In this article, site-specific functionalized keratoprosthesis (KPro) was accomplished to meet epithelial on-growth on the anterior optical surface, inhibit cell adhesion on the posterior optic surface, and promote cell ingrowth at the peripheral tissue-haptic-flange interface toward tissue integration. Gelatin immobilization on PC4 hydrogel surfaces was achieved through acid hydrolysis followed by EDC/NHS chemistry, and polyethylene glycol-diacrylate (PEGDA)-modified inter-penetrating network (IPN) surfaces were prepared using photo-polymerization of ethylene glycol-diacrylate (EGDA) for enhancing and inhibiting cellular growth, respectively. The surface chemical structures of modified hydrogels were characterized using attenuated total reflectance-infrared (ATR-IR) spectroscopy and a bicinchoninic acid (BCA) protein adsorption assay. Further, suitable differentially functionalized surfaces were prepared and characterized using the universal testing machine (UTM), refractometer, atomic force microscopy (AFM), and contact angle measurements to understand mechanical, optical, surface morphological, and wettability properties, respectively. Finally, in vitro site-specific cell adhesion, cell inhibition, and cell ingrowth functionalities were tested using isolated goat corneal limbal epithelial stem cells and corneal stromal fibroblast cells, respectively. Overall, the two connective articles represent a successful endeavor to develop a more esthetically pleasing, mechanically stable, tissue-free hydrogel KPro with site-specific surface functionality nearly mimicking the cornea's functionality. A further pre-clinical investigation is necessary to advance this functional novel KPro to reality, especially the tissue integration aspect. Differentially surface functionalized semi-bioresorbable keratoprosthesis. image

In the field of bone tissue engineering, recently developed Zn alloy scaffolds are considered potential candidates for biodegradable implants for bone regeneration and defect reconstruction. However, the clinical success of these alloys is limited due to their insufficient surface bioactivities. Further, the higher concentration of Zn2+ produced during degradation promotes antibacterial activity, but deteriorates osteogenic properties. This study fabricated an Azadirachta indica (neem)-assisted brushite-hydroxyapatite (HAp) coating on the recently developed Zn-2Cu-0.5Mg alloy to tackle the above dilemma. The microstructure, degradation behavior, antibacterial activity, and hemocompatibility, along with in vitro and in vivo cytocompatibility of the coated alloys, are systematically investigated. Microstructural analysis reveals flower-like morphology with uniformly grown flakes for neem-assisted deposition. The neem-assisted deposition significantly improves the adhesion strength from 12.7 to 18.8 MPa, enhancing the mechanical integrity. The potentiodynamic polarization study shows that the neem-assisted deposition decreases the degradation rate, with the lowest degradation rate of 0.027 mm/yr for the ZHN2 sample. In addition, the biomineralization process shows the apatite formation on the deposited coating after 21 days of immersion. In vitro cytotoxicity assay exhibits the maximum cell viability of 117% for neem-assisted coated alloy in 30% extract after 5d and the improved cytocompatibility which is due to the controlled release of Zn2+ ions. Meanwhile, neem-assisted coated alloy increases the ZOI by 32 and 24% for Gram-positive and Gram-negative bacteria, respectively. Acceptable hemolysis (<5%) and anticoagulation parameters demonstrate a promising hemocompatibility of the coated alloy. In vivo implantation illustrates a slight inflammatory response and vascularization after 2 weeks of subcutaneous implantation, and neo-bone formation in the defect areas of the rat femur. Micro-CT and histology studies demonstrate better osseointegration with satisfactory biosafety response for the neem-assisted coated alloy as compared to that without neem-assisted deposition. Hence, this neem-assisted brushite-Hap coating strategy elucidates a new perspective on the surface modification of biodegradable implants for the treatment of bone defects.

Scaffolds play a crucial role in bone tissue engineering to support the defect area through bone regeneration and defect reconstruction. Promising tissue regeneration without negative repercussions and avoidance of the lifelong presence inside the body make bioresorbable metals prosper in the field of regenerative medicine. Recently, Zn and its alloys have emerged as promising biodegradable materials for their moderate degradation rate and satisfactory biocompatibility. Nevertheless, it is very challenging for cells to adhere and grow over the Zn surface alone, which influences the tissue-implant integration. In this study, an attempt has been made to systematically investigate the bioactivity responses in terms of in vitro hemocompatibility, cytotoxicity, antibacterial activity, and in vivo biocompatibility of newly developed Zn-2Cu-0.5Mn/Mg alloy scaffolds with different surface roughness. The rough surface of Zn-2Cu-0.5Mg shows the highest degradation rate of 0.16 mm/yr. The rough surface exhibits a prominent role in the adsorption of protein, further enhancing cell adhesion. Concentration-dependent alloy extract shows the highest cell proliferation for 12.5% of the extract with a maximum cell viability of 101% in Zn-2Cu-0.5Mn and 108% in Zn-2Cu-0.5Mg after 3 d. Acceptable hemolysis percentages (less than 5%) with promising anticoagulation properties are observed for all of the conditions. Enhanced antibacterial (Staphylococcus aureus and Escherichia coli) activity due to a significant effect of ions illustrates the maximum killing effect on the bacterial colony for the rough Zn-2Cu-0.5Mg alloy. In addition, it is observed that for rough Zn-2Cu-0.5Mn/Mg alloys, the inflammatory response is minimal after subcutaneous implantation, and neo-bone tissue forms in the defect areas of the rat femur with satisfactory biosafety response. The osseointegration property of the Zn-2Cu-0.5Mg alloy is comparable to that of the Zn-2Cu-0.5Mn alloy. Therefore, the rough surface of the Zn-2Cu-0.5Mg alloy has the potential to enhance biocompatibility and promote better osseointegration activity with host tissues for various biomedical applications.

Complete natural healing of skeletal tissues may take several months or even years, depending on the type and size of defects owing to slow auto-osteogenesis. Numerous techniques have been explored to gear-up the bonehealing process, as bone tissue has complex nanohybrid hierarchical meshwork containing nano apatite layers. Healing of such tissues associates with risks of pathogenic infection and ectopic bone formation. Therefore, most of the approaches fail to meet the requisite criteria to adopt in clinical practice. Carbonaceous bone substitutes may trigger healing, but an excess of it may render many adverse effects. In the current study, nanohydroxyapatite (nHA) was prepared, doped with a minute amount (0.15%) of carboxyl functionalized multiwall carbon nanotube (CCNT). The hybrid nanomaterial (CCNTH) was introduced within the synthesized biomolecule tethered segmented polyurethane-urea (SP) through in-situ technique and scaffolds were fabricated by electrospinning technique. CCNT doping improves the tensile strength and the hardness of the nano-scaffold by 94.5% and 173.6%, respectively. In vitro MTT assay, FESEM and protein adsorption study indicated the excellent cytocompatibility of the nanohybrid scaffolds. The qRT-PCR study indicates the significant expression of the osteogenic bone marker, osteocalcin (OCN) and the alkaline phosphatase (ALP) of the CCNTH incorporated nanohybrid scaffolds compared to the SP scaffold. Furthermore, the in vivo rat tibia and skull model exhibit excellent bone regeneration efficacy compared to the control without showing any sign of organ toxicity. Thus, a minute amount of CCNT doped nHA incorporated SP based micro-porous nanohybrid scaffold can be used as an alternate suitable biomaterial for osteoinduction application.

Three Zn-based alloys (Zn1Cu, Zn2Cu, and Zn3Cu) were developed by the addition of Cu (1, 2, and 3 wt %) into commercially pure Zn. This report systematically investigates the potential for these newly developed Zn-based alloys as biodegradable materials. Microstructural studies reveal the presence of spherical-shaped nanosized precipitates of ε-CuZn4 in the Zn1Cu alloy, whereas Zn2Cu and Zn3Cu alloys exhibit the presence of both micron- and nanosized precipitates of ε-CuZn4. The mechanical properties such as hardness, tensile and compressive strengths improve significantly with an increase in the amount of Cu in the alloy. The Zn3Cu alloy exhibits the highest yield strength (225 ± 9 MPa) and ultimate tensile strength (330 ± 12 MPa) among all of the alloys, which are ∼2.7 and 2 times higher than those of pure Zn. In vitro degradation behavior is evaluated by the potentiodynamic polarization study and immersion testing in Hank's solution for 20 and 75 days. The corrosion rate after both polarization and immersion testing follows the order of pure Zn < Zn1Cu < Zn3Cu < Zn2Cu. An electrochemical impedance spectroscopy (EIS) study also concludes that Zn2Cu shows the lowest corrosion resistance. The % cell viability values of 3T3 fibroblasts cells after 5 days of culture in a 50% diluted extract of pure Zn, Zn2Cu, and Zn3Cu alloys are 76 ± 0.024, 86.18 ± 0.033, and 92.9 ± 0.026%, respectively, establishing the improved cytocompatibility of the alloys as compared to pure Zn. Furthermore, an antibacterial study also reveals that the Zn3Cu alloy exhibits 80, 67, and 100% increases in the zone of inhibition (ZOI) for Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa bacteria, respectively, as compared to that of pure Zn.

Critical bone defects with a sluggish rate of auto-osteoconduction and imperfect reconstruction are motivators for the development of an alternate innovative approach for the regeneration of bone. Tissue engineering for bone regeneration signifies an advanced way to overcome this problem by creating an additional bone tissue substitute. Among different fabrication techniques, the 3D printing technique is obviously the most efficient and advanced way to fabricate an osteoconductive scaffold with a controlled porous structure. In the current article, the polycarbonate and polyester diol based polyurethane-urea (P12) was synthesized and 3D porous nanohybrid scaffolds (P12/TP-nHA) were fabricated using the 3D printing technique by incorporating the osteoconductive nanomaterial titanium phosphate adorned nanohydroxyapatite (TP-nHA). To improve the bioactivity, the surface of the fabricated scaffolds was modified with the immobilized biomolecule polydopamine (PDA) at room temperature. XPS study as well as the measurement of surface wettability confirmed the higher amount of PDA immobilization on TP-nHA incorporated nanohybrid scaffolds through the dative bone formation between the vacant d orbital of the incorporated titanium ion and the lone pair electron of the catechol group of dopamine. The incorporated titanium phosphate (TP) increased the tensile strength (53.1%) and elongation at break (96.8%) of the nanohybrid composite as compared to pristine P12. Moreover, the TP incorporated nanohybrid scaffold with calcium and phosphate moieties and a higher amount of immobilized active biomolecule improved the in vitro bioactivity, including the cell viability, cell proliferation, and osteogenic gene expression using hMSCs, of the fabricated nanohybrid scaffolds. A rat tibia defect model depicted that the TP incorporated nanohybrid scaffold with immobilized PDA enhanced the in vivo bone regeneration ability compared to the control sample without revealing any organ toxicity signifying the superior osteogenic bioactivity. Thus, a TP augmented polydopamine immobilized polyurethane-urea based nanohybrid 3D printed scaffold with improved physicochemical properties and osteogenic bioactivity could be utilized as an excellent advanced material for bone regeneration substitute.

Diagnosing heavy metals poisoning in human beings is of paramount importance. In this work, we present the design of a biocompatible FexNi(1-x)O hierarchical nanostructure-based sensor for ultraselective detection of arsenate (As(V)) ions in biological environments (e.g., body fluids, blood plasma, etc.). A novel iron doping technique was employed to fabricate the nanostructures rich with Fe cores to induce ultraselectivity toward arsenates. These nanostructures were used as dispersed markers and thin films deposited on Si/SiO2 substrates to support in vivo and in vitro detection of As(V) ions. The device demonstrated excellent sensitivity with a maximum response of 64.7% (for 1000 ppm As(V) ions) with a limit of detection of 1 ppb in blood plasma. The sensor's response time (tau(r)) was 5 s with 95.48% recovery with a maximum error of +/- 0.549% after three washes. The device showed excellent response stability for 63 days with a maximum error of +/- 1.27%. The sensor devices were highly reproducible, with a maximum variation of +/- 0.6% in response for a batch of four devices. Due to Fe doping, the nanostructures in suspension demonstrated as arsenate markers with excellent cytocompatibility (with dosage up to 1 mg/mL) for human umbilical vein endothelial cells and 3T3 fibroblasts (LDH < 120 and cell viability similar to 80%) till 48 h of incubation. The sensing mechanism suggested that the nanostructures not only detect arsenates but also prevent their substantial reduction to arsenites under anoxic environments. Thus, the sensors may show considerable progress toward early arsenate detection in living systems.

Several disease conditions, such as cancer metastasis and atherosclerosis, are deeply connected with the complex biophysical phenomena taking place in the complicated architecture of the tiny blood vessels in human circulatory systems. Traditionally, these diseases have been probed by devising various animal models, which are otherwise constrained by ethical considerations as well as limited predictive capabilities. Development of an engineered network-on-a-chip, which replicates not only the functional aspects of the blood-carrying microvessels of human bodies, but also its geometrical complexity and hierarchical microstructure, is therefore central to the evaluation of organ-assist devices and disease models for therapeutic assessment. Overcoming the constraints of reported resource-intensive fabrication techniques, here, we report a facile, simple yet niche combination of surface engineering and microfabrication strategy to devise a highly ordered hierarchical microtubular network embedded within a polydimethylsiloxane (PDMS) slab for dynamic cell culture on a chip, with a vision of addressing the exclusive aspects of the vascular transport processes under medically relevant paradigms. The design consists of hierarchical complexity ranging from capillaries (∼80 μm) to large arteries (∼390 μm) and a simultaneous tuning of the interfacial material chemistry. The fluid flow behavior is characterized numerically within the hierarchical network, and a confluent endothelial layer is realized on the inner wall of microfluidic device. We further explore the efficacy of the device as a vascular deposition assay of circulatory tumor cells (MG-63 osteosarcoma cells) present in whole blood. The proposed paradigm of mimicking an in vitro vascular network in a low-cost paradigm holds further potential for probing cellular dynamics as well as offering critical insights into various vascular transport processes.

Bone is the major connective tissue maintaining the structural integrity of the human body. However, fracture and many skeletal degenerative diseases can compromise this function. Thus, therapeutics related to bone degeneration are of significant research interest and require good in vitro models for such therapeutic evaluation. Bone is a highly vascularized tissue and incorporation of this feature is significantly important for mimicking the osteogenic microenvironment. In the current study, we developed a vascularized flat bone model via simultaneous mechanical actuation of mechanical strain and fluid shear. The mechanical strain was achieved by static magnetic field actuation of a magnetic nanocomposite scaffold. The fluid shear was generated by developing a micropattern on the magnetic nanocomposite via replica molding and laser-based microfabrication. From the live cell imaging window of the microdevice, both bone and vasculature like cellular morphology was observed. The SEM study showed thick ECM deposition in the dynamic culture. In the PCR study, both osteogenic (Col-1, osteocalcin) and angiogenic phenotypes (PECAM) were observed in the dynamic culture scaffolds while chondrogenic marker (Col-2) was downregulated.

In the realm of diagnostics and emerging therapeutics, healthcare sectors like therapeutics, point-of-care diagnostics (POCT) and theranostics have been witnessing a paradigm shift. The complexity of life-style in present scenario demands sophisticated and dedicated medical devices that can be deployed for obtaining desired outcomes both in quick succession and also impart long-term benefits. The advent of such emerging healthcare devices will immensely impact patient health especially when the turn-around time is critical, chronic injuries, burn patients, cardiac arrest or brain injury being some of the examples for such conditions. It is of paramount importance to highlight that a well-engineered platform is the core component of any therapeutic system. Designing platforms with multidimensional functionality provides a stable microenvironment, capable of mimicking the dynamic in vivo conditions thus securing the success aspect of any medical device. The interaction of cells, tissues and biomolecules with its microenvironment involve sequential coherence of complex biochemical events leading to occurrence of desired bio-affinitive reactions. For a heterogeneous system, bio-affinitive reactions demands precise control over the microenvironment for specific therapeutic applications as fate of biomolecules depends on their surroundings and may face steric hindrance and easily lose their activity when brought in close proximity to such platforms.

Additive manufacturing in the healthcare sector has promisingly paved its way since the failure of implants, and tissue analogs resulted from the improper fabrication strategies of conventional manufacturing procedures. High energy source additive manufacturing strategies are optimum in regard to the appropriate mimicking of the shape of the host tissue or organ. However, there are subtle issues which critically impact the final outcome of the whole process, i.e., imaging of the patients’ tissue, reconstruction of the model, fabrication, and surgery. In many of the high-energy laser sintering facilities, the choice of the materials is very shallow. Moreover, cell-laden constructs are highly questionable to be used within these processes as it requires very low temperature (~37 °C) and low stress in the environment for the cells to be functional. Due to these drawbacks of other procedures, extrusion-based procedures have become popularly explored and utilized, leading the current additive manufacturing front in healthcare. Further advancement in 3D printing was also discussed which were able to print structures in the submicron range. A newly introduced technique, two-photon-based polymerization—direct laser writing-based printing of microstructures is gaining much attention. Owing to its capability to print three-dimensional architectures, which can exactly mimic the in vivo microenvironment, the structures can be easily deployed to study cell–cell or cell–matrix interaction. Moreover, resolution and complexity of the microstructures printed using the above technique can be used as an in vivo equivalent model for studying cell–drug interactions. The utility of 3D printing for fabrication of microfluidic devices was also discussed as such devices can be further adopted for microbioreactor applications. The fabrication of such microfluidic bioreactor-based system helps to exactly mimic the biochemical or biophysical parameters like temperature, pH, or concentration of nutrients. The study concludes that 3D printing technique can be adopted not only for creating excellent microstructures or systems for futuristic tissue engineering application.

The extensive and diversified applications of the well-known plasmonic nanoparticle systems along with their easy and environment-friendly synthesis strategies drive us to investigate in-depth this important research field. In the current scenario, our present study deals with an important plasmonic nanomaterial, i.e., globular protein, and human serum albumin (HSA)-conjugated gold nanoparticle (HSA-Au NP) system. The well-known chemical denaturants, urea and guanidine hydrochloride (GdnHCl or GnHCl), are investigated to show detrimental effects toward the formation of gold nanoparticles; however, the effect of GdnHCl is observed to be much prominent compared to that of urea. The synthesized nanoparticle system is found to be highly biocompatible from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based cytotoxicity assay, and therefore, the applications of encapsulation of the well-known anticancer drug molecule, doxorubicin hydrochloride (Dox), in the nanoparticle system are further studied. In this drug encapsulation study, drug-metal complexation between Dox and HAuCl4 center dot 3H(2)O has been discussed elaborately. Similar to the nanoparticle formation, the effects of denaturants on drug encapsulation have also been discovered, and interestingly, it has been observed that urea plays a positive role, whereas GdnHCl plays a negative or detrimental role toward drug encapsulation in the synthesized gold nanoparticle system. The detailed photophysical mechanisms behind the drug encapsulation in the synthesized plasmonic nanosystem at every stage have also been explored. Overall, this study will conclusively explain the influences of the extensively used chemical denaturants on the synthesis and drug encapsulation behaviors of a well-known protein-conjugated gold nanoparticle, and as a consequence, it can be highly useful and acceptable to the biomedical and pharmaceutical research communities.

Metal/metal oxide nanoparticles have long been used as an antibacterial substitute, but fabrication of an effective carrier or delivery matrix for achieving a sustain release profile with high bactericidal efficacy alongwith good cytocompatibility is still an unresolved challenge. Herein, the study demonstrates a facile and unique route to fabricate a hierarchical nanobiocomposite with effective loading of ZnO/silver nanoparticles (Ag-NPs) in order to attain excellent bactericidal efficacy with good and sustainable release profile. Surface functionalized eggshell membranes (ESM) were deployed as three-dimensional loading matrices for efficient loading of ZnO/Ag-NPs. A simple sonochemical guided approach was adopted to synthesize ZnO nanoflakes in situ onto the microfibrous ESM and decorate it with Ag-NPs to fabricate a nanobiocomposite. Microstructural analysis confirms successful anchorage of ZnO nanoflakes and Ag-NPs on microfibrous eggshell membrane thus reinstating hierarchical morphology of the nanobiocomposites. FT-IR spectra confirms the biochemical composition whereas XPS analysis ratifies the interaction between ZnO and Ag-NPs further substantiating metallic state of Ag. ICP-MS studies affirms excellent and sustainable release profile of nanoparticles from the nanobiocomposites. Owing to the synergistic activity of ZnO/Ag-NPs, the nanobiocomposites demonstrated exceptional bactericidal activity against Gram-negative, E. coli or P. aeruginosa, and Gram-positive, S. aureus or B. subtilis, bacterial cells. Moreover, inherent antibacterial property of microfibrous natural ESM contributes positively toward the overall bactericidal activity. Further, a direct exposure of nanobiocomposites with NIH 3T3 cells revealed the biocompatible nature of developed matrices. Prolonged exposure also indicated that the 3T3 cells tend to adhere onto the microfibrous nanobiocomposite without any observable deformation in cellular morphology. The architectural tribology and excellent bactericidal performance of the nanobiocomposites along with its cytocompatible nature manifests its application as an alternate platform for varying biomedical applications.

The vast domain of regenerative medicine comprises complex interactions between specific cells’ extracellular matrix (ECM) towards intracellular matrix formation, its secretion, and modulation of tissue as a whole. In this domain, engineering scaffold utilizing biomaterials along with cells towards formation of living tissues is of immense importance especially for bridging the existing gap of late; nanostructures are offering promising capability of mechano-biological response needed for tissue regeneration. Materials are selected for scaffold fabrication by considering both the mechanical integrity and bioactivity cues they offer. Herein, polycaprolactone (PCL) (biodegradable polyester) and ‘nature’s wonder’ biopolymer silk fibroin (SF) are explored in judicious combinations of emulsion electrospinning rather than conventional electrospinning of polymer blends. The water in oil (W/O) emulsions’ stability is found to be dependent upon the concentration of SF (aqueous phase) dispersed in the PCL solution (organic continuous phase). The spinnability of the emulsions is more dependent upon the viscosity of the solution, dominated by the molecular weight of PCL and its concentration than the conductivity. The nanofibers exhibited distinct core-shell structure with better cytocompatibility and cellular growth with the incorporation of the silk fibroin biopolymer.

Coronary artery disease (CAD), especially atherosclerosis is the major contributor of untimely and abrupt death of the maximum population of the world. Balloon angioplasty has become a popular choice of cardiac intervention owing to its minimal invasive quality for the treatment of stenosis. Of the various available commercial coronary stents in the market we have taken six commercial stents for our experimental study namely: PS stent, CYPHER stent (Cordis, J & J), S670 stent, Driver stent (Medtronic, USA), Taxus Express stent, Element stent (Boston Scientific, USA). Geometry modeling, meshing and computational simulation is done to mimic real life biological conditions (with assumptions). Of the total 192 simulation results, Element stent design has come up to be the better stent design among others and cobalt alloys specially cobalt alloy MP35N (ASTM F562) has shown the best performance by developing least von mises stress, in terms of material perspective.