Mean deformation metrics for quantifying 3D cell-matrix interactions without requiring information about matrix material properties.

Mechanobiology relates cellular processes to mechanical signals, such as determining the effect of variations in matrix stiffness with cell tractions. Cell traction recorded via traction force microscopy (TFM) commonly takes place on materials such as polyacrylamide- and polyethylene glycol-based gels. Such experiments remain limited in physiological relevance because cells natively migrate within complex tissue microenvironments that are spatially heterogeneous and hierarchical. Yet, TFM requires determination of the matrix constitutive law (stress-strain relationship), which is not always readily available. In addition, the currently achievable displacement resolution limits the accuracy of TFM for relatively small cells. To overcome these limitations, and increase the physiological relevance of in vitro experimental design, we present a new approach and a set of associated biomechanical signatures that are based purely on measurements of the matrix's displacements without requiring any knowledge of its constitutive laws. We show that our mean deformation metrics (MDM) approach can provide significant biophysical information without the need to explicitly determine cell tractions. In the process of demonstrating the use of our MDM approach, we succeeded in expanding the capability of our displacement measurement technique such that it can now measure the 3D deformations around relatively small cells (∼10 micrometers), such as neutrophils. Furthermore, we also report previously unseen deformation patterns generated by motile neutrophils in 3D collagen gels.

Nanotechnology Treatment Options for Osteoporosis and Its Corresponding Consequences.

Unfortunately, osteoporosis, as a worldwide disease, is challenging human health with treatment only available for the symptoms of osteoporosis without managing the disease itself. Osteoporosis can be linked as the common cause of fractures and increased mortality among post-menopausal women, men, and the elderly. Regrettably, due to osteoporosis, incidents of fractures are more frequent among the presented populations and can be afflictive for carrying out everyday life activities. Current treatments of osteoporosis encompass changing lifestyles, taking orthopedic drugs, and invasive surgeries. However, these treatment options are not long lasting and can lead to complications after post-surgical life. Therefore, to solve this impairment, researchers have turned to nanotechnologies and nanomaterials to create innovative and alternative treatments associated with the consequences of osteoporosis. This review article provides an introduction to osteoporotic compression vertebral fractures (OVCFs) and current clinical treatments, along with the rationale and efficacy of utilizing nanomaterials to modify and improve biomaterials or instruments. The methods of applying bioactive agents (bone morphogenetic protein-2 (BMP-2), parathyroid hormone 1-34 (PTH 1-34)), as well as 3D printing will be presented from an osteoporosis treatment perspective. Additionally, the application of nanoparticles and nanotube arrays onto the current surgical treatments and orthopedic drug administration methods addressed will show that these systems reinforce a better mechanical performance and provide precise and slow-releasing drug delivery for better osseointegration, bone regeneration, and bone strength. In summary, nanomaterials can be seen as an alternative and more effective treatment for individuals with osteoporosis.

The nano-effect: improving the long-term prognosis for musculoskeletal implants.

Due to their superior cytocompatible, mechanical, electrical, optical, catalytic, and magnetic properties, nanomaterials (materials with one dimension ≤100 nm) have been investigated intensely for numerous medical applications including, most notably, as improved tissue engineering materials and in situ sensors. In particular, compared to conventional materials (materials without one dimension ≤100 nm) used for orthopedic applications, nanomaterials have demonstrated an enhanced capability to restore, maintain, and improve bone tissue formation while inhibiting inflammation and infection. This review article elucidates several promising examples of nanomaterials (including polymers, metals, and ceramics) to improve musculoskeletal implant performance in terms of enhanced bone cell functions, reduced inflammation, and inhibiting infection. With respect to the emergence of tissue engineering in orthopedic applications, this review summarizes recent efforts to develop nanostructured polymers and self-assembled nano-materials, which have improved bone growing properties than traditional permanent orthopedic medical devices.

A versatile three-dimensional foam fabrication strategy for soft and hard tissue engineering.

The fabrication strategies of three-dimensional porous biomaterials have been extensively studied and well established in the past few decades, yet the biocompatibility and versatility of porous architecture preparation is still lacking. Herewith, we present a novel and green 3D porous foam fabrication technique for both soft and hard engineering. By utilizing the gelatinization and retrogradation properties of starches, stabilized porous constructs made of various building blocks, from living cells to ceramic particles, were created for the first time. In soft tissue engineering applications, 3D cultured tissue foam (CTF) with controlled cell release properties was developed, and foams constituting osteoblasts, fibroblasts and vascular endothelial cells all exhibited high mechanical stability and preservation of cell viability or functions. More importantly, the CTF achieved sustained self-release of cells controlled by serum concentration (containing amylase) and the released cells also maintained high viability and functions. In the context of hard tissue engineering applications, ceramic/bioglass (BG) foam scaffolds were developed by a similar starch-assisted foaming strategy where the resultant bone scaffolds of hydroxyapatite (HA)/BG and Si3N4/BG possessed >70% porosity with interconnected macropores (sizes 200 âˆ¼ 400 µm), fine pores (sizes 1 âˆ¼ 10 µm) and superior mechanical properties despite the high porosity. Additionally, in vitro and in vivo evaluations of the biological properties revealed that porous HA/BG foam exhibits the desired biocompatibility and osteogenesis. The in vivo study indicated new bone ingrowth after 1 week and significant increases in new bone volume after 2 weeks. In conclusion, the presented foaming strategy provides opportunities for biofabricating CTF with different cells for different target soft tissues and preparing porous ceramic/BG foams with different material components and high strengths, showing great versatility in soft and hard tissue engineering.

Antibacterial properties and toxicity from metallic nanomaterials.

The era of antibiotic resistance is a cause of increasing concern as bacteria continue to develop adaptive countermeasures against current antibiotics at an alarming rate. In recent years, studies have reported nanoparticles as a promising alternative to antibacterial reagents because of their exhibited antibacterial activity in several biomedical applications, including drug and gene delivery, tissue engineering, and imaging. Moreover, nanomaterial research has led to reports of a possible relationship between the morphological characteristics of a nanomaterial and the magnitude of its delivered toxicity. However, conventional synthesis of nanoparticles requires harsh chemicals and costly energy consumption. Additionally, the exact relationship between toxicity and morphology of nanomaterials has not been well established. Here, we review the recent advancements in synthesis techniques for silver, gold, copper, titanium, zinc oxide, and magnesium oxide nanomaterials and composites, with a focus on the toxicity exhibited by nanomaterials of multidimensions. This article highlights the benefits of selecting each material or metal-based composite for certain applications while also addressing possible setbacks and the toxic effects of the nanomaterials on the environment.

Nanomaterials for Cardiac Myocyte Tissue Engineering.

Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials.

Three-Dimensional Stem Cell Bioprinting.

Stem cells have become a revived biotechnology that is beginning to expand the field of regenerative medicine. Although stem cells are capable of regenerating tissues, current research trends tend to side on developing fully functional organs and other clinical uses including in situ stem cell repair through three-dimensional printing methods. Through several tests and techniques, it can be shown that most stem cell printing methods are possible and that most tests come out with high cell viability. Furthermore, the importance of bioprinting is to benefit the field of regenerative medicine, which looks into artificial organ transplants for the thousands of patients without donors. Although the field is not brand new, understanding the integration and use of additive manufacturing with biomaterials is essential in developing fully functional organs. There is a heavy emphasis on the biomaterials themselves since they have a crucial role in creating an organ that is mechanically robust and adaptable in vivo. Covered in this review article are many featured tests, which also touch on the importance of including a biomaterial that is capable of maintaining a viable microenvironment. These include biomaterials such as hydrogels, biopolymers, and synthetic extra cellular matrices (ECM) built for stem cells to proliferate, differentiate, and give freedom to cell communication after printing.

Recent advancements in carbon nanofiber and carbon nanotube applications in drug delivery and tissue engineering.

Since the discovery and synthesis of carbon nanotubes (CNTs) and carbon nanofibers (CNFs) over a decade ago, researchers have envisioned and discovered new potential applications for these materials. CNTs and CNFs have rapidly become a platform technology for a variety of uses, including biomedical applications due to their mechanical, electrical, thermal, optical and structural properties. CNTs and CNFs are also advantageous due to their ability to be produced in many different shapes and sizes. Since their discovery, of the many imaginable applications, CNTs and CNFs have gained a significant amount of attention and therapeutic potential in tissue engineering and drug delivery applications. In recent years, CNTs and CNFs have made significant contributions in designing new strategies for, delivery of pharmaceuticals, genes and molecular probes into cells, stem cell therapies and assisting in tissue regeneration. Furthermore, it is widely expressed that these materials will significantly contribute to the next generation of health care technologies in treating diseases and contributing to tissue growth. Hence, this review seeks to explore the recent advancements, current status and limitations of CNTs and CNFs for drug delivery and tissue engineering applications.

Planar Gradient Diffusion System to Investigate Chemotaxis in a 3D Collagen Matrix.

The importance of cell migration can be seen through the development of human life. When cells migrate, they generate forces and transfer these forces to their surrounding area, leading to cell movement and migration. In order to understand the mechanisms that can alter and/or affect cell migration, one can study these forces. In theory, understanding the fundamental mechanisms and forces underlying cell migration holds the promise of effective approaches for treating diseases and promoting cellular transplantation. Unfortunately, modern chemotaxis chambers that have been developed are usually restricted to two dimensions (2D) and have complex diffusion gradients that make the experiment difficult to interpret. To this end, we have developed, and describe in this paper, a direct-viewing chamber for chemotaxis studies, which allows one to overcome modern chemotaxis chamber obstacles able to measure cell forces and specific concentration within the chamber in a 3D environment to study cell 3D migration. More compelling, this approach allows one to successfully model diffusion through 3D collagen matrices and calculate the coefficient of diffusion of a chemoattractant through multiple different concentrations of collagen, while keeping the system simple and user friendly for traction force microscopy (TFM) and digital volume correlation (DVC) analysis.

Growth characteristics of different heart cells on novel nanopatch substrate during electrical stimulation.

During a heart attack, the heart's oxygen supply is cut off, and cardiomyocytes perish. Unfortunately, once these tissues are lost, they cannot be replaced and results in cardiovascular disease-the leading cause of deaths worldwide. Advancements in medical research have been targeted to understand and combat the death of these cardiomyocytes. For example, new research (in vitro) has demonstrated that one can expand cardiomyocyte adhesion and proliferation using polylactic-co-glycolic acid (PLGA) (50:50 (weight percent)) supplemented with carbon nanofibers (CNFs) to create a cardiovascular patch. However, the examination of other cardiovascular cell types has not been investigated. Therefore, the purpose of this present in vitro study was to determine cell growth characteristics of three different important cardiovascular cell types (aortic endothelial, fibroblast and cardiomyocyte) onto the substrate. Cells were seeded onto different PLGA:CNF ratio composites to determine if CNF density has an effect on cell growth, both in static and electrically stimulated environments. During continuous electrical stimulation (rectangle, 2 nm, 5 V/cm, 1 Hz), cardiomyocyte cell density increased in comparison to its static counterparts after 24, 72 and 120 hours. A minor rise in Troponin I excretion in electrical stimulation compared to static conditions indicated nominal cardiomyocyte cell function during cell experiments. Endothelial and fibroblast cell growth experiments indicated the material hindered or stalled proliferation during both static and electrical stimulation experiments, thus supporting the growth of cardiomyocytes onto the dead tissue zone. Furthermore, the results specified that CNF density did have an effect on PLGA:CNF composite cytocompatibility properties with the best results coming from the 50:50 [PLGA:CNF (weight percent:weight percent)] composite. Therefore, this study provides further evidence that a conductive scaffold using nanotechnology should be further research for various cardiovascular applications.

Novel injectable biomimetic hydrogels with carbon nanofibers and self assembled rosette nanotubes for myocardial applications.

The objective of the present in vitro study was to investigate cardiomyocyte functions, specifically their adhesion and proliferation, on injectable scaffolds containing RNT (rosette nanotubes) and CNF (carbon nanofibers) in a pHEMA (poly(2-hydroxyethyl methacrylate)) hydrogel to determine their potential for myocardial tissue engineering applications. RNTs are novel biocompatible nanomaterials assembled from synthetic analogs of DNA bases guanine and cytosine that self-assemble within minutes when placed in aqueous solutions at body temperatures. These materials could potentially improve cardiomyocyte functions and solidification time of pHEMA and CNF composites. Because heart tissue is conductive, CNFs were added to pHEMA to increase the composite's conductivity. Our results showed that cardiomyocyte density increased after 4 h, 1 day, and 3 days with greater amounts of CNFs and greater amounts of RNTs in pHEMA (up to 10 mg mL(-1) CNFs and 0.05 mg mL(-1) RNTs). Factors that may have increased cardiomyocyte functions include greater wettability, conductivity, and an increase in surface nanoroughness with greater amounts of CNFs and RNTs. In effect, contact angles measured on the surface of the composites decreased while the conductivity and surface roughness increased as CNFs and RNTs content increased. Lastly, the ultimate tensile modulus decreased for composites with greater amounts of CNFs. In summary, the properties of these injectable composites make them promising candidates for myocardial tissue engineering applications and should be further studied.

Mechanisms of greater cardiomyocyte functions on conductive nanoengineered composites for cardiovascular application.

BACKGROUND: Recent advances in nanotechnology (materials with at least one dimension between 1 nm and 100 nm) have led to the use of nanomaterials in numerous medical device applications. Recently, nanomaterials have been used to create innovative biomaterials for cardiovascular applications. Specifically, carbon nanofibers (CNF) embedded in poly(lactic-co-glycolic-acid) (PLGA) have been shown to promote cardiomyocyte growth compared with conventional polymer substrates, but the mechanisms involved in such events remain unknown. The aim of this study was to determine the basic mechanism of cell growth on these novel nanocomposites. METHODS: CNF were added to biodegradable PLGA (50:50 PGA:PLA weight ratio) to increase the conductivity, mechanical and cytocompatibility properties of pure PLGA. For this reason, different PLGA to CNF ratios (100:0, 75:25, 50:50, 25:75, and 0:100 wt%) with different PLGA densities (0.1, 0.05, 0.025, and 0.0125 g/mL) were used, and their compatibility with cardiomyocytes was assessed. RESULTS: Throughout all the cytocompatibility experiments, cardiomyocytes were viable and expressed important biomarkers, including cardiac troponin T, connexin-43, and alpha-sarcomeric actin (α-SCA). Adhesion and proliferation experiments indicated that a PLGA density of 0.025 g/mL with a PLGA to CNF ratio of 75:25 and 50:50 (wt%) promoted the best overall cell growth, ie, a 55% increase in cardiomyocyte density after 120 hours compared with pure PLGA and a 75% increase compared with the control at the same time point for 50:50 (wt%). The PLGA:CNF materials were conductive, and their conductivity increased as greater amounts of CNF were added to pure PLGA, from 0 S · m(-1) for pure PLGA (100:0 wt%) to 5.5 × 10(-3) S · m(-1) for pure CNF (0:100 wt%), as compared with natural heart tissue (ranging from 0.16 S · m(-1) longitudinally to 0.005 S · m(-1) transversely). Tensile tests showed that the addition of CNF increased the tensile strength to mimic that of natural heart tissue, ie, 0.15 MPa for 100% PLGA to 5.41 MPa for the 50:50 (PLGA to CNF [wt%:wt%]) ratio at 0.025 g/mL. Atomic force microscopy indicated that the addition of CNF to PLGA increased the material surface area from 10% (100:0 [PLGA to carbon nanofiber (wt%:wt%)]) to over 60% (50:50 [PLGA to carbon nanofibers (wt%:wt%)]). Lastly, the adsorption of specific proteins (fibronectin and vitronectin) showed significantly more adsorption for the 50:50 PLGA to CNF (wt%:wt%) ratio at 0.025 g/mL PLGA compared with pure PLGA, which may be why cardiomyocyte function increased on CNF-enriched composites. CONCLUSION: This study demonstrates that cardiomyocyte function was enhanced on 50:50 PLGA to CNF (wt%:wt%) composite ratios at 0.025 g/mL PLGA densities because they mimicked native heart tissue tensile strength/conductivity and increased the adsorption of proteins known to promote cardiomyocyte function.

Poly(lactic-co-glycolic acid): carbon nanofiber composites for myocardial tissue engineering applications.

The objective of the present in vitro research was to investigate cardiac tissue cell functions (specifically cardiomyocytes and neurons) on poly(lactic-co-glycolic acid) (PLGA) (50:50 wt.%)-carbon nanofiber (CNF) composites to ascertain their potential for myocardial tissue engineering applications. CNF were added to biodegradable PLGA to increase the conductivity and cytocompatibility of pure PLGA. For this reason, different PLGA:CNF ratios (100:0, 75:25, 50:50, 25:75, and 0:100 wt.%) were used and the conductivity as well as cytocompatibility of cardiomyocytes and neurons were assessed. Scanning electron microscopy, X-ray diffraction and Raman spectroscopy analysis characterized the microstructure, chemistry, and crystallinity of the materials of interest to this study. The results show that PLGA:CNF materials are conductive and that the conductivity increases as greater amounts of CNF are added to PLGA, from 0 S m(-1) for pure PLGA (100:0 wt.%) to 5.5×10(-3) S m(-1) for pure CNF (0:100 wt.%). The results also indicate that cardiomyocyte density increases with greater amounts of CNF in PLGA (up to 25:75 wt.% PLGA:CNF) for up to 5 days. For neurons a similar trend to cardiomyocytes was observed, indicating that these conductive materials promoted the adhesion and proliferation of two cell types important for myocardial tissue engineering applications. This study thus provides, for the first time, an alternative conductive scaffold using nanotechnology which should be further explored for cardiovascular applications.