Long-term Biocompatibility Research Articles

Biocompatible dipeptide coated on Pt/PEDOT:PSS modified silicon probes for tissues rejection alleviation

The implantable neural probe is an indispensable tool to record the high-quality spike signals. However, the high interface impedance of electrode-tissue and severe tissue rejection degrade the signal quality and shorten the service life of neural probes in-vivo. Here, a Pt/PEDOT:PSS modified silicon probes with biocompatible dipeptide layer is proposed to avoid these issues. First, a bilayer Pt/PEDOT:PSS was electrochemically deposited on gold microelectrodes to reduce the impedance. Then, a layer of dipeptide was deposited on the modified probe by physical vapor deposition (PVD) to mitigate tissue rejection. The electrochemical results show that the electrode-tissue interface impedance can be reduced by two orders of magnitude by the Pt/PEDOT:PSS modification, with negligible impedance variation by the following dipeptide layer. From the in-vitro accelerated aging, it can be inferred that the Pt/PEDOT:PSS/dipeptide modified microelectrodes can survive for more than 10 weeks. In-vitro cytotoxicity experiments show that the dipeptide can help improve the biocompatibility. Lastly, in-vivo implantation further proves that dipeptide may contribute to the realization of lower tissues rejection and higher signal-to-noise ratio within 8 weeks of implantation. The widely used silicon neural probes with the Pt/PEDOT:PSS modification and overall dipeptide coating provide as a new solution for long-term biocompatibility and high-quality neural signals.

Revolutionizing Eye Care: Exploring the Potential of Microneedle Drug Delivery

Microneedle technology revolutionizes ocular drug delivery by addressing challenges in treating ocular diseases. This review explores its potential impact, recent advancements, and clinical uses. This minimally invasive technique offers precise control of drug delivery to the eye, with various microneedle types showing the potential to penetrate barriers in the cornea and sclera, ensuring effective drug delivery. Recent advancements have improved safety and efficacy, offering sustained and controlled drug delivery for conditions like age-related macular degeneration and glaucoma. While promising, challenges such as regulatory barriers and long-term biocompatibility persist. Overcoming these through interdisciplinary research is crucial. Ultimately, microneedle drug delivery presents a revolutionary method with the potential to significantly enhance ocular disease treatment, marking a new era in eye care.

Encapsulation of the PHMB with nanoliposome and attachment to wound dressing for long-term antibacterial activity and biocompatibility.

Concentration control of some drug are used commonly however their uncontrolled concentration renders severe side effects. Therefore, it is substantial to come up with innovation release control methods. There is a strong affinity between the phospholipid of nanoliposomes and wool cells which facilitate the diffusion of liposomes into the wool structure. On the other hand, polyhexamethylene biguanide (PHMB) has gained popularity as an antibacterial agent; however, the compound's cytotoxicity has limited its usefulness. By compounding these facts, this work introduces a novel method for sustained drug release via internalization. In this method, PHMB was detained into nanoliposomes infiltrated the wool to generate an extremely regulated release, which was established using various techniques. SEM pictures demonstrated effective absorption of nanoliposome-encapsulated PHMB within the wool fabric. The developed wound dressing showed a sustained drug release, and consequently, perfect biocompatibility and enduring antibacterial activity.

Preliminary Long-Term Biocompatibility Assessment of Penn State University Child Pump

Preliminary Long-Term Biocompatibility Assessment of Penn State University Child Pump

Biocompatible triboelectric energy generators (BT-TENGs) for energy harvesting and healthcare applications.

Electronic waste (e-waste) has become a significant environmental and societal challenge, necessitating the development of sustainable alternatives. Biocompatible and biodegradable electronic devices offer a promising solution to mitigate e-waste and provide viable alternatives for various applications, including triboelectric nanogenerators (TENGs). This review provides a comprehensive overview of recent advancements in biocompatible, biodegradable, and implantable TENGs, emphasizing their potential as energy scavengers for healthcare devices. The review delves into the fabrication processes of self-powered TENGs using natural biopolymers, highlighting their biodegradability and compatibility with biological tissues. It further explores the biomedical applications of ultrasound-based TENGs, including their roles in wound healing and energy generation. Notably, the review presents the novel application of TENGs for vagus nerve stimulation, demonstrating their potential in neurotherapeutic interventions. Key findings include the identification of optimal biopolymer materials for TENG fabrication, the effectiveness of TENGs in energy harvesting from physiological movements, and the potential of these devices in regenerative medicine. Finally, the review discusses the challenges in scaling up the production of implantable TENGs from biomaterials, addressing issues such as mechanical stability, long-term biocompatibility, and integration with existing medical devices, outlining future research opportunities to enhance their performance and broaden their applications in the biomedical field.

Application of Carbon Nanomaterials to Enhancing Tumor Immunotherapy: Current Advances and Prospects.

Recent advances in tumor immunotherapy have highlighted the pivotal role of carbon nanomaterials, such as carbon dots, graphene quantum dots, and carbon nanotubes. This review examines the unique benefits of these materials in cancer treatment, focusing on their mechanisms of action within immunotherapy. These include applications in immunoregulation, recognition, and enhancement. We explore how these nanomaterials when combined with specific biomolecules, can form immunosensors. These sensors are engineered for highly sensitive and specific detection of tumor markers, offering crucial support for early diagnosis and timely therapeutic interventions. This review also addresses significant challenges facing carbon nanomaterials in clinical settings, such as issues related to long-term biocompatibility and the hurdles of clinical translation. These challenges require extensive ongoing research and discussion. This review is of both theoretical and practical importance, aiming to promote using carbon nanomaterials in tumor immunotherapy, potentially transforming clinical outcomes and enhancing patient care.

Sustainable Nanofibril Interfaces for Strain-Resilient and Multimodal Porous Bioelectronics.

Porous soft bioelectronics have attracted significant attention due to their high breathability, long-term biocompatibility, and other unique features inaccessible in nonporous counterparts. However, fabricating high-quality multimodal bioelectronic components that operate stably under strain on porous substrates, along with integrating microfluidics for sweat management, remains challenging. In this study, cellulose nanofibrils (CNF) are explored, biomass-derived sustainable biomaterials, as nanofibril interfaces with unprecedented interfacial robustness to enable high-quality printing of strain-resilient bioelectronics on porous substrates by reducing surface roughness and creating mechanical heterogeneity. Also, CNF-based microfluidics can provide continuous sweat collection and refreshment, crucial for accurate biochemical sensing. Building upon these advancements, a multimodal porous wearable bioelectronic system is further developed capable of simultaneously detecting electrocardiograms and glucose and beta-hydroxybutyrate in sweat for monitoring energy metabolism and consumption. This work introduces novel strategies for fabricating high-quality, strain-resilient porous bioelectronics with customizable multimodalities to meet arising personalized healthcare needs.

Nanoparticle-Enabled Zn-0.1Mg Alloy with Long-Term Stability, Refined Degradation, and Favorable Biocompatibility for Biodegradable Implant Devices.

Zinc-based alloys, specifically Zn-Mg, have garnered considerable attention as promising materials for biodegradable implants due to their favorable mechanical strength, appropriate corrosion rate, and biocompatibility. Nevertheless, the alloy's lack of mechanical stability and integrity, resulting from ductility loss induced by age hardening at room temperature, hampers its practical bioapplication. In this study, ceramic nanoparticles have been successfully incorporated into the Zn-Mg alloy system, leading to a significant improvement in long-term stability as well as mechanical strength and ductility. In addition, this study represents the first investigation of Zn-based nanocomposites both in vitro and in vivo to comprehend the influence of nanoparticles on the degradation behavior and biocompatibility of the Zn system. The findings indicate that the incorporation of WC nanoparticles effectively refines and stabilizes the degradation behavior of Zn-Mg without negatively impacting the cytocompatibility of the alloy. The subcutaneous implantation and femoral implantation further prove the benefits of nanoparticle incorporation and found no negative effects. Collectively, Zn-Mg-WC nanocomposites yield great potential for implant usage.

Characterization of a conductive hydrogel@Carbon fibers electrode as a novel intraneural interface

Peripheral neural interfaces facilitate bidirectional communication between the nervous system and external devices, enabling precise control for prosthetic limbs, sensory feedback systems, and therapeutic interventions in the field of Bioelectronic Medicine. Intraneural interfaces hold great promise since they ensure high selectivity in communicating only with the desired nerve fascicles. Despite significant advancements, challenges such as chronic immune response, signal degradation over time, and lack of long-term biocompatibility remain critical considerations in the development of such devices. Here we report on the development and benchtop characterization of a novel design of an intraneural interface based on carbon fiber bundles. Carbon fibers possess low impedance, enabling enhanced signal detection and stimulation efficacy compared to traditional metal electrodes. We provided a 3D-stabilizing structure for the carbon fiber bundles made of PEDOT:PSS hydrogel, to enhance the biocompatibility between the carbon fibers and the nervous tissue. We further coated the overall bundles with a thin layer of elastomeric material to provide electrical insulation. Taken together, our results demonstrated that our electrode possesses adequate structural and electrochemical properties to ensure proper stimulation and recording of peripheral nerve fibers and a biocompatible interface with the nervous tissue.

Five-day Wearable Respiratory Support With a Novel Ambulatory Pulmonary Assist System in an Awake Ovine Model.

The pulmonary assist system (PAS) is a wearable respiratory support system that is currently under development for patients with chronic lung disease as a bridge to lung transplantation or as destination therapy. This study evaluates the long-term performance and biocompatibility of the PAS in a 5-d awake, ovine model. The PAS was attached to normal sheep in venovenous configuration. Components of the PAS included a 0.9 m2 surface area oxygenator and a lightweight, battery-powered axial flow pump. The system was also tested using the Abbott PediMag as the control pump. Each sheep was supported on the PAS for 5 d with 2 L/min blood flow and 4 L/min sweep gas. Activated clotting times of 200-240 s were maintained using intravenous heparin. Pump performance, oxygen transfer, oxygenator resistance, and hematologic parameters were measured throughout the support. The PAS, either using the axial flow pump or PediMag (n = 4 each), was well tolerated by the sheep without signs of device-related organ damage or hemolysis. All the studies achieved the full, 5-d study duration. The oxygenator resistance remained consistent without significant clot formation in all experiments with an average resistance of 2.55 ± 0.10 mm Hg/(L/min). The system achieved an average oxygen transfer rate of 116.4 ± 5.5 mL/min, with an average Hb concentration of 9.2 ± 0.6 g/dL. White blood cell, platelet, and hematocrit levels also remained stable and within normal limits throughout the study period. The PAS provided 5 d of uncomplicated ambulatory respiratory support with minimal clot formation, stable gas exchange, blood flow resistance, and hematologic parameters.

A plasma electrolytic oxidation coating on high-purity Mg with excellent long-term degradation performance and biocompatibility

A neutral electrolyte was used to prepare plasma electrolytic oxidation (PEO) coatings on biodegradable high-purity Mg (HP-Mg). Formation mechanism, surface morphology, and chemical compositions of the PEO coating were investigated. It was found that a porous layer formed first at the low cell voltage with an outward-growth characteristic, and then a dense layer was inward formed after the cell voltage reached the critical voltage. The main compositions of the PEO coating were MgF2, K2MgF4, KMgF3, Mg3(PO4)2, and MgO. Electrochemical measurements were carried out in simulated body fluid (SBF) at 37 °C to evaluate the long-term degradation performance. The coated HP-Mg exhibited superior degradation properties, and the coating remained intact over 180 days of degradation. During the degradation process, the pores and microcracks within the coating would gradually be filled with degradation products, enhancing the coating adhesion strength. The results of the cytotoxicity test validated the biosafety of the coating. Besides, a high-quality coating can be fabricated on the surface of biodegradable orthopedic Mg screws using this PEO treatment. The PEO coating possessed excellent degradation performance and biocompatibility, showing great potential in the practical production of biodegradable Mg implants.

Synthetic and Natural Biomaterials in Veterinary Medicine and Ophthalmology: A Review of Clinical Cases and Experimental Studies.

In recent years, there has been a growing interest in 3D printing technology within the field of bioengineering. This technology offers the ability to create devices with intricate macro- and micro-geometries, as well as specific models. It has particularly gained attention for its potential in personalized medicine, allowing for the production of organ or tissue models tailored to individual patient needs. Further, 3D printing has opened up possibilities to manufacture structures that can substitute, complement, or enhance damaged or dysfunctional organic parts. To apply 3D printing in the medical field, researchers have studied various materials known as biomaterials, each with distinct chemical and physical characteristics. These materials fall into two main categories: hard and soft materials. Each biomaterial needs to possess specific characteristics that are compatible with biological systems, ensuring long-term stability and biocompatibility. In this paper, we aim to review some of the materials used in the biomedical field, with a particular focus on those utilized in veterinary medicine and ophthalmology. We will discuss the significant findings from recent scientific research, focusing on the biocompatibility, structure, applicability, and in vitro and in vivo biological characteristics of two hard and four soft materials. Additionally, we will present the current state and prospects of veterinary ophthalmology.

Intraoperative assessment of microimplantation-induced acute brain inflammation with titanium oxynitride-based plasmonic biosensor

Implantable devices for brain-machine interfaces and managing neurological disorders have experienced rapid growth in recent years. Although functional implants offer significant benefits, issues related to transient trauma and long-term biocompatibility and safety are of significant concern. Acute inflammatory reaction in the brain tissue caused by microimplants is known to be an issue but remains poorly studied. This study presents the use of titanium oxynitride (TiNO) nanofilm with defined surface plasmon resonance (SPR) properties for point-of-care characterizing of acute inflammatory responses during robot-controlled micro-neuro-implantation. By leveraging surface-enriched oxynitride, TiNO nanofilms can be biomolecular-functionalized through silanization. This label-free TiNO-SPR biosensor exhibits a high sensitivity toward the inflammatory cytokine interleukin-6 with a detection limit down to 6.3 fg ml−1 and a short assay time of 25 min. Additionally, intraoperative monitoring of acute inflammatory responses during microelectrode implantation in the mice brain has been accomplished using the TiNO-SPR biosensors. Through intraoperative cerebrospinal fluid sampling and point-of-care plasmonic biosensing, the rhythm of acute inflammatory responses induced by the robot-controlled brain microelectrodes implantation has been successfully depicted, offering insights into intraoperative safety assessment of invasive brain-machine interfaces.

Nanotechnology applications in breast implant manufacturing for improved durability and functionality

Breast implants are often used in restorative and cosmetic surgeries. However, the materials used for implants today could be better regarding biocompatibility and mechanical strength. It is possible to make composite biomaterials out of nanomaterials with better mechanical qualities than common implant materials like silicone elastomers and saline-filled shells. Researchers have found that adding carbon nanotubes, graphene, and hydroxyapatite nanoparticles to the shells of metal and silicone implants makes them much stronger, more flexible, and less likely to break. Researchers are also looking into polymer nanocomposites made of polycaprolactone and polylactic acid to see if they can break down better and integrate better with tissues. Changing the surface of implants at the nanoscale level can make them more biocompatible by controlling how proteins stick to the material and how cells interact with it. Animal tests with nanocoatings of polyacrylate, chitosan, and hyaluronic acid showed that they lowered the formation of capsules and inflammation. Antimicrobial nanoparticles, such as silver, zinc oxide, and antibiotics, are attached to the surfaces of implants to protect against infections and release drugs locally. Nanocontrast agents are used in high-resolution MRI and ultrasound images of implant shell integrity to get new imaging and diagnosis tools. By tracking biomarkers, nanostructured sensors could be used to find seromas, ruptures, and device failures with little to no damage. Much work has been done to show that different nanotechnologies can help breast implants in a pre-clinical setting. However, problems with regulation and standardization still need to be fixed before the implants can be used in people and made in large quantities. The process needs to be improved even more to make a lot of nanocomposite and etched surfaces. To make sure patients are safe, it is also important to do long-term biocompatibility and nanotoxicology tests. Nanotechnology has a lot of promise to change the way breast implants are made so that they look better and improve people's quality of life. This review examines nanotechnology's emerging applications for enhancing breast implants' durability and performance.

Long-term degradation performance and biocompatibility of plasma electrolytic oxidation coated Mg-0.45Ca-xZn alloys prepared using a fluoride-based electrolyte

In this work, plasma electrolytic oxidation (PEO) with a fluoride-based electrolyte was performed on Mg-0.45Ca-xZn (x = 0, 0.45, 1.0, 2.0 wt%) alloys to enhance their degradation properties. These PEO coatings were composed of a porous layer and a barrier layer for alloys with Zn ≥ 0.45 wt%, while the coating on Mg-0.45Ca alloy was consisted of a dense inner layer and a porous outer layer. The content of Zn in the alloy has no significant effect on the hardness, adhesion strength and composition of the PEO coating. All coated-Mg-0.45Ca-xZn samples in this work showed decent anti-degradation properties in the simulated body fluid (SBF). Among them, PEO coatings on Mg-0.45Ca-1.0Zn and Mg-0.45Ca-2.0Zn alloys could provide excellent protection to the substrate over 3 months and exhibited good biocompatibility with Grade 0–1 of cytotoxicity, which were expected to be applied in the biomedical field. Besides, PEO process in this work enabled a high-quality coating to be formed on Mg–Ca–Zn bone screws.

Emerging Trends in Nanomedicine: Carbon-Based Nanomaterials for Healthcare.

Carbon-based nanomaterials, such as carbon quantum dots (CQDs) and carbon 2D nanosheets (graphene, graphene oxide, and graphdiyne), have shown remarkable potential in various biological applications. CQDs offer tunable photoluminescence and excellent biocompatibility, making them suitable for bioimaging, drug delivery, biosensing, and photodynamic therapy. Additionally, CQDs' unique properties enable bioimaging-guided therapy and targeted imaging of biomolecules. On the other hand, carbon 2D nanosheets exhibit exceptional physicochemical attributes, with graphene excelling in biosensing and bioimaging, also in drug delivery and antimicrobial applications, and graphdiyne in tissue engineering. Their properties, such as tunable porosity and high surface area, contribute to controlled drug release and enhanced tissue regeneration. However, challenges, including long-term biocompatibility and large-scale synthesis, necessitate further research. Potential future directions encompass theranostics, immunomodulation, neural interfaces, bioelectronic medicine, and expanding bioimaging capabilities. In summary, both CQDs and carbon 2D nanosheets hold promise to revolutionize biomedical sciences, offering innovative solutions and improved therapies in diverse biological contexts. Addressing current challenges will unlock their full potential and can shape the future of medicine and biotechnology.

3D electronic implants in subretinal space: Long-term follow-up in rodents

Clinical results with photovoltaic subretinal prosthesis (PRIMA) demonstrated restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution matching the 100 μm pixel size. Since scaling the pixels below 75 μm in the current bipolar planar geometry will significantly limit the penetration depth of the electric field and increase stimulation threshold, we explore the possibility of using smaller pixels based on a novel 3-dimensional honeycomb-shaped design. We assessed the long-term biocompatibility and stability of these arrays in rats by investigating the anatomical integration of the retina with flat and 3D implants and response to electrical stimulation over lifetime – up to 32–36 weeks post-implantation in aged rats. With both flat and 3D implants, signals elicited in the visual cortex decreased after the day of implantation by more than 3-fold, and gradually recovered over the next 12–16 weeks. With 25 μm high honeycomb walls, the majority of bipolar cells migrate into the wells, while amacrine and ganglion cells remain above the cavities, which is essential for selective network-mediated stimulation of the retina. Retinal thickness and full-field stimulation threshold with 40 μm-wide honeycomb pixels were comparable to those with planar devices – 0.05 mW/mm2 with 10 ms pulses. However, fewer cells from the inner nuclear layer migrated into the 20 μm-wide wells, and stimulation threshold increased over 12–16 weeks, before stabilizing at about 0.08 mW/mm2. Such threshold is still significantly lower than 1.8 mW/mm2 with a previous design of flat bipolar pixels, confirming the promise of the 3D honeycomb-based approach to high resolution subretinal prosthesis.

Porous silicon and silica carriers for delivery of peptide therapeutics.

Peptides have gained tremendous popularity as biological therapeutic agents in recent years due to their favourable specificity, diversity of targets, well-established screening methods, ease of production, and lower cost. However, their poor physiological and storage stability, pharmacokinetics, and fast clearance have limited their clinical translation. Novel nanocarrier-based strategies have shown promise in overcoming these issues. In this direction, porous silicon (pSi) and mesoporous silica nanoparticles (MSNs) have been widely explored as potential carriers for the delivery of peptide therapeutics. These materials possess several advantages, including large surface areas, tunable pore sizes, and adjustable pore architectures, which make them attractive carriers for peptide delivery systems. In this review, we cover pSi and MSNs as drug carriers focusing on their use in peptide delivery. The review provides a brief overview of their fabrication, surface modification, and interesting properties that make them ideal peptide drug carriers. The review provides a systematic account of various studies that have utilised these unique porous carriers for peptide delivery describing significant in vitro and in vivo results. We have also provided a critical comparison of the two carriers in terms of their physicochemical properties and short-term and long-term biocompatibility. Lastly, we have concluded the review with our opinion of this field and identified key areas for future research for clinical translation of pSi and MSN-based peptide therapeutic formulations.

The cytotoxicity assessment of different clear aligner materials

Background/purposeInvisible orthodontic treatments are becoming increasingly popular, and numerous brands of invisible aligners are now available. However, concerns remain about the safety of the materials used in these products. This study aimed to assess the cytotoxic effects of both original and thermoformed thermoplastic materials used in orthodontic aligners on human periodontal ligament (HPDL) cells in vitro. Materials and methodsThe experiment used six different brands, each containing three types of thermoplastic materials, Polyethylene terephthalateco-1, 4-cyclohexylenedimethylene terephthalate (PETG), thermoplastic polyurethane (TPU), and copolyester polyethylene terephthalate (PET). The original sheets and the thermoformed materials were soaked in a culture medium for seven and fourteen days, and then applied to cultured human periodontal ligament cells. Cells were harvested on the first, third, and fifth days after application, and their viability was analyzed using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. ResultsThe findings revealed that some thermoformed materials, notably PETG, exhibited lower survival rates compared to their non-thermoformed versions. However, other materials such as TP and PET maintained over 70% cell viability, indicating only minor cytotoxic effects. ConclusionThese findings highlight the need for further research into the long-term biocompatibility of these materials but generally affirm their safety for use in orthodontic aligners under the tested conditions.

Long-Term Evaluation of Inserted Nanocomposite Hydrogel-Based Phosphorescent Oxygen Biosensors: Evolution of Local Tissue Oxygen Levels and Foreign Body Response.

Phosphorescence-based oxygen-sensing hydrogels are a promising platform technology for an upcoming generation of insertable biosensors that are smaller, softer, and potentially more biocompatible than earlier designs. However, much remains unknown about their long-term performance and biocompatibility in vivo. In this paper, we design and evaluate a range of hydrogel sensors that contain oxygen-sensitive phosphors stabilized by micro- and nanocarrier systems. These devices demonstrated consistently good performance and biocompatibility in young adult rats for over three months. This study thoroughly establishes the biocompatibility and long-term suitability of phosphorescence lifetime sensors in vivo, providing the groundwork for expansion of this platform technology into a family of small, unobtrusive biosensors for a range of clinically relevant metabolites.