artificial disc prostheses is to replicate the normal biomechanics of the spine segment, thereby preventing further damage to neighboring sections. Artificial functional disc replacement through permanent metal and polymer-based components continues to evolve, but is far from recapitulating native disc structure and function, and suffers from the risk of unsuccessful tissue integration and device failure. Tissue engineering and regenerative medicine strategies combine novel material structures, bioactive factors and stem cells alone or in combination to repair and regenerate the IVD. These efforts are at very early stages and a more in-depth understanding of IVD metabolism and cellular environment will also lead to a clearer understanding of the native environment which the tissue engineering scaffold should mimic. The current review focusses on the strategies for a successful regenerative scaffold for IVD regeneration and the need for defining new materials, environments, and factors that are so finely tuned in the healthy human intervertebral disc in hopes of treating such a prevalent degenerative process.

Workshop on the characterization of fiber-based scaffolds: Challenges, progress, and future directions.

A critical component of many tissue-engineered medical products (TEMPs) is the scaffold or biomaterial. The industry's understanding of scaffold properties and their influence on cell behavior has advanced, but our technical capability to reliably characterize scaffolds requires improvement, especially to enable large-scale manufacturing. In response to the key findings from the 2013 ASTM International Workshop of Standards and Measurements for Tissue Engineering Scaffolds, the National Institute of Standards and Technology (NIST), ASTM International, BiofabUSA, and the Standards Coordinating Body (SCB) organized a workshop in 2018 titled, "Characterization of Fiber-Based Scaffolds". The goal was to convene a group of 40 key industry stakeholders to identify major roadblocks in measurements of fiber-based scaffold properties. This report provides an overview of the findings from this collaborative workshop. The four major consensus findings were that (a) there is need for a documentary standard guide that would aid developers in the selection of test methods for characterizing fiber-based scaffolds; (b) there is a need for a strategy to assess the quality of porosity and pore size measurements, which could potentially be ameliorated by the development of a reference material; (b) there are challenges with the lexicon used to describe and assess scaffolds; and (d) the vast array of product applications makes it challenging to identify consensus test methods. As a result of these findings, a working group was formed to develop an ASTM Standard Guide for Characterizing Fiber-Based Constructs that will provide developers guidance on selecting measurements for characterizing fiber-based scaffolds.

A three-dimensional printed photopolymer resin implant for orbital rehabilitation for evisceration / Implante de resina fotocurável para evisceração produzido por impressora tridimensional

ABSTRACT Purpose: To evaluate the biocompatibility of three-dimensional (3D) printed orbital spheres for evisceration. Materials: A total of 10 consecutive patients (eight females and two males; mean age, 46.8 ± 14.2 years) underwent evisceration of blind painful eyes. 3D spherical implants produced by a rapid prototype machine were used to restore orbital volume. The implants were produced from a commercially available photocurable resin (Fullcure®). Systemic toxicity was evaluated by comparing serum biochemical measurements (creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, albumin, creatinine, urea, alkaline phosphatase, and C-reactive protein) before and at 12 months after surgery. Local toxicity was assessed by the evaluation of signs of socket inflammation at the first postoperative month. Changes in implant size were determined by computed tomography scans at 2 and 12 months after surgery. Results: The postoperative evaluations were uneventful. The biochemical evaluation showed no significant changes after surgery. None of the patients presented signs of orbital implant inflammation, infection, exposure, or extrusion. Computed tomography scan evaluations revealed no changes in implant size. Conclusion: To the best of our knowledge, this is the first phase-1 clinical study to certify the biocompatibility of the Fullcure resin for orbital implants in humans. The 3D printing technology permits fast and accurate production of implants for this purpose.

RESUMO Objetivos: Avaliar a biocompatibilidade das esferas produzidas por impressora tridimensional em evisceração. Pacientes e métodos: Evisceração por olho cego doloroso foi realizada em 10 pacientes consecutivos (8 mulheres, idade média: 46.8 ± 14.2 anos). Os implantes esféricos foram produzidos pelo sistema de prototipagem rápida utilizando dados tridimensionais computadorizados. O material utilizado para produção dos implantes foi a resina fotocurável Fullcure®. A avaliação da toxicidade sistêmica do material foi realizada por meio da dosagem de marcadores bioquímicos (creatina fosfoquinase, aspartato aminotransferase, alanina aminotransferase, albumina, creatinina, ureia, fosfatase alcalina, e proteína C-reactiva) antes da cirurgia e aos 12 meses de pós-operatorio. A avaliação da toxicidade local foi realizada por meio do registro qualitativo dos sinais inflamatórios no lado operado durante o primeiro mês de pós-operatório. O tamanho dos implantes foi medido em tomografias computadorizadas (CT) aos 2 e 12 meses de pós-operatório. Resultados: A avaliação bioquímica mostrou que os marcadores estudados não sofreram alterações significativas após a cirurgia. Nenhum paciente apresentou sinais de inflamação atípica, infecção, exposição ou extrusão. A avaliação tomográfica não demonstrou mudanças nos tamanhos dos implantes. Conclusão: O presente trabalho é o primeiro estudo clínico realizado para atestar a biocompatibilidade dos implantes orbitais de resina fotocurável Fullcure. A produção dos implantes pela técnica de impressão tridimensional, utilizando essa resina, permite a disponibilização rápida e acurada do produto final

A three-dimensional printed photopolymer resin implant for orbital rehabilitation for evisceration.

PURPOSE: To evaluate the biocompatibility of three-dimensional (3D) printed orbital spheres for evisceration. MATERIALS: A total of 10 consecutive patients (eight females and two males; mean age, 46.8 ± 14.2 years) underwent evisceration of blind painful eyes. 3D spherical implants produced by a rapid prototype machine were used to restore orbital volume. The implants were produced from a commercially available photocurable resin (Fullcure®). Systemic toxicity was evaluated by comparing serum biochemical measurements (creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, albumin, creatinine, urea, alkaline phosphatase, and C-reactive protein) before and at 12 months after surgery. Local toxicity was assessed by the evaluation of signs of socket inflammation at the first postoperative month. Changes in implant size were determined by computed tomography scans at 2 and 12 months after surgery. RESULTS: The postoperative evaluations were uneventful. The biochemical evaluation showed no significant changes after surgery. None of the patients presented signs of orbital implant inflammation, infection, exposure, or extrusion. Computed tomography scan evaluations revealed no changes in implant size. CONCLUSION: To the best of our knowledge, this is the first phase-1 clinical study to certify the biocompatibility of the Fullcure resin for orbital implants in humans. The 3D printing technology permits fast and accurate production of implants for this purpose.

Reliability of parylene-based multi-electrode arrays chronically implanted in adult rat brains, and evidence of electrical stimulation on contact impedance.

OBJECTIVE: The goal of this study was to evaluate the long-term behavior of the surface electrode through electrochemical characterization and follow-up of implanted parylene/platinum microelectrodes. APPROACH: To this aim, we designed and manufactured specific planar electrodes for cortical implantation for a rat model. This work was included in the INTENSE® project, one of the goals of which was to prove the feasibility of selective neural recording or stimulation with cuff electrodes around the vagus nerve. MAIN RESULTS: After a 12-week implantation in a rat model, we can report that these microelectrodes have withstood in vivo use. Regarding the biocompatibility of the electrodes (materials and manufacturing process), no adverse effect was reported. Indeed, after the three-month implantation, we characterized limited tissue reaction beneath the electrodes and showed an increase and a stabilization of their impedance. Interestingly, the follow-up of the electrochemical impedance combined with electrical stimulation highlighted a drop in the impedance up to 60% at 1 kHz after ten minutes of electrical stimulation at 110 Hz. SIGNIFICANCE: This study gives evidence of the biocompatibility of the parylene platinum contact array designed for the project and confirms the effect of stimulation on the contact impedance.

Improving the biocompatibility of biomaterial constructs and constructs delivering cells for the pelvic floor.

PURPOSE OF REVIEW: Interactions between biomaterials and biomaterial-delivering cells and the host tissues are complexly affected by the material itself, the ultrastructure of the overall construct and cells and other bioactive factors involved. The aim of this review is to review the current understanding on the definitions of biocompatibility and current advances in improving biocompatability of tissue-engineered constructs. RECENT FINDINGS: Some synthetic materials are associated with more foreign body reactions compared with natural materials; however, they allow fabrication of materials with a great diversity of physical and mechanical properties. Material design strategies can be tailored to mimic the natural extracellular matrix topography. There are also advancements in the pharmacological functionalization of materials with improved angiogenic potential that can lead to better tissue response. Stem cells are also used to improve the tissue response of tissue-engineered materials; however, the recent regulations on regenerative medicine products necessitate significant regulatory approval processes for these. SUMMARY: The biggest challenge faced in translation of tissue-engineered constructs into clinical practice relates to their engraftment and poor tissue integration into the challenging wound bed of the pelvic floor. Biocompatibility of tissue engineered constructs can theoretically be improved by the incorporation of bioactive agents, such as vitamins C or oestradiol.

Unlocalized crack initiation and propagation in staggered biomaterials.

Many types of tissues in living organisms exhibit a combination of different properties to fulfil their mechanical functions in complex environments. Nacre with more than 90% brittle and hard phase and a little protein matrix, exhibits high strength and toughness, which is difficult to achieve in artificial materials. Researchers have shown that the toughness of nacre is related to the cracking process. Most of them, however, assume an obvious pre-existing crack on the model and the initiation of the microscopical pre-existing crack is not considered yet. Based on fracture mechanics with the cohesive zone model, we reveal the mechanism of the crack initiation and propagation pattern in staggered biomaterials without any pre-existing crack. The simulation result shows that there are two crack propagation modes: localized mode and unlocalized mode. A crack initiates and propagates in a small area in the localized mode, while cracks initiate at different points and propagate in various paths in the unlocalized mode. The crack initiation mechanism from the intrinsic properties of the material is clarified using energy based stability analysis. The result shows that the shear interfacial mechanism significantly delays the crack initiation.