Biomaterial Interface Research Articles

The Functional Role of Interface Tissue Engineering in Annulus Fibrosus Repair: Bridging Mechanisms of Hydrogel Integration with Regenerative Outcomes.

Hydrogels are extraordinarily versatile by design and can enhance repair in diseased and injured musculoskeletal tissues. Biological fixation of these constructs is a significant determinant factor that is critical to the clinical success and functionality of regenerative technologies for musculoskeletal repair. In the context of an intervertebral disc (IVD) herniation, nucleus pulposus tissue protrudes through the ruptured annulus fibrosus (AF), consequentially impinging on spinal nerve roots and causing debilitating pain. Discectomy is the surgical standard of care to treat symptomatic herniation; however these procedures do not repair AF defects, and these lesions are a significant risk factor for recurrent herniation. Advances in tissue engineering utilize adhesive hydrogels as AF sealants; however these repair strategies have yet to progress beyond preclinical animal models because these biomaterials are often plagued by poor integration with AF tissue and lead to large variability in repair outcomes. These critical barriers to translation motivate this article to review the material composition of hydrogels that have been evaluated in situ for AF repair, proposed mechanisms of how these biomaterials interface with AF tissue, and their functional outcomes after treatment in order to inform the development of new hydrogels for AF repair. In this systematic review, we identify 18 hydrogel formulations evaluated for AF repair, all of which demonstrate large heterogeneity in their interfacing mechanisms and reported outcome measures to assess the effectiveness of repair. Hydrogels that covalently bond to AF tissue were found to be the most successful in improving IVD biomechanical properties from the injured state, but none were able to restore properties to the intact state suggesting that new repair strategies with innovative surface chemistries are an important future direction. We additionally review biomechanical evaluation methods and recommend standardization in the field of AF tissue engineering to establish mechanical benchmarks for translation and ensure clinical feasibility.

Biomimetic fabrication of dynamic biointerfaces with optional and diversified bioactivities through reversible covalent and bioorthogonal chemistry

As extracellular matrix (ECM) mimics, dynamic biointerfaces with reversible ligand presentation have shown great significance in the field of biology and medicine. However, current systems are trapped in the monotony of bioactivity, which makes it hard to mimic the multipotential of natural ECM. In this work, we reported a dynamic biomaterial interface with optional and diversified bioactivities by the combination of reversible catechol-boronate and bioorthogonal click chemistry. Due to the specificity and thoroughness of bioorthogonal reaction, different types of biomolecules including small molecular saccharide, macromolecular peptides and DNA aptamers could be on-demand and reversible binding on biomaterial interfaces through sugar-sensitive catechol-boronate interactions. In this design, the obtained dynamic biointerface showed biocompatible sugar-responsiveness and enabled reversible presentation of diversified bioactivities, exhibiting the multipotential to manipulate a variety of cell-biomaterial interactions. Cell capture/release experiments confirmed our dynamic biointerface could reversibly and selectively bind different cancer cells and even the bacterial microorganism. In short, apart from the original significance in ECM mimicking, the optional and diversified bioactivities on our developed dynamic biointerface will also show promising prospects in biomedical science, in particular, the cell isolation area for diagnostics and therapeutics.

An Investigation on the Crustal Velocity Variations of the North Anatolian Fault Zone by a Dense Seismic Array

Aktif fay zonları boyunca asimetrik olarak dağılmış olan mikro çatlaklar bu zonlardaki depremlerin tekrarlı oluşumları nedeniyle meydana gelmektedir. Aynı bölgede sürekli tekrarlanan depremler, elastik olarak farklı olan malzemeleri ayırarak iki-malzemeli arayüzeyler meydana getirir ve deprem davranışını etkileyen önemli sonuçlar doğurur. Kuzey Anadolu Fay Zonu üzerinde kurulan DANA (Dense Array of Northern Anatolia) sismik ağı Kuzey Anadolu Fay Zonu’nun Sakarya ve Sapanca segmentleri üzerinde iki malzemeli arayüzeyin incelenmesi için elverişli veri sağlamaktadır. Bu çalışmanın amacı, yoğun sismik dizilim bulunan Kuzey Anadolu Fay Zonu’nun (KAFZ) batı ucunda Sakarya ve Sapanca segmentleri arasında, deprem dalgası çapraz ilişki analizleri kullanarak, iki malzemeli arayüzey geçişindeki hız değişimlerini belirlemektir. Araştırma kapsamında 2012-2013 yıllarında, çalışma alanında faaliyet gösteren DANA geçici sismik ağına ait 73 adet sismik istasyondan, 109 adet uzak deprem kaydı kullanılarak 50.000'den fazla dalga formu derlenmiştir. Uzak deprem dalgalarının, sismik kayıtçılara varışları arasındaki zaman farkları, fayın karşılıklı bölümlerinde kabuktaki hız kontrastını tespit etmek ve fark değerini ölçmek için kullanılmıştır. Elde edilen bulgular KAFZ kuzey kolunun kuzeybatısında düşük, kollar arası Armutlu-Ovacık bloğu altında yüksek hızlara işaret etmektedir. Referans kayıtçıların analizinde, hız oranlarında lokal değişimler hesaplanmış olsa da, bölge geneline bakıldığında KAFZ kuzey kolunun kuzeyi ile, yine KAFZ kuzey kolunun doğusu ve güney doğusu arasında görece büyük hız farkları elde edilmiştir. Sonuçlar, KAFZ kuzey ve güney kollarındaki hız değişimlerini ve genel tektonik ortamla ilişkilendirilen özellikleri ortaya koymaktadır.

Development of a conductive biocomposite combining graphene and amniotic membrane for replacement of the neuronal network of tissue-engineered urinary bladder

Tissue engineering allows to combine biomaterials and seeded cells to experimentally replace urinary bladder wall. The normal bladder wall however, includes branched neuronal network propagating signals which regulate urine storage and voiding. In this study we introduced a novel biocomposite built from amniotic membrane (Am) and graphene which created interface between cells and external stimuli replacing neuronal network. Graphene layers were transferred without modifying Am surface. Applied method allowed to preserve the unique bioactive characteristic of Am. Tissue engineered constructs composed from biocomposite seeded with smooth muscle cells (SMC) derived from porcine detrusor and porcine urothelial cells (UC) were used to evaluate properties of developed biomaterial. The presence of graphene layer significantly increased electrical conductivity of biocomposite. UCs and SMCs showed an organized growth pattern on graphene covered surfaces. Electrical filed stimulation (EFS) applied in vitro led additionally to increased SMCs growth and linear arrangement. 3D printed chamber equipped with 3D printed graphene based electrodes was fabricated to deliver EFS and record pressure changes caused by contracting SMCs seeded biocomposite. Observed contractile response indicated on effective SMCs stimulation mediated by graphene layer which constituted efficient cell to biomaterial interface.

The Construction and Application of Three-Dimensional Biomaterials.

Biomaterials have been widely explored and applied in many areas, especially in the field of tissue engineering. The interface of biomaterials and cells has been deeply investigated. However, it has been demonstrated that conventional 2D biomaterials fail to maintain the 3D structures and phenotypes of cells, which is the result of their limited ability to mimic the latter's complex extracellular matrix. To overcome this challenge, cell cultivation dependent on 3D biomaterials has emerged as an alternative strategy to make the recovery of 3D structures and functions of cells possible. Thus, with the thriving development of 3D cell culture in tissue engineering, a holistic review of the construction and application of 3D biomaterials is desired. Here, recent developments in 3D biomaterials for tissue engineering are reviewed. An overview of various approaches to construct 3D biomaterials, such as electro-jetting/-spinning, micro-molding, microfluidics, and 3D bio-printing, is first presented. Their typical applications in constructing cell sheets, vascular structures, cell spheroids, and macroscopic cellular constructs are described as well. Following these two sections, the current status and challenges are analyzed, as well as the future outlook of 3D biomaterials for tissue engineering.

Advancing photosystem II photoelectrochemistry for semi-artificial photosynthesis

Oxygenic photosynthesis is the primary solar energy-conversion process that supports much of life on Earth. It is initiated by photosystem II (PSII), an enzyme that extracts electrons from H2O and feeds them into an electron-transport chain to result in chemical synthesis using the input of solar energy. PSII can be immobilized onto electrodes for photoelectrochemical studies, in which electrons photogenerated from PSII are harnessed for enzyme characterization, and to drive fuel-forming reactions by electrochemically coupling the PSII to a suitable (bio)catalyst. Research in PSII photoelectrochemistry has recently made substantial strides in electrode design and unravelling charge-transfer pathways at the bio–material interface. In turn, these efforts have opened up possibilities in the field of bio-photoelectrochemistry, expanding the range of biocatalysts that can be systematically interrogated, including biofilms of whole photosynthetic cells. Furthermore, these studies have accelerated the development of semi-artificial photosynthesis to afford autonomous, solar-driven, fuel-forming biohybrid devices. This Review summarizes the latest advancements in PSII photoelectrochemistry with respect to electrode design and understanding of the bio-material interface, on both the protein and cellular level. We also discuss the role of biological photosynthetic systems in present and future semi-artificial photosynthesis. A light-driven enzyme that oxidizes H2O, photosystem II has inspired a wealth of solar fuels research and is used directly in semi-artificial photosynthesis. This Review describes the photosystem–electrode interface, as well as state-of-the-art electrode and biohybrid cell designs, and their importance in bio-photoelectrochemistry and semi-artificial photosynthesis.

A glance on the role of fibronectin in controlling cell response at biomaterial interface.

SummaryThe bioactivity of biomaterials is closely related to cell response in contact with them. However, shortly after their insertion, materials are soon covered with proteins that constitute the biological fluids, and which render the direct surface recognition by cells almost impossible. The control of protein adsorption at the interface is therefore desirable. Extracellular matrix proteins are of particular interest in this sense, due to their well-known ability to modulate cell behavior. Particularly, fibronectin plays a leading role, being present in both healthy and injured tissues undergoing healing and regeneration. The aim of the present work is to give an overview on fibronectin and on its involvement in the control of cell behavior providing evidence of its pivotal role in the control of cell adhesion, spreading, migration, proliferation and differentiation. A deep insight into methods to enrich biomaterials surface with fibronectin will be then discussed, as well as new cues on the possibility to design tailored platforms able to specifically retain fibronectin from the surrounding extracellular milieu.

Exploration of Chitinous Scaffold-Based Interfaces for Glucose Sensing Assemblies.

The nanomaterial-integrated chitinous polymers have promoted the technological advancements in personal health care apparatus, particularly for enzyme-based devices like the glucometer. Chitin and chitosan, being natural biopolymers, have attracted great attention in the field of biocatalysts engineering. Their remarkable tunable properties have been explored for enhancing enzyme performance and biosensor advancements. Currently, incorporation of nanomaterials in chitin and chitosan-based biosensors are also widely exploited for enzyme stability and interference-free detection. Therefore, in this review, we focus on various innovative multi-faceted strategies used for the fabrication of biological assemblies using chitinous biomaterial interface. We aim to summarize the current development on chitin/chitosan and their nano-architecture scaffolds for interdisciplinary biosensor research, especially for analytes like glucose. This review article will be useful for understanding the overall multifunctional aspects and progress of chitin and chitosan-based polysaccharides in the food, biomedical, pharmaceutical, environmental, and other diverse applications.

Glutathione-Sensitive Silicon Nanowire Arrays for Gene Transfection.

Ingenious surface modification strategies and special topological morphologies endow the biomaterial interface with excellent ability to regulate the cell fate. In this work, a gene delivery platform based on glutathione-sensitive silicon nanowire arrays (SiNWAs) is developed, exhibiting good transfection efficiency of several cell types. Briefly, the surface of SiNWAs is grafted of PEICBA, a branched cationic polymer cross-linked by disulfide bonds (SN-PEICBA). When the cells adhere to the platform surface, silicon nanowires penetrate into the cells and the high concentration of reduced glutathione (GSH) in cytoplasm breaks the disulfide bonds (S-S) in PEICBA. The plasmid DNA preloaded on the cationic polymers is successfully delivered to the nuclei through the nonlysosomal pathway. Cells harvested from the SN-PEICBA show high retention of viability and the platform surface can be reused though S-S replacement for at least three times. In general, our platform is a creative combination of intracellular responsive strategy and surface morphology, which has great potential for auxiliary use in ex vivo cell-based therapies and various biomedical applications.

Optimization of specific cell-peptide interactions at the bio-material interface via regulation of nonspecific biofouling interactions

Optimization of specific cell-peptide interactions at the bio-material interface via regulation of nonspecific biofouling interactions

Fabrication and preliminary evaluation of the osteogenic potential for micro-/nano-structured porous BCP ceramics

Nanoscale interface of biomaterials exhibits superiorities in promoting tissue repair and healing. Bioceramics are one of the most commonly used biomaterials for biological purposes such as tissue engineering. The fabrication of nanoscale ceramics with smart topography is essential for modulating cells in contact with such surface. In this research, a gas foaming method was employed to fabricate porous biphasic calcium phosphate (BCP) ceramics as substrates with a controllable component of hydroxyapatite/beta tricalcium phosphate (HA/β-TCP). Hydrothermal reaction was then introduced to modify the surface morphology of the substrates to obtain a nanoscale topography at different pH values and ionic microenvironments. Three kinds of ceramics (BCP; BCP with a nanoneedle-like surface, BNN; BCP covered with a hollow nanorod-like surface, BHN) were prepared with different surface morphologies and roughness, degradation properties and the phase composition during the hydrothermal process. All of them possessed an interconnected pore structure of macropores and micropores. Importantly, the nano-scale surface structure increased the total pore volumes as well as the micropore volumes, thus enhanced the specific surface area (SSA) and subsequent biological performance. Their biological behavior has also been assessed through a series of pivotal events, i.e. protein adsorption, cell attachment, proliferation, and osteogenic differentiation. Consequently, we found the nano-crystallization of the hollow nanorod-like structured and nanoneedle-like structured ceramic surface enhance the adsorption of both total serum proteins and BSA in vitro compared to the original BCP ceramics with micro-sized grains, as well as exhibit a more persistent release of BSA. Additionally, all the three ceramics have displayed excellent biocompatibilities for MSCs, and the morphology of ceramics played a decisive role in cells spreading and morphology, in which BNN showed the strongest effect to facilitate MSCs differentiation towards osteogenesis.

Poly-l-arginine modifications alter the organization and secretion of collagen in SKH1-E mice.

Functionalized biomaterials interface with tissue upon implantation. There is a growing need to understand how materials properties influence this interaction so that efficient tissue engineering systems can be developed. In this study, we characterize collagen organization in response to functionalized glass beads implanted in SKH1-E mice. Poly-l-arginine (PLR) was modified with arginine derivatives to create a functionalized surface and was coated on glass beads. Tissue sections were removed 28 days post-implantation and were imaged using second harmonic generation (SHG) microscopy. These chemical modifications were able to alter the collagen distribution from highly aligned to disordered (17 ± 6 to 78 ± 1° full width at half-maximum (FWHM)) and the collagen III/I ratio (0.02 to 0.42). Principal component analysis (PCA) comparing the physical properties of the modifiers (e.g. hydrophobicity, molar volume, freely rotating bonds, polarizability) with the SHG analytically derived parameters (e.g. collagen III/I ratio, collagen orientation) was performed. Chemical properties of the PLR-like modifications including lipophilicity, along with the number of freely rotating bonds and the polarizability had significant effects on the collagen surrounding the implant, both in terms of collagen orientation as well as the production of collagen III. These findings demonstrate the possibility of tuning the foreign body response, in terms of collagen deposition and organization, to positively influence the acceptance of implanted biomaterials.

Off-Stoichiometric Reactions at the Cell-Substrate Biomolecular Interface of Biomaterials: In Situ and Ex Situ Monitoring of Cell Proliferation, Differentiation, and Bone Tissue Formation.

The availability of osteoinductive biomaterials has encouraged new therapies in bone regeneration and has potentially triggered paradigmatic shifts in the development of new implants in orthopedics and dentistry. Among several available synthetic biomaterials, bioceramics have gained attention for their ability to induce mesenchymal cell differentiation and successive bone formation when implanted in the human body. However, there is currently a lack of understanding regarding the fundamental biochemical mechanisms by which these materials can induce bone formation. Phenomenological studies of retrievals have clarified the final effect of bone formation, but have left the chemical interactions at the cell–material interface uncharted. Accordingly, the knowledge of the intrinsic material properties relevant for osteoblastogenesis and osteoinduction remains incomplete. Here, we systematically monitored in vitro the chemistry of mesenchymal cell metabolism and the ionic exchanges during osteoblastogenesis on selected substrates through conventional biological assays as well as via in situ and ex situ spectroscopic techniques. Accordingly, the chemical behavior of different bioceramic substrates during their interactions with mesenchymal cells could be unfolded and compared with that of biomedical titanium alloy. Our goal was to clarify the cascade of chemical equations behind the biological processes that govern osteoblastogenic effects on different biomaterial substrates.

(Invited) The Photoelectrochemistry of Photosynthetic Machineries: From Isolated Proteins to Living Cells

The photoelectrochemistry of natural photosynthetic machineries forms the foundations of many upcoming biotechnologies, whilst also providing valuable insights into the bioenergetics of the complex biological systems. Here, I will show recent developments in the integration of cyanobacterial components, including isolated photosystems, thylakoids and live biofilms into inverse opal mesoporous electrodes for photoelectrochemical studies. The systematic comparison of the different components, each being one step removed in metabolic complexity, allows the electron transfer processes at each level to be more effectively teased out. I will also showcase the coupling of photoelectrochemistry with additional biophysical techniques, including quartz crystal microbalance and dissipation, ATR-IR spectroscopy, fluorescence microscopy, and rotating ring disk electrode, for providing complemental insights into the bio-material interface.

Stability of PMMA-grafted/Ti hybrid biomaterial interface in corrosive media

Abstract The stability of interfaces between polymethyl methacrylate (PMMA) and titanium (Ti) are tested in a Ringer solution that is an aggressive medium usually used for biomaterial evaluation. The devices are PMMA-grafted/Ti elaborated via a “grafting-from” method involving three steps, the alkali activation of Ti sheets, their functionalization with an initiator of polymerization through a phosphonate anchoring group and the growth of PMMA brushes. Electrochemical characterizations demonstrate that the stability of the PMMA-grafted/Ti interface in biological medium is satisfactory and that the grafting of PMMA is even acting as a protective barrier for titanium. Indeed, PMMA-grafted/Ti remains passive in Ringer solution until at least +3 V/SCE (saturated calomel electrode), even under inflammatory conditions, while localized corrosion was measured on as-received titanium in similar conditions. This protecting role is attributed to the grafted interface, since spin-coated PMMA does not decrease the corrosion sensitivity of titanium.

Silk fibroin-poly(lactic acid) biocomposites: Effect of protein-synthetic polymer interactions and miscibility on material properties and biological responses.

A protein-polymer blend system based on silkworm silk fibroin (SF) and polylactic acid (PLA) was systematically investigated to understand the interaction and miscibility of proteins and synthetic biocompatible polymers in the macro- and micro-meter scales, which can dramatically control the cell responses and enzyme biodegradation on the biomaterial interface. Silk fibroin, a semicrystalline protein with beta-sheet crystals, provides controllable crystal content and biodegradability; while noncrystallizable PDLLA provides hydrophobicity and thermal stability in the system. Differential scanning calorimetry (DSC) combined with scanning electron microscope (SEM) showed that the morphology of the blend films was uniform on a macroscopic scale, yet with tunable micro-phase patterns at different mixing ratios. Fourier transform infrared analysis (FTIR) revealed that structures of the blend system, such as beta-sheet crystal content, gradually changed with the mixing ratios. All blended samples have better stability than pure SF and PLA samples as evidenced by thermogravimetric analysis. Protease XIV enzymatic study showed that the biodegradability of the blend samples varied with their blending ratios and microscale morphologies. Significantly, the topology of the micro-phase patterns on the blends can promote cell attachment and manipulate the cell growth and proliferation. This study provided a useful platform for understanding the fabrication strategies of protein-synthetic polymer composites that have direct biomedical and green chemistry applications.

A Biomimetic Hierarchical Nanointerface Orchestrates Macrophage Polarization and Mesenchymal Stem Cell Recruitment To Promote Endogenous Bone Regeneration.

The host immune response to bone biomaterials is vital in determining scaffold fates and bone regeneration outcomes. The nanometer-scale interface of biomaterials, which independently controls physical inputs to cells, regulates osteogenic differentiation of stem cells and local immune response. Herein, we fabricated biomimetic hierarchical intrafibrillarly mineralized collagen (HIMC) with a bone-like staggered nanointerface and investigated its immunomodulatory properties and mesenchymal stem cell (MSC) recruitment during endogenous bone regeneration. The acquired HIMC potently induced neo-bone formation by promoting CD68+CD163+ M2 macrophage polarization and CD146+STRO-1+ host MSC recruitment in critical-sized bone defects. Mechanistically, HIMC facilitated M2 macrophage polarization and interleukin (IL)-4 secretion to promote MSC osteogenic differentiation. An anti-IL4 neutralizing antibody significantly reduced M2 macrophage-mediated osteogenic differentiation of MSCs. Moreover, HIMC-loaded-IL-4 implantation into critical-sized mandible defects dramatically enhanced bone regeneration and CD68+CD163+ M2 macrophage polarization. The depletion of monocyte/macrophages by clodronate liposomes significantly impaired bone regeneration by HIMC, but did not affect MSC recruitment. Thus, in emulating natural design, the hierarchical nanointerface possesses the capacity to recruit host MSCs and promote endogenous bone regeneration by immunomodulation of macrophage polarization through IL-4.

Biomaterial Surface and Interface Analysis by Means of Time-of-Flight Secondary Ion Mass Spectrometry

Biomaterial Surface and Interface Analysis by Means of Time-of-Flight Secondary Ion Mass Spectrometry

Artificial shear stress effects on leukocytes at a biomaterial interface.

Medical devices, such as ventricular assist devices (VADs), introduce both foreign materials and artificial shear stress to the circulatory system. The effects these have on leukocytes and the immune response are not well understood. Understanding how these two elements combine to affect leukocytes may reveal why some patients are susceptible to recurrent device-related infections and provide insight into the development of pump thrombosis. Biomaterials-DLC: diamond-like carbon-coated stainless steel; Sap: single-crystal sapphire; and Ti: titanium alloy (Ti6 Al4 V) were attached to the parallel plates of a rheometer. Whole human blood was left between the two discs for 5minutes at +37°C with or without the application of shear stress (0s-1 or 1000s-1 ). Blood was removed and used for complete blood cell counts, flow cytometry (leukocyte activation, cell death, microparticle generation, phagocytic ability, and reactive oxygen species [ROS] production), and the production of pro-inflammatory cytokines. L-selectin expression on monocytes was decreased when blood was exposed to the biomaterials both with and without shear. Applying shear stress to blood on a Sap and Ti surface led to activation of neutrophils shown as decreased L-selectin expression. Sap and Ti blunted the LPS-stimulated macrophage migration inhibitory factor (MIF) production, most notably when sheared on Ti. The biomaterials used here have been shown to activate leukocytes in a static environment. The introduction of shear appears to exacerbate this activation. Interestingly, a widely accepted biocompatible material (Ti) utilized in many different types of devices has the capacity for immune cell activation and inhibition of MIF secretion when combined with shear stress. These findings contribute to our understanding of the contribution of biomaterials and shear stress to recurrent infections and vulnerability to sepsis in some VAD patients as well as pump thrombosis.

Bioinspired interface design modulates pathogen and immunocyte responses in biomaterial-centered infection combination therapy

Biologically inspired biomaterial interface design can regulate the behaviors of pathogens and immunocytes for “infection combination therapy”.