Tissue engineering aims at developing functional substitutes for damaged tissues and organs. Before transplantation, cells are generally seeded on biomaterial scaffolds that recapitulate the extracellular matrix and provide cells with information that is important for tissue development. Here we review the nanocomposite nature of the extracellular matrix, describe the design considerations for different tissues and discuss the impact of nanostructures on the properties of scaffolds and their uses in monitoring the behaviour of engineered tissues. We also examine the different nanodevices used to trigger certain processes for tissue development, and offer our view on the principal challenges and prospects of applying nanotechnology in tissue engineering.

/pdf/nanotechnological-strategies-for-engineering-complex-tissues-39p00hx1z2.pdf

Nanotechnological strategies for engineering complex tissues.

Nanotechnology and nanomaterials: Promises for improved tissue regeneration

The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell–microenvironment interactions continue to overturn much earl...

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

The promotion of bone regeneration by nanofibrous hydroxyapatite/chitosan scaffolds by effects on integrin-BMP/Smad signaling pathway in BMSCs

The re-exploration of the nanostructure production technique known as electrospinning was carried out in the past decade due to its simplicity and uniqueness of producing nanostructures. As nanotechnology is one of the most promising and growing technologies today, a large amount of work is being carried out in an extensive area and shows an extremely huge potential for miraculous works in the fields of medicine and biotechnology. These nanostructures were found to be of great significance because of their inherent properties such as large surface area to volume ratio and the engineered properties such as porosity, stability and permeability. The functionality and applicability of these nanostructures were further improved by incorporating secondary phases either during electrospinning or in the post-processing resulting in the composite nanostructures. These secondary phases may include metal oxides, carbon nanotubes, precious metals, gold nanoparticles and hydroxyapatite. Nanofibrous materials that mimic the native extracellular matrix (ECM) and promote the adhesion of various cells are being developed as tissue-engineered scaffolds for the skin, bone, vasculature, heart, cornea, nervous system and other tissues. The article discusses in detail the applicability of these composite fibers in energy, sensors, filters, biotechnology and details the technological issues, research challenges and future trends.

Electrospun composite nanofibers and their multifaceted applications

Today, bone diseases such as bone fractures, osteoporosis and bone cancer represent a common and significant public health problem. The design of biomimetic bone tissue engineering materials that could restore and improve damaged bone tissues provides exciting opportunities to solve the numerous problems associated with traditional orthopedic implants. Therefore, the objective of this in vitro study was to create a biomimetic orthopedic hydrogel nanocomposite based on the self-assembly properties of helical rosette nanotubes (HRNs), the osteoconductive properties of nanocrystalline hydroxyapatite (HA), and the biocompatible properties of hydrogels (specifically, poly(2-hydroxyethyl methacrylate), pHEMA). HRNs are self-assembled nanomaterials that are formed from synthetic DNA base analogs in water to mimic the helical nanostructure of collagen in bone. In this study, different geometries of nanocrystalline HA were controlled by either hydrothermal or sintering methods. 2 and 10 wt% nanocrystalline HA particles were well dispersed into HRN hydrogels using ultrasonication. The nanocrystalline HA and nanocrystalline HA/HRN hydrogels were characterized by x-ray diffraction, transmission electron microscopy, and scanning electron microscopy. Mechanical testing studies revealed that the well dispersed nanocrystalline HA in HRN hydrogels possessed improved mechanical properties compared to hydrogel controls. In addition, the results of this study provided the first evidence that the combination of either 2 or 10 wt% nanocrystalline HA and 0.01 mg ml(-1) HRNs in hydrogels greatly increased osteoblast (bone-forming cell) adhesion up to 236% compared to hydrogel controls. Moreover, this study showed that HRNs stimulated HA nucleation and mineralization along their main axis in a way that is very reminiscent of the HA/collagen assembly pattern in natural bone. In summary, the presently observed excellent properties of the biomimetic nanocrystalline HA/HRN hydrogel composites make them promising candidates for further study for bone tissue engineering applications.

http://iopscience.iop.org/article/10.1088/0957-4484/20/17/175101/pdf

Biologically inspired rosette nanotubes and nanocrystalline hydroxyapatite hydrogel nanocomposites as improved bone substitutes

Natural bone consists of hard nanostructured hydroxyapatite (HA) in a nanostructured protein-based soft hydrogel template (ie, mostly collagen). For this reason, nanostructured HA has been an intriguing coating material on traditionally used titanium for improving orthopedic applications. In addition, helical rosette nanotubes (HRNs), newly developed materials which form through the self-assembly process of DNA base pair building blocks in body solutions, are soft nanotubes with a helical architecture that mimics natural collagen. Thus, the objective of this in vitro study was for the first time to combine the promising attributes of HRNs and nanocrystalline HA on titanium and assess osteoblast (bone-forming cell) functions. Different sizes of nanocrystalline HA were synthesized in this study through a wet chemical precipitation process following either hydrothermal treatment or sintering. Transmission electron microscopy images showed that HRNs aligned with nanocrystalline HA, which indicates a high affinity between both components. Some of the nanocrystalline HA formed dense coatings with HRNs on titanium. More importantly, results demonstrated enhanced osteoblast adhesion on the HRN/nanocrystalline HA-coated titanium compared with conventional uncoated titanium. Among all the HRN/nanocrystalline HA coatings tested, osteoblast adhesion was the greatest when HA nanometer particle size was the smallest. In this manner, this study demonstrated for the first time that biomimetic HRN/nanocrystalline HA coatings on titanium were cytocompatible for osteoblasts and, thus, should be further studied for improving orthopedic implants.

/pdf/biomimetic-helical-rosette-nanotubes-and-nanocrystalline-3aguxieprz.pdf

Biomimetic helical rosette nanotubes and nanocrystalline hydroxyapatite coatings on titanium for improving orthopedic implants

The objective of this study was to design a novel biocompatible and biomimetic composite based on the self-assembly of helical rosette nanotubes (HRNs) and nanocrystalline hydroxyapatite (HA) for improved orthopedic applications. Previous studies have shown that biologically-inspired HRNs can greatly enhance osteoblast (bone-forming cell) adhesion when coating titanium or embedding in hydrogels. In this study, HRNs were combined with hydrothermally treated nano HA as new nanocomposites. The nanocrystalline HA/HRNs have osteoconductive properties originating from nano HA, and also exhibit excellent biocompatibility by mimicking the nano HA/collagen structure. In addition, 2% nanocrystalline HA were well-dispersed in HRN hydrogels to serve as bone tissue engineering scaffolds with potentially improved mechanical and biocompatible properties. In short, the biomimetic HA/HRNs showed excellent cytocompatibility properties which makes them promising for various orthopedic applications (such as coatings on titanium, embedding into hydrogels as synthetic scaffolds, etc.)

/pdf/investigating-helical-rosette-nanotubes-and-nanocrystalline-12iaemjbb4.pdf

Jose Rodriguez

Papers

Biologically inspired rosette nanotubes and nanocrystalline hydroxyapatite hydrogel nanocomposites as improved bone substitutes

Biomimetic helical rosette nanotubes and nanocrystalline hydroxyapatite coatings on titanium for improving orthopedic implants

Investigating Helical Rosette Nanotubes and Nanocrystalline Hydroxyapatite as Novel Bone-like Biomaterials for Orthopedic Applications