Nanoengineering Materials for Biomedical Uses

The rapid incorporation of nanostructures in regenerative medicine can be considered one of the biggest leaps in the production of novel materials for repair and regeneration of damaged tissues. However, despite a large number of articles published, clinical use of these materials is still in its infancy. The complexity and interdisciplinary nature of research aimed to repair damaged tissue and failing organs are the main limiting factors that have halted the progression for developing novel structures for tissue repair. In the present chapter, we revise fundamental concepts to be considered when designing technologies that will have to undergo scrutiny by regulatory agencies prior to being used in humans.

This chapter aims to provide a critical overview of available synthetic methodologies for engineered nanomaterials for biomedical uses. We cover different kinds of nanoparticles with a focus on examples that have proven biocompatibility. Also, we included a summary of techniques and procedures for nanoparticle characterization. Finally, we discuss the remaining challenges in the preparation of nanomaterials for biomedicine.

Although metallic nanoparticles have been applied in various fields of biomedical engineering research for quite some time, generating new biomaterials with improved regenerative capabilities remains the cornerstone in tissue engineering and regenerative medicine. These materials, once implanted in patients, will ultimately be invaded by endogenous cells, which emphasizes the relevance of surface composition as a critical factor in determining the regenerative potency of a given material. In this chapter, we present a brief revision on fundamental concepts and an up-to-date overview for surface characterization of nano-engineered structures.

Biomimetic nano-engineered materials have emerged as new potential additives for biomedical therapies. However, one of the most critical challenges that remain is the ability to produce responsive nanostructures that respond to external stimuli, enhance existing properties, and introduce new functionalities. In this regard, the use of computational methodologies to design, simulate, and visualize the interaction between biological substrates and nanostructures provides a powerful tool for better understanding structure/function. This chapter focuses on the use of molecular modeling and molecular dynamics (MD) methods to assist the design of bio-nanomaterials and characterize the structural aspects of the interaction between nanostructures and biological molecules. Computational simulations allow the analysis of the behavior of atoms and molecules for a period of time employing integrated mathematical and physical equations. Here, we describe how these theoretical methods are used to design and model nanomaterials in a rational way, as well as to evaluate its functionalization and association with drug-like compounds. Methodologies used in the field of computational nanotechnology include de novo modeling, parametrization, molecular dynamics simulations under functional conditions, binding free energy calculations, as well as future perspectives oriented to use reactive force field techniques.

Articular cartilage is the smooth layer of soft tissue that covers our bones and allows for the painless movement of our joints. Because of joint pathologies such as arthritis, cartilage can degrade over time in some individuals, causing them to live with considerable pain and reduced mobility. The high prevalence of arthritis and the absence of a cure for osteoarthritis, its most common form, have fueled sustained efforts to develop tissue engineering and regenerative medicine strategies aimed at regenerating cartilage. Despite a number of clinical advances that elicit cartilage repair, true regeneration remains elusive. Recent years have seen an increased use of nanoscale materials in the development of therapies for joint pathologies. Nanomaterials are comparable in scale to the principal building blocks of cartilage extracellular matrix, namely collagen and proteoglycan aggregates. Similarly, nanoparticles are sufficiently small to allow diffusion through the pores of the dense cartilage extracellular matrix and cell targeting. In this chapter, the organization of cartilage’s main building blocks will be reviewed from the nano- to macroscale, and sub-micron particles that participate in cell-cell communication will be highlighted. Efforts to design scaffolds incorporating cell-instructive nanoscale features and to tailor the mechanical properties, or even engineer spatial organization, in scaffolds for cartilage repair using nanomaterials will also be discussed. Finally, key design criteria in nanoparticle synthesis to enable targeted therapeutic delivery will be examined.

The skin is the largest organ in the human body; however, it is only a few millimeters thick. Among the main functions of the skin are to serve as a barrier for protection against physical and biological insults, as a thermal regulator to control internal temperatures, and as a sensor of physical stimulus that could lead to pleasant or harmful experiences. This highly-integrated sensory and regulatory armor is also capable of self-repair in response to injury, albeit the quality and extent of healing are determined by the skin condition and the type and size of the wound. In general, the wound healing process of skin comprehends four stages, which are hemostasis, inflammation, proliferation, and remodeling. These stages can be affected by internal physiological conditions and external environmental factors compromising the healing of the wound, for example, chronic wounds and bacterial infections. This chapter opens with an overview of the physiology of skin and skin wound healing. This overview is followed by a review of nanomaterial technologies and methods that have been investigated for the treatment of skin wounds. The chapter ends with an outlook of nanotechnology strategies for improving the treatment of skin wounds.

Nano-engineering materials-based diagnosis and treatment of central nervous systems (CNS) ailments has significantly advanced with our deepened knowledge of the pathophysiology of the blood–brain barrier. Unlike other nanoparticle-based tissue engineering strategies, the use of nanoparticles in the CNS must be specifically engineered to circumvent or penetrate the blood–brain barrier, which selectively inhibits drugs and nanoparticles from infiltrating. Current research in the field of CNS nanoparticles has future applications in the fields of diagnostic imaging, drug delivery, specific drug targeting, and tissue regeneration. This chapter highlights some of the nano-engineering of these promising nanoparticle-based biomaterials and their applications in the diagnosis and treatment of brain and spinal cord disease.

Herpes Simplex Virus-1 (HSV-1) infections in the eye often originate in the cornea before assuming a latent state in the trigeminal ganglion. During primary infection and upon injury or reactivation, HSV-1 can lead to significant corneal damage. Nanoparticles (NPs) are an emerging strategy for drug delivery to the cornea because they improve the long-term release of anti-HSV-1 drugs, such as nucleoside analogues. Acyclovir, ganciclovir, and valacyclovir have been successfully delivered using both polymer and lipid-based NPs in vitro. Solid silica dioxide NPs have been used to deliver the cathelicidin, LL-37, which prevented HSV-1 infection in corneal epithelial cells. Iron oxide nanoparticles have also been adapted to deliver an anti-HSV-1 DNA vaccine that successfully reduced corneal opacity and HSV-1 markers in a mouse model. Overall, NPs show promise as a delivery method for anti-HSV-1 strategies.

Cardiovascular disease is a leading cause of worldwide mortality. Despite the success of current therapies for acute myocardial infarction (MI), many patients still suffer irreversible damage, and the prevalence of heart failure is growing. After MI, the extracellular matrix (ECM) of the damaged myocardium is modified to produce scar tissue. This remodeling reduces the efficacy of therapies and also hinders endogenous repair mechanisms. Therefore, a strategy to prevent adverse remodeling and provide a suitable ECM environment that supports cells, tissue repair and functional restoration may lead to a superior therapeutic outcome in MI patients. Bioengineered materials are an attractive approach for achieving this. Herein, we review current research on materials that can act as a biomimetic matrix for supporting cellular repair in the post-MI heart. We also examine how nanomaterials are being used to treat the damaged heart. Finally, we provide an overview of the breakthroughs and limitations of biomaterial therapies for cardiac repair.

With nanomedicines increasing in market value and disruptive potential, a rapidly moving field such as this will require engaging in the difficult task of responsible management and the development of appropriate guidelines, which falls into the jurisdiction of governmental agencies. While each is influenced by the countries politics and demands of the people, there are shared goals of improving market success, risk assessment, and safety optimization. In this chapter, we describe the regulatory landscape with regards to nanomedicines in various countries. We first start with the world’s nanotechnological leaders in North America, the European Union, and Asian and then discuss the notable strides taken by emerging countries where nanomedicines have caught the public eye.