Biocompatibility Issues Research Articles

Assessment of polyethersulfone and polyacrylonitrile hemodialysis clinical membranes: In situ synchrotron-based imaging of human serum proteins adsorption, interaction analyses, molecular docking and clinical inflammatory biomarkers investigations

While hemodialysis augments the physiological functions of the kidney in end stage renal disease (ESRD) patients, inherent membrane properties initiate life-threating biological episodes upon contact with blood. Membrane materials have different morphological and chemical properties that may become complement, leukocyte and even coagulation activators leading to several cardiovascular diseases due to biocompatibility issues upon contact with blood. The present study offers an in-depth understanding into two commonly used clinical polyethersulfone (PES) and polyacrylonitrile (PAN) membranes in Canadian hospitals and the effects of blood-membrane interactions on their biocompatibility, in terms of the initiation of blood activation and pro-inflammatory cytokine, from both experimental and theoretical standpoints. PES and PAN were thoroughly investigated to explore their susceptibility toward interaction with three human serum proteins. The extent of protein adsorption, and subsequent interactions on the membrane surfaces were investigated after ultrafiltration with human serum albumin (ALB), fibrinogen (FB) and transferrin (TR) proteins. The buildup of protein microparticles across different stratified membrane layers was probed using Synchrotron-based X-ray microtomography conducted with a biomedical imaging and therapy (BMIT 05ID-2) beamline at the Canada's national synchrotron light source facility. Furthermore, evidence of protein adhesion has been exhaustively investigated by surface chemical analyses and high-resolution surface imaging. The difference tendencies toward protein membrane-surface adhesion for both materials contributed to biological activations when studying in vitro clinical tests with inflammatory biomarkers using Human Magnetic Luminex assays of Serpin/ Antithrombin-III, Properdin, C5a, 1L-1α, 1L-1β, TNF-α, IL6, and vWF. Experimental results have been complemented with Molecular Modeling Docking analyses in the assessment of interaction patterns of human serum proteins in a view to understanding the relationship between functional group chemistry and membrane-surface bonding. Our models reveal inherent binding between PAN nitrogen atoms and protein-bound amino acids while the PES model proposes a contribution with its sulfone chemical groups as a prerequisite to membrane-surface binding resulting in high levels of complement and inflammation factors. The differences in protein adhesion between both clinical membrane modules are attributed to varying degrees of surface hydrophilicity as a direct factor of protein/membrane biocompatibility. Both membranes interacted differently with ALB, FB and TR, however, PAN membrane exhibited less affinity for protein adsorption and membrane-surface fouling.

Poly(2-ethyl-2-oxazoline) functionalized reduced graphene oxide: Optimization of the reduction process using dopamine and application in cancer photothermal therapy

The high near infrared (NIR) absorption displayed by reduced graphene oxide (rGO) nanostructures renders them a great potential for application in cancer photothermal therapy. However, the production of this material often relies on the use of hydrazine as a reductant, leading to poor biocompatibility and environmental-related issues. In addition, to improve rGO colloidal stability, this material has been functionalized with poly(ethylene glycol). However, recent studies have reported the immunogenicity of poly(ethylene glycol)-based coatings. In this work, the production of rGO, by using dopamine as the reducing agent, was optimized considering the size distribution and NIR absorption of the attained materials. The obtained results unveiled that the rGO produced by using a 1:5 graphene oxide:dopamine weight ratio and a reaction time of 4 h (termed as DOPA-rGO) displayed the highest NIR absorption while retaining its nanometric size distribution. Subsequently, the DOPA-rGO was functionalized with thiol-terminated poly(2-ethyl-2-oxazoline) (P-DOPA-rGO), revealing suitable physicochemical features, colloidal stability and cytocompatibility. When irradiated with NIR light, the P-DOPA-rGO could produce a temperature increase (ΔT) of 36 °C (75 μg/mL; 808 nm, 1.7 W/cm2, 5 min). The photothermal therapy mediated by P-DOPA-rGO was capable of ablating breast cancer cells monolayers (viability < 3%) and could reduce heterotypic breast cancer spheroids' viability to just 30%. Overall, P-DOPA-rGO holds a great potential for application in breast cancer photothermal therapy.

Biocompatibility assessment of biomaterials used in orthopedic devices: An overview (Review).

Biocompatibility is one of the mandatory requirements for the clinical use of biomaterials in orthopedics. It refers to the ability of a biomaterial to perform its function without eliciting toxic or injurious effects on biological systems but producing an appropriate host response in a specific case. Today, the biocompatibility concept includes not only bio-inertia, but also biofunctionality and biostability. High biocompatibility and functional properties are highly desirable for new biomaterials. The chemical, mechanical, structural properties of biomaterials, their interaction with biological environment or even the methodology of assessment can influence the biocompatibility. The biological evaluation of biomaterials includes a broad spectrum of in vitro and in vivo tests related to the cytocompatibility, genotoxicity, sensitization, irritation, acute and chronic toxicity, hemocompatibility, reproductive and developmental toxicitity, carcinogenicity, implantation and degradation as specified in different international standards. A brief review of the main assays used in the biocompatibility testing of orthopedic biomaterials is presented. In addition, their main biocompatibility issues are overviewed.

Triple-Configurational Magnetic Robot for Targeted Drug Delivery and Sustained Release.

Active targeted therapy for bowel cancer using untethered microrobots has attracted extensive attention. However, traditional microrobots face challenges, such as issues of mobility, biocompatibility, drug loading, sustained-release capabilities, and targeting accuracy. Here, we propose an untethered triple-configurational magnetic robot (TCMR) that is composed of three geometrically nested parts: actuation and guarding, anchoring and seeding, and drug release part. A targeting magnetic driving system actuates the TCMR along the predetermined trajectory to the target position. The pH-sensitive actuation and guarding part formed by electrodeposition is degraded in the intestinal environment and separates from the two other parts. A majority of magnetic nanoparticles encapsulated in this part are retrieved. The anchoring and seeding part anchors the lesion area and seeds the drug release part in the gaps of intestinal villi by hydrolysis. Ultimately, the drug release part containing the therapeutic completes the sustained release to prolong the duration of the therapeutic agent. Cytotoxicity and therapeutic tests reveal that TCMRs are biocompatible and suitable for targeted therapy and have good therapeutic performance. The newly designed TCMR will provide new ideas for targeted therapy, thus expanding the application scope of robotics technology in the biomedical field.

Biocompatibility of 2D silicon nitride: interaction at the nano-bio interface

Determining potential abilities of nanostructures to induce toxicity to biological molecules is still a convoluted challenge in the realm of nanomedicine. Based on the unprecedented achievements of two-dimensional nanomaterials in nearly all areas of applied sciences particularly medicine, we carried out all-atom molecular dynamics simulations to assess the biologically important, yet unmapped issue of biocompatibility of 2D, hexagonal β-Si3N4 nanosheet via investigating its possible cross interactions with both human serum albumin (HSA) and p53 tumor suppressor. Examining the conventional MD indicators in presence and absence of the monolayer revealed that hexagonal Si3N4 nanosheet weakly binds to these two proteins without inducing any important, dramatic change to their secondary structures, revealing accordingly the biological compatibility of the monolayer in case it is released as therapeutics or carriers in vivo. This finding was also broadly supported by the related time-dependent behaviors of the protein-monolayer as well as the protein-water interaction energies.

Overview on the Antimicrobial Activity and Biocompatibility of Sputtered Carbon-Based Coatings

Due to their outstanding properties, carbon-based structures have received much attention from the scientific community. Their applications are diverse and include use in coatings on self-lubricating systems for anti-wear situations, thin films deposited on prosthetic elements, catalysis structures, or water remediation devices. From these applications, the ones that require the most careful testing and improvement are biomedical applications. The biocompatibility and antibacterial issues of medical devices remain a concern, as several prostheses still fail after several years of implantation and biofilm formation remains a real risk to the success of a device. Sputtered deposition prevents the introduction of hazardous chemical elements during the preparation of coatings, and this technique is environmentally friendly. In addition, the mechanical properties of C-based coatings are remarkable. In this paper, the latest advances in sputtering methods and biocompatibility and antibacterial action for diamond-based carbon (DLC)-based coatings are reviewed and the greater outlook is then discussed.

Review of Various Hydroxyapatite Coating Methods on SS316L Foam for Biomedical Application

Metallic biomaterials such as 316L stainless steel (SS316L) are widely used as an implant to replace the function of damaged bone, especially in hip or knee applications. However, many of them fail during a short period or have complications. The biocompatibility issues are the main factor that caused this failure. Thus, coating the SS316L with bioactive and biocompatible material is one of the promising techniques to enhance the biocompatibility and lifetime of the implant. This paper provides an overview of the SS316L foam coated hydroxyapatite (HA). Various methods of HA coating such as sol-gel, dip coating, electrophoretic deposition, plasma spraying, and pulse laser deposition applied on SS316L foam and their coating characteristics were investigated based on recent literature. SS316L foam coated HA using different coating methods were compiled and their basic properties were reported. Therefore, this paper will benefit future works on SS316L foam coated HA in a biomedical application.

Low‐frequency nanocomposite piezoelectric energy harvester with embedded zinc oxide nanowires

AbstractSweeping developments in microelectromechanical systems and low power electronics have pushed the need for piezoelectric energy harvesters (PEHs). Increasing environmental and biocompatibility issues have drawn interest in lead‐free piezoelectric materials. In this paper, cantilever‐type PEHs at centimeter scale have been proposed to harvest the energies of low‐frequency vibrations caused by a human's movements. The proposed PEHs are made of a passive PDMS substrate sandwiched between two active nanocomposite layers with embedded piezoelectric zinc oxide (ZnO) nanowires. Moreover, two different morphologies including PEHs with constant and tapered thicknesses have been considered. The material properties of such piezoelectric nanocomposites are calculated by an electromechanical model. Afterward, these novel PEHs have been developed in COMSOL Multiphysics and their static and dynamic performances have been investigated. The static study shows that tapered PEHs endures lower stresses. However, the dynamic study discloses that the rectangular design outperforms the tapered one in electrical power and resonance frequency. It is found that the rectangular design can produce 4.1623 μW at the resonant frequency of 25.8 Hz.

Toward living neuroprosthetics: developing a biological brain pacemaker as a living neuromodulatory implant for improving parkinsonian symptoms

Objective. Therapeutic intervention for Parkinson’s disease (PD) via deep brain stimulation (DBS) represents the current paradigm for managing the advanced stages of the disease in patients when treatment with pharmaceuticals becomes inadequate. Although DBS is the prevailing therapy in these cases, the overall effectiveness and reliability of DBS can be diminished over time due to hardware complications and biocompatibility issues with the electronic implants. To achieve a lifetime solution, we envision that the next generation of neural implants will be entirely ‘biological’ and ‘autologous’, both physically and functionally. Thus, in this study, we set forth toward developing a biological brain pacemaker for treating PD. Our focus is to investigate engineering strategies for creating a multicellular biological circuit that integrates innate biological design and function while incorporating principles of neuromodulation to create a biological mechanism for delivering high-frequency stimulation with cellular specificity. Approach. We engineer a 3D multicellular circuit design built entirely from biological and biocompatible components using established tissue engineering protocols to demonstrate the feasibility of creating a living neural implant. Furthermore, using 2D co-culture systems, we investigate the physiologically relevant parameters that would be necessary to further develop a therapeutic benefit of high-frequency stimulation with cellular specificity within our construct design. Main results. Our results demonstrate the feasibility of fabricating a 3D multicellular circuit device in an implantable form. Furthermore, we show we can organize cellular materials to create potential functional connections in normal physiological conditions, thus laying down the foundation of designing a high-frequency pacing system for selective and controlled therapeutic neurostimulation. Significance. The findings from this study may lead to the future development of autologous living neural implants that both circumvent the issues inherent in electronic neural implants and form more biocompatible devices with lifelong robustness to repair and restore motor functions, with the ultimate benefit for patients with PD.

(Invited) Bioelectronic Modulation with Soft-Hard Composites

Biointerface devices can probe fundamental biological dynamics and improve the lives of human beings. However, the direct application of traditional rigid electronics onto soft tissues or cells can cause signal transduction and biocompatibility issues, due to mechanical mismatch at the biointerfaces. One common mitigation strategy is the use of nanostructures or soft-hard composites to form more biocompatible interfaces with target cells or tissues. My group integrates nanoscience and soft matter physics with biophysics to study several semiconductor- or conductor-based biointerfaces. In this talk, I will first pinpoint domains where semiconductor properties can be leveraged for biointerface studies. Next, I will present a few recent studies from our lab and highlight key bioelectrical mechanisms underlying the non-genetic optical or electrochemical modulation interfaces. The non-genetic and soft-hard composite-based methods have the potential to overcome the limitations of current metal electrode-based devices such as bulk and cell membrane disruption, and are not dependent on genetic modifications. Finally, I will discuss new tissue-like materials and other biological targets that could catalyze future advances.

Innate Immune Invisible Ultrasmall Gold Nanoparticles-Framework for Synthesis and Evaluation.

Nanomedicine is seen as a potential central player in the delivery of personalized medicine. Biocompatibility issues of nanoparticles have largely been resolved over the past decade. Despite their tremendous progress, less than 1% of applied nanosystems can hit their intended target location, such as a solid tumor, and this remains an obstacle to their full ability and potential with a high translational value. Therefore, achieving immune-tolerable, blood-compatible, and biofriendly nanoparticles remains an unmet need. The translational success of nanoformulations from bench to bedside involves a thorough assessment of their design, compatibility beyond cytotoxicity such as immune toxicity, blood compatibility, and immune-mediated destruction/rejection/clearance profile. Here, we report a one-pot process-engineered synthesis of ultrasmall gold nanoparticles (uGNPs) suitable for better body and renal clearance delivery of their payloads. We have obtained uGNP sizes of as low as 3 nm and have engineered the synthesis to allow them to be accurately sized (almost nanometer by nanometer). The synthesized uGNPs are biocompatible and can easily be functionalized to carry drugs, peptides, antibodies, and other therapeutic molecules. We have performed in vitro cell viability assays, immunotoxicity assays, inflammatory cytokine analysis, a complement activation study, and blood coagulation studies with the uGNPs to confirm their safety. These can help to set up a long-term safety-benefit framework of experimentation to reveal whether any designed nanoparticles are immune-tolerable and can be used as payload carriers for next-generation vaccines, chemotherapeutic drugs, and theranostic agents with better body clearance ability and deep tissue penetration.

Twin Nanopipettes for Real-Time Electrochemical Monitoring of Cytoplasmic Microviscosity at a Single-Cell Level.

Cytoplasmic microviscosity (CPMV) plays essential roles in governing the diffusion-mediated cellular processes and has been recognized as a reliable indicator of the cellular response of many diseases and malfunctions. Current CPMV studies are exclusively established by probe-assisted optical methods, which nevertheless necessitate the complicated synthesis and delivery of optical probes into cells and thus the issues of biocompatibility and bio-orthogonality. Using twin nanopipettes integrated with a patch-clamp system, a practical electrochemical single-cell measurement is presented, which is capable of real-time and long-term CPMV detection without cell disruption. Specifically, upon the operation of the twin nanopipettes, the cellular CPMV status, which is correlated to cytoplasmic ionic mobility, could be sensibly transduced via the ionic current passing through the nanosystem. The average CPMV value of HeLa cells was detected as ca. 86 cP. Notably, the correlation between chemotherapy and CPMV alterations makes this approach possible for the real-time and long-term assessment of the evolution of external stimuli, as exemplified by the two natural products taxol and colchicine. Integrated with the patch-clamp setup, this study features the first use of twin nanopipettes for electrochemical CPMV monitoring of single living cells, and it is expected to inspire more interest in the exploitation of dual- and multiple nanopipettes for advanced single-cell analysis.

An in-vivo study to evaluate and compare the effect of three different zinc free denture adhesives on retention of mandibular complete dentures after different adaptation periods

Retention in mandibular dentures has always been a challenge for the Prosthodontist and this situation worsens in patients with resorbed ridges. Denture adhesives are known to improve the adhesive bond between the denture and the underlying tissues. But still biocompatibility issues have been noticed from zinc containing denture adhesives in various studies and they recommended using zinc free denture adhesives. However, zinc free denture adhesives still remain unexplored and not much is known about the efficacy of these materials in mandibular dentures especially in patients with poor foundations. The present study was carried out to compare the efficacy of three different commercially available zinc free denture adhesives in relation to their retentive ability in patients with well formed mandibular ridges and in patients with resorbed mandibular ridges. Thirty edentulous patients were selected and the patients were divided into 2 groups; group A comprised of 15 patients with well formed mandibular ridges and group B consisted of 15 patients having resorbed mandibular ridges. The adhesion and cohesion that developed between the dentures and the underlying tissues with and without denture adhesives was evaluated with the help of a force gauge test apparatus in newtons at three different times of adaptation period. Zinc free denture adhesives significantly improved the retention of mandibular complete dentures not only in case of well-formed residual ridges but also resorbed ridges. Use of zinc free denture adhesive led to a higher value of retention as opposed to when the dentures were used without adhesives at all time intervals of adaptation period. Poligrip adhesive was the most effective among all three adhesives used in the study, while Secure was intermediate and Fixon Supergrip was least effective.

Implantable Biosupercapacitor Inspired by the Cellular Redox System

AbstractThe carbon nanotube (CNT) yarn supercapacitor has high potential for in vivo energy storage because it can be used in aqueous environments and stitched to inner parts of the body, such as blood vessels. The biocompatibility issue for frequently used pseudocapacitive materials, such as metal oxides, is controversial in the human body. Here, we report an implantable CNT yarn supercapacitor inspired by the cellular redox system. In all living cells, nicotinamide adenine dinucleotide (NAD) is a key redox biomolecule responsible for cellular energy transduction to produce adenosine triphosphate (ATP). Based on this redox system, CNT yarn electrodes were fabricated by inserting a twist in CNT sheets with electrochemically deposited NAD and benzoquinone for redox shuttling. Consequently, the NAD/BQ/CNT yarn electrodes exhibited the maximum area capacitance (55.73 mF cm−2) under physiological conditions, such as phosphate‐buffered saline and serum. In addition, the yarn electrodes showed a negligible loss of capacitance after 10 000 repeated charge/discharge cycles and deformation tests (bending/knotting). More importantly, NAD/BQ/CNT yarn electrodes implanted into the abdominal cavity of a rat's skin exhibited the stable in vivo electrical performance of a supercapacitor. Therefore, these findings demonstrate a redox biomolecule‐applied platform for implantable energy storage devices.

Engineering motile aqueous phase-separated droplets via liposome stabilisation

There are increasing efforts to engineer functional compartments that mimic cellular behaviours from the bottom-up. One behaviour that is receiving particular attention is motility, due to its biotechnological potential and ubiquity in living systems. Many existing platforms make use of the Marangoni effect to achieve motion in water/oil (w/o) droplet systems. However, most of these systems are unsuitable for biological applications due to biocompatibility issues caused by the presence of oil phases. Here we report a biocompatible all aqueous (w/w) PEG/dextran Pickering-like emulsion system consisting of liposome-stabilised cell-sized droplets, where the stability can be easily tuned by adjusting liposome composition and concentration. We demonstrate that the compartments are capable of negative chemotaxis: these droplets can respond to a PEG/dextran polymer gradient through directional motion down to the gradient. The biocompatibility, motility and partitioning abilities of this droplet system offers new directions to pursue research in motion-related biological processes.

Inversion in usual excitation intensities from solid state phosphor and improved fluorescence of Eu3+ ion in type (IV) deep eutectic solvent

To resolve the issue of aggregation induced quenching (AIQ), poor adhesion/dispersion on film and fiber, limited dispersability/solubility and non biocompatibility issue; phosphor powder particles are generally casted into solution form. It was found in most cases that lanthanide luminescence and lifetime reduced substantially in aqueous medium and ionic liquid. Deep eutectic solvent (DES) has been found to be an alternate and more efficient solvent for lanthanide luminescence. With similar intention we have synthesized europium type (IV) DES (EuDES) via mechanochemical synthesis employing europium nitrate and urea. Fourier transformed infrared spectroscopy (FTIR) studies confirms that in DES, the Eu3+ ion is surrounded by bidentate nitrate ions and urea is coordinated to europium centre by CO group. There is no water molecule in primary coordination sphere of Eu3+ ion. Interestingly with rigid H-bonding and strong chemical interaction offered by DES; Eu3+ CTB is quenched whereas very high intensity of Eu3+ intra f-f transition appears which was reversal from usual trend. Moreover asymmetry ratio was found to be more than 3 with predominantly high intensity of electric dipole transition (EDT) suggesting very asymmetric environment around Eu3+ in DES. But the distribution of europium was found to be very homogenous with luminescence lifetime of ~3.7 ms and point group symmetry ~ C6v. Judd-Ofelt analysis suggested very low non-radiative channels present in DES resulting in extremely high quantum yield ~76% and very high color purity of 94.72% which was also assisted by absence of any water molecule as suggested by FTIR measurement.

Mechanical and microstructural characterization of bio-concrete prepared with optimized alternative green binders

Due to their high alkaline natrure, ordinary Portland cement and lime based traditional binders show poor compatibility with the bio-aggregates. As a results, produced bio-concretes show prolonged setting time, poor mechanical and durability properties. In order to use the traditional binders in preparing the bio-concrete, the use of expensive treatment methods to improve bio-comptability of these binders become inevitable. In this regards, this research aims to solve the bio-compatibility issues of traditional binders and develop new green binders to prepare bio-concrete. In the first part, mechanical and chemical characterization (through XRD, DTG/TGA and SEM) of Portland cement (OPC), geopolymer (GP) and magnesium phosphate cement (MPC) binders was carried out. Optimized binders from each group were then further used to produce bio-concretes. In the second part, influence of type of binder and pretreament on the properties of bio-concrete was examined. It was observed that hydrophobic treatment was most efficient and increased the amount of hydration products (studied through XRD, FTIR and SEM) and bio-compatibility of OPC and GP binders. However, MPC binder was naturally compatible with the bio-aggregates due to its low pH value and do not necessarily demand any pretreatment of bio-aggregate. It was concluded that, MPC based bio-concrete shows high performance as compared to OPC and GP based bio-concrete.

Low-cost microfluidic device micromachining and sequential integration with SAW sensor intended for biomedical applications

The paper reports on fabrication processes related to low-cost manufacturing and integration of microfluidic biomedical detection systems fabricated without a cleanroom. First, we developed and demonstrated a process for manufacturing a microfluidic device. Second, we demonstrated a low temperature assembly technique for the packaging of the surface acoustic wave (SAW) sensor die. Sequentially, we demonstrated a low temperature process for the integration of the microfluidic device with a SAW sensor to form a fully functional biomedical detection system. The microfluidic device was manufactured by mechanical micromilling technology that is rapid, conceptually simple and a low-cost process. It is suitable for both prototyping and for a low and a medium scale production to address a niche market that is typical for the intended application. That technology has no specific requirement for a certified clean room environment. Unlikely other technology, such as molding and photolithography, for example, it has a shorter lead-time from design to manufacturing. The assembly technique for a SAW sensor is a carefully selected combination of known and matured processing steps causing no damage to a sensitive biofunctionalization on the sensor. The developed and demonstrated integration process for the in-house manufactured microfluidic device and the SAW sensor is a purely low temperature process that prevents a biological material deposited on the SAW sensor from degradation. Biocompatibility issues were also addressed during the study reported. Finally, we performed an ultrasonic (US) impedance characterization of the fully assembled system and demonstrated that neither the microfluidic system integrated on the sensor nor the integration process itself have an impact on the US impedance of the SAW sensor. That means that it does not affect the sensor performance.

3D Printing for Hip Implant Applications: A Review.

There is a rising demand for replacement, regeneration of tissues and organ repairs for patients who suffer from diseased/damaged bones or tissues such as hip pains. The hip replacement treatment relies on the implant, which may not always meet the requirements due to mechanical and biocompatibility issues which in turn may aggravate the pain. To surpass these limitations, researchers are investigating the use of scaffolds as another approach for implants. Three-dimensional (3D) printing offers significant potential as an efficient fabrication technique on personalized organs as it is capable of biomimicking the intricate designs found in nature. In this review, the determining factors for hip replacement and the different fabrication techniques such as direct 3D printing, Fused Deposition Modelling (FDM), Selective Laser Sintering (SLS) and stereolithography (SLA) for hip replacement. The study also covers surface modifications of 3D printed implants and provides an overview on 3D tissue regeneration. To appreciate the current conventional hip replacement practices, the conventional metallic and ceramic materials are covered, highlighting their rationale as the material of choice. Next, the challenges, ethics and trends in the implants’ 3D printing are covered and conclusions drawn. The outlook and challenges are also presented here. The knowledge from this review indicates that 3D printing has enormous potential for providing a pathway for a sustainable hip replacement.

A novel suprachoroidal microinvasive glaucoma implant: in vivo biocompatibility and biointegration

BackgroundA major challenge for any glaucoma implant is their ability to provide long-term intraocular pressure lowering efficacy. The formation of a low-permeability fibrous capsule around the device often leads to obstructed drainage channels, which may impair the drainage function of devices. These foreign body-related limitations point to the need to develop biologically inert biomaterials to improve performance in reaching long-term intraocular pressure reduction. The aim of this study was to evaluate in vivo (in rabbits) the ocular biocompatibility and tissue integration of a novel suprachoroidal microinvasive glaucoma implant, MINIject™ (iSTAR Medical, Wavre, Belgium).ResultsIn two rabbit studies, no biocompatibility issue was induced by the suprachoroidal, ab-externo implantation of the MINIject™ device. Clinical evaluation throughout the 6 post-operative months between the sham and test groups were similar, suggesting most reactions were related to the ab-externo surgical technique used for rabbits, rather than the implant material itself. Histological analysis of ocular tissues at post-operative months 1, 3 and 6 revealed that the implant was well-tolerated and induced only minimal fibroplasia and thus minimal encapsulation around the implant. The microporous structure of the device became rapidly colonized by cells, mostly by macrophages through cell migration, which do not, by their nature, impede the flow of aqueous humor through the device. Time-course analysis showed that once established, pore colonization was stable over time. No fibrosis nor dense connective tissue development were observed within any implant at any time point. The presence of pore colonization may be the process by which encapsulation around the implant is minimized, thus preserving the permeability of the surrounding tissues. No degradation nor structural changes of the implant occurred during the course of both studies.ConclusionsThe novel MINIject™ microinvasive glaucoma implant was well-tolerated in ocular tissues of rabbits, with observance of biointegration, and no biocompatibility issues. Minimal fibrous encapsulation and stable cellular pore colonization provided evidence of preserved drainage properties over time, suggesting that the implant may produce a long-term ability to enhance aqueous outflow.