Chapter 2 – Nanotechnologies for tissue engineering and regeneration

Stem cells (SCs) can self-renew or differentiate into different cell types, which makes them an ideal cell source for therapies based on tissue engineering. Despite these characteristics, the employment of SCs in clinics has seen alternating fortunes because of our limited understanding of the signals governing SC functions and fate, which impairs our ability to engineer systems to deliver SCs in vivo and to guide their correct biological processes. However, experimental evidence demonstrated that SCs are able to recognize biochemical and biophysical signals displayed by material surfaces; most importantly, cells integrate these signals to elaborate fate decisions. Although the mechanisms underlying signal recognition and response have not been thoroughly characterized, there is a general consensus that the cell adhesion process plays a central role. Adhesion represents a communication gate between exogenous signals and intracellular signaling cascades involving the cytoskeleton and the nucleus. In this work we present recent findings on materials engineered to control cell functions through adhesion processes. In particular, we emphasize the role of material signals on SC behavior. Finally, we discuss a few sensing and transductive molecular mechanisms in an effort to draw out unifying elements concerning cell recognition of and reaction to biophysical/biochemical material signals aimed at controlling cell fate through cell adhesion. Microneedles and nanomedicine are two out of several active innovative approaches used to enhance the transdermal drug and vaccine delivery. Their application individually or in combination have shown to be very promising and attracted considerable interest by researchers from both industry and academia over the last 2 decades. Combining the two technologies has growing interest and has shown to be promising approach not only in enhancing the transdermal drug and vaccine permeation for even difficult drug molecules, such as hydrophilic and macromolecules, but also impart protection and controlling the drug release rates. In Subchapter 2.2, we aim to highlight the advances, which has been made in using these two technologies as an individual or in combination with drug and vaccine delivery. Metal implants, in the form of screws, plates, or pins, are extensively used in the treatment of fractures and nonunions or as replacements for malfunctioned joints. These bones implants face many challenges for acceptance and survival upon insertion in the human body. These challenges include severe inflammation, bacterial invasion, and poor biointegration with the traumatized tissue. Titania (TiO2) nanotubes (TNTs) arrays engineered on the surface of Ti implants by simple and scalable electrochemical anodization process, which have been widely explored as a new nanoengineering approach to improve the process of osseointegration and at the same time to be used as depots for loading drugs and their controllable release for localized delivery, and therapeutic purpose. Several advanced functions can be introduced into these multifunctional implants, including biopolymers, nanoparticles or external stimulation (e.g., electrical, electromagnetic and ultrasound) to release the loaded therapeutic agents in a desired manner when required. Subchapter 2.3 highlights the developed concepts of drug releasing implants based on TNTs for enhancing osteogenesis at the bone-implant interface, as an alternative approach to systemic delivery of therapeutic agents. The reconstruction of skeletal defects is a continuing challenge. Bone and dentin are mineralized hard tissues. The primary inorganic component of these two tissues is crystalline hydroxyapatite and the primary organic component is type I collagen, and these two components are cell-manufactured materials. Tissue-engineering strategies using novel biomaterials have emerged as a promising potential for the treatment of mineralization defects. Some of the recent bioinspired biomaterials utilize proteins and peptides as nanoscale building blocks. A key functional property is that biomaterials need to be cell-compatible and mimic the dynamic nature of the extracellular matrix. ECM is a complex environment comprising a plethora of macromolecules. Another class of novel biomaterials that are currently being developed are peptide-based hydrogels. Peptide-based engineered scaffolds present several advantages over traditional protein scaffolds as the control over hydrogel properties and can be easily tailored to the requirement of the tissue. Biomaterials generated by the self-assembly process have varied applications as it mimics nature’s method of material synthesis. Therefore, concepts of protein-based self-assembly can be utilized for constructing useful biomaterials.