Design of Novel Perovskite-Based Polymeric Poly(l-Lactide-Co-Glycolide) Nanofibers with Anti-Microbial Properties for Tissue Engineering.

: There is a growing need for anti-microbial materials in several biomedical application areas, such are hernia, skin grafts as well as gynecological products, owing to the complications caused by infection due to surgical biomaterials. The anti-microbial effects of silver in the form of nanoparticles, although effective, can be toxic to surrounding cells. In this study, we report, for the first time, a novel biomedical application of Ag0.3Na1.7La2Ti3O10-layered perovskite particles, blended with poly(L-lactide-co-glycolide) (PLGA), aimed at designing anti-microbial and tissue engineering scaffolds. The perovskite was incorporated in three concentrations of 1, 5, 10 and 15 w/w% and electrospun using dimethylformamide (DMF) and chloroform. The morphology of the resultant nanofibers revealed fiber diameters in the range of 408 to 610 nm by scanning electron microscopy. Mechanical properties of perovskite-based nanofibers also matched similar mechanical properties to human skin. We observed impressive anti-microbial activity, against Gram-negative, Gram-positive bacteria and even fungi, to Ag0.3Na1.7La2Ti3O10 in powder as well as nanofiber-incorporated forms. Furthermore, cytotoxicity assay and immunocytochemistry revealed that perovskite-based nanofibers promoted the proliferation of human dermal fibroblasts whist maintaining normal cellular protein expression. Our study shows that perovskite-nanofibers have potential as scaffolds for biomedical applications with anti-microbial needs.

Biological and mechanical interplay at the Macro- and Microscales Modulates the Cell-Niche Fate.

Tissue development, regeneration, or de-novo tissue engineering in-vitro, are based on reciprocal cell-niche interactions. Early tissue formation mechanisms, however, remain largely unknown given complex in-vivo multifactoriality, and limited tools to effectively characterize and correlate specific micro-scaled bio-mechanical interplay. We developed a unique model system, based on decellularized porcine cardiac extracellular matrices (pcECMs)-as representative natural soft-tissue biomaterial-to study a spectrum of common cell-niche interactions. Model monocultures and 1:1 co-cultures on the pcECM of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) were mechano-biologically characterized using macro- (Instron), and micro- (AFM) mechanical testing, histology, SEM and molecular biology aspects using RT-PCR arrays. The obtained data was analyzed using developed statistics, principal component and gene-set analyses tools. Our results indicated biomechanical cell-type dependency, bi-modal elasticity distributions at the micron cell-ECM interaction level, and corresponding differing gene expression profiles. We further show that hMSCs remodel the ECM, HUVECs enable ECM tissue-specific recognition, and their co-cultures synergistically contribute to tissue integration-mimicking conserved developmental pathways. We also suggest novel quantifiable measures as indicators of tissue assembly and integration. This work may benefit basic and translational research in materials science, developmental biology, tissue engineering, regenerative medicine and cancer biomechanics.

Hydroxyapatite-intertwined hybrid nanofibres for the mineralization of osteoblasts.

Advances in tissue engineering have enabled the development of bioactive composite materials to generate biomimetic nanofibrous scaffolds for bone replacement therapies. Polymeric biocomposite nanofibrous scaffolds architecturally mimic the native extracellular matrix (ECM), delivering tremendous regenerative potential for bone tissue engineering. In the present study, biocompatible poly(l-lactic acid)-co-poly(ε-caprolactone)-silk fibroin-hydroxyapatite-hyaluronic acid (PLACL-SF-HaP-HA) nanofibrous scaffolds were fabricated by electrospinning to mimic the native ECM. The developed nanofibrous scaffolds were characterized in terms of fibre morphology, functional group, hydrophilicity and mechanical strength, using SEM, FTIR, contact angle and tabletop tensile-tester, respectively. The nanofibrous scaffolds showed a higher level of pore size and increased porosity of up to 95% for the exchange of nutrients and metabolic wastes. The fibre diameters obtained were in the range of around 255 ± 13.4-789 ± 22.41 nm. Osteoblasts cultured on PLACL-SF-HaP-HA showed a significantly (p < 0.001) higher level of proliferation (53%) and increased osteogenic differentiation and mineralization (63%) for the inclusion of bioactive molecules SF-HA. Energy-dispersive X-ray analysis (EDX) data proved that the presence of calcium and phosphorous in PLACL-SF-HaP-HA nanofibrous scaffolds was greater than in the other nanofibrous scaffolds with cultured osteoblasts. The obtained results for functionalized PLACL-SF-HaP-HA nanofibrous scaffolds proved them to be a potential biocomposite for bone tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.

Tubular Tissues and Organs of Human Body--Challenges in Regenerative Medicine.

Tissue engineering of tubular organs such as the blood vessel, trachea gastrointestinal tract, urinary tract are of the great interest due to the high amount of surgeries performed annually on those organs. Development in tissue engineering in recent years and promising results, showed need to investigate more complex constructs that need to be designed in special manner. Stent technology remain the most widely used procedure to restore functions of tubular tissues after cancer treatment, or after organ removal due to traumatic accidents. Tubular structures like blood vessels, intestines, and trachea have to work in specific environment at the boundary of the liquids, solids or air and surrounding tissues and ensure suitable separation between them. This brings additional challenges in tissue engineering science in order to construct complete organs by using combinations of various cells along with the support material systems. Here we give a comprehensive review of the tubular structures of the human body, in perspective of the current methods of treatment and progress in regenerative medicine that aims to develop fully functioning organs of tubular shape. Extensive analysis of the available literature has been done focusing on materials and methods of creations of such organs. This work describes the attempts to incorporate growth factors and drugs within the scaffolds to ensure localized drug release and enhance vascularization of the organ by attracting blood vessels to the site of implantation.

Controlled release of titanocene into the hybrid nanofibrous scaffolds to prevent the proliferation of breast cancer cells.

Electrospun hybrid nanofibrous scaffolds have gained much importance in the field of tissue engineering and drug delivery applications owing to its multifaceted properties. In this study, the properties of composite polycaprolactone (PCL)/silk fibroin (SF) nanofibrous scaffolds was investigated as a potential scaffold for cell growth and also a drug eluting mat to control the proliferation of MCF-7 cells. Titanocene dichloride was chosen as the model drug to study its antitumor efficacy on MCF-7 cell lines. Fascinating properties relating to crystallization of silk fibroin and binding of drug has also been discussed for the controlled release of drugs. The presence of amino acid residues in silk fibroin plays a big role in the cell-scaffold interaction, the nature of drug binding and also its release characteristics to control the cell proliferation. Studies on material properties for the hybrid nanofibrous scaffolds showed interrelated changes in fiber diameter and mechanical behavior for the drug loaded nanofibers. Significant decrease in fiber diameters from 352±52 nm to 281±44.5 nm and sharp increase in tensile stress from 4.5 MPa to 50.3 MPa was observed for 0.03% drug loaded scaffolds with respect to PCL fibers. Cell viability and cell morphology study was performed to analyze the effect of different concentrations of titanocene dichloride loaded on PCL/silk fibroin nanofibrous scaffolds. Maximum cell viability inhibition percentage of change 26.93% was obtained for 0.03% titanocene with respect to 0.01% on day 3. The obtained results proved that the drug loaded hybrid mat to control the proliferation of MCF-7 cells at different time points and serve as a model for cancer therapy.

Multiscale ommatidial arrays with broadband and omnidirectional antireflection and antifogging properties by sacrificial layer mediated nanoimprinting.

Moth's eye inspired multiscale ommatidial arrays offer multifunctional properties of great significance in optoelectronic devices. However, a major challenge remains in fabricating these arrays on large-area substrates using a simple and scalable technique. Here we present the fabrication of these multiscale ommatidial arrays over large areas by a distinct approach called sacrificial layer mediated nanoimprinting, which involves nanoimprinting aided by a sacrificial layer. The fabricated arrays exhibited excellent pattern uniformity over the entire patterned area. Optimum dimensions of the multiscale ommatidial arrays determined by the finite-difference time domain simulations served as the design parameters for replicating the arrays on glass. A broadband suppression of reflectance to a minimum of ∼1.4% and omnidirectional antireflection for highly oblique angles of incidence up to 70° were achieved. In addition, superhydrophobicity and superior antifogging characteristics enabled the retention of optical properties even in wet and humid conditions, suggesting reliable optical performance in practical outdoor conditions. We anticipate that these properties could potentially enhance the performance of optoelectronic devices and minimize the influence of in-service conditions. Additionally, as our technique is solely nanoimprinting-based, it may enable scalable and high-throughput fabrication of multiscale ommatidial arrays.

Cross-linking of protein scaffolds for therapeutic applications: PCL nanofibers delivering riboflavin for protein cross-linking.

Nanofibers play a significant role in tissue engineering and drug delivery because of the ease with which drugs or pharmaceuticals may be incorporated into the nano-formulation. Natural protein nanofibers are cross-linked (CXLed) employing a new protocol to improve their stability for perspective usage as tissue engineering or drug delivery scaffolds. The protocol utilizes a non-toxic, natural material vitamin based CXL protocol that works well for stabilizing protein nanofibers. We have tested the generation of reactive oxygen species (ROS) from UV treated riboflavin-gelatin microfibers, film or solution that helps in gelatin (Gel) CXLing and results in improved mechanical properties. Further natural proteins Gel and fibrinogen (Fib) solutions were also CXLed using vitamin B2 (riboflavin (Rib)) released from Rib-loaded polycaprolactone (PCL) nanofibers followed by UV treatment. The sustained release of Rib from PCL nanofibers is studied with in vitro drug release experiments and in vitro hydrogel formation upon treatment with the natural protein solutions. Rib-loaded nanofibers were characterized with SEM and AFM for morphology, mechanical strength calculation and FT-IR for ensuring drug incorporation. The Rib encapsulation in the nanofiber reservoirs enables the sustained release, and the ROS generating nanofibers could find application as a patch for CXLing any protein fiber or fibrous tissue, such as ocular, skin or cardiac tissue engineering.