Advances in Biomaterials for Biomedical Applications

Polymer blends and nanocomposites are widely explored for different biomedical applications such as biodegradable scaffolds, biosensors, implants and controlled drug release. Both, synthetic and semi-synthetic polymers are used in medical applications and have their inherent advantages and disadvantages. Synthetic polymers offer flexibility of varying monomer unit, molecular weight, branching and thus offer a diverse set of physico-mechanical properties, whereas natural polymers offer superior biocompatibility and biodegradation profile. Availability of polymer blending techniques adds another dimension to the property set that polymers can offer, and therefore polymer blending is often used to tailor biodegradability and physico-mechanical properties. Polymers, in general, have poor mechanical properties when compared to metals and ceramics, putting a load bearing limit on polymer-based medical implants. The addition of reinforcing/functional filler is expected to overcome such disadvantages of polymers. Polymers composites are heterogeneous systems wherein polymers are compounded with micron or nano-size particles to render high strength, electrical conductivity or any other functional attribute. This chapter describes the technological aspects of polymer blends and nanocomposites with a specific reference to synthesis, characteristics and applications of multi-phasic polymer systems as implants, scaffolds, and controlled drug release matrices. A detailed account of synthetic and natural polymer nanocomposites along with a brief discussion on important nano-fillers used in medical applications and interface modification techniques is presented. Few examples of recently explored novel polymer blends and composites that displayed promising properties as implants, scaffolds, biosensors and control release matrices have also been discussed.

Polyelectrolytes are a class of macromolecules which spontaneously acquire a net positive or negative charge when dissolved in an appropriate polar solvent such as water. Polyelectrolytes can co-react in aqueous solutions and form polyelectrolyte complexes (PECs) or polysalts, which resemble general self-assembly processes. It is believed that PECs are formed due to increase in entropy, caused by the liberation of low-molecular-weight counter ions. PECs can be classified into three types: soluble, colloidally stable, and coacervate complexes. Depending on the compatibility between the reacting polyelectrolytes, the electrostatic interaction between the anionic and cationic groups is stronger than most secondary interactions. Hence, this avoids the use of various chemical cross-linking agents, which reduces the possibilities of toxicity and other harmful effects that may be caused by the agents. PECs combine unique physicochemical properties, which are different from those of the individual components. These find a wide range of applications, such as membranes, as coatings on films and fibers, and as microcapsules for drug delivery, to name a few. PECs have immense potential uses in the field of ecology, biotechnology, medicine, and pharmaceutical technology.

Application oriented selection of a material depends on the bulk properties of that material. However, a first encountering feature of any material in an application is its surface and thus material’s surface is one of the foremost parameter that decides the fate of material performance. Modulating the surface properties is considered as a potential approach to meet the application requirement. In past, various techniques (like, chemical, γ-irradiation, mechanical abrasion) have been developed for the surface modification of materials. These methods have certain disadvantages, like chemical treatment involve the disposal of polluted solvents/water in the environment, whereas other techniques may affect bulk properties of the material. Since three decades, plasma surface modification technique has attracted attention of scientists and technologists for creating new surfaces for various end-use applications such as textiles, food packaging, coatings, medical devices etc. Especially, low temperature plasma (low pressure and atmospheric pressure glow discharge) has attracted for its potential application in the new biomedical devices and biomaterials development. Plasma processing has proved itself a very promising and potent technology for modification of surface properties in an effective, environment friendly and economical way for converting low cost materials into a value added materials. The surface properties and biocompatibility can be enhanced selectively and precisely without affecting material’s bulk properties by the use of plasma surface modification technique. This chapter is providing a brief overview of low temperature plasma as a versatile technology for surface modification and its application pertaining to biomedical materials research. Various inferences are also drawn from the types of plasma used in the biomedical applications.

Use of biomaterials in autoimmunity research is widely explored, as an adjuvant to induce antigen specific immune responses, for facilitating induction of experimental models to study disease pathogenesis and for designing novel therapeutic targets. Similarly, polymeric biomaterials are explored as a delivery vehicle for sustained and specific release of auto-antigens/drugs to treat autoimmune disorders. Although considered as biocompatible, implantation/injection of polymers like silica and metallic implants are associated with development of chronic inflammation and autoimmunity. Despite these compatibility concerns, biomaterials are still considered as favorable materials for several applications in the autoimmunity field.

Tissue Engineering consists of cells, a scaffold and cytokines. Decellularization represents the removal of cells from tissues or organs. Recently, decellularized tissue has been investigated as a scaffold for tissue engineering, termed decellularized tissue engineering. Importantly, the decellularized organ retains its original structure, which is then used as a template for organ construction. The decellularized organ also retains the tissue-specific extracellular matrix. Therefore, decellularized tissue can be used as a matrix to provide a suitable microenvironment for inoculated cells. Based on these concepts, the reconstruction of tissues/organs with decellularized tissue/organ has been attempted using decellularized tissue engineering. In this chapter, we introduce the typical methods used, history and attainment level for the reconstruction of specific tissues/organs. First, the different decellularized techniques and characteristics are introduced. Then, the commonly used analysis methods and cautionary points during decellularization and reconstruction with decellularized tissues/organs are explained. Next, the specific methods and characteristics of decellularized tissue engineering for specific tissues/organs are introduced. In these sections, the current conditions, problems and future work are explained. Finally, we conclude with a summary of this chapter.

With the advances of stem cell research, development of intelligent biomaterials and three-dimensional biofabrication strategies, highly mimicked tissue or organs can be engineered. Among all the biofabrication approaches, bioprinting based on inkjet printing technology has the promises to deliver and create biomimicked tissue with high throughput, digital control, and the capacity of single cell manipulation. Therefore, this enabling technology has great potential in regenerative medicine and translational applications. The most current advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this chapter, including vasculature, muscle, cartilage, and bone. In addition, the benign side effect of bioprinting to the printed mammalian cells can be utilized for gene or drug delivery, which can be achieved conveniently during precise cell placement for tissue construction. With layer-by-layer assembly, three-dimensional tissues with complex structures can be printed using converted medical images. Therefore, bioprinting based on thermal inkjet is so far the most optimal solution to engineer vascular system to the thick and complex tissues. Collectively, bioprinting has great potential and broad applications in tissue engineering and regenerative medicine. The future advances of bioprinting include the integration of different printing mechanisms to engineer biphasic or triphasic tissues with optimized scaffolds and further understanding of stem cell biology.

Delivery of efficient and safe gene transfer vectors capable of achieving appropriate levels of therapeutic gene expression into the target place is a very valuable strategy for articular cartilage repair. Diverse nonviral and viral gene vehicles have been studied to modify relevant cell populations involved in cartilage regenerative processes, among which the nonpathogenic, effective, and relatively safe recombinant adeno-associated viral (rAAV) that have emerged as the preferred gene delivery system to treat human disorders. The clinical adaptation of these systems is still limited by several hurdles including the presence of immune and toxic responses in the host organism, the ubiquity of rate-limiting steps associated with physiological barriers, and the possibility of dissemination to nontarget sites that may impair their therapeutic action. The use of controlled release strategies to deliver gene transfer vectors such as rAAV may provide powerful tools to enhance the temporal and spatial presentation of therapeutic agents into a defined target and overcome such obstacles in vivo. The goal of the present work is to provide an overview of the most recent advances in gene therapy approaches for cartilage repair based on the use of adapted biomaterials as controlled delivery platforms of gene transfer vectors to improve the efficiency of the therapeutical transgene.

Tissue engineering aims to gain mechanistic insights into human diseases and to develop new treatment protocols. Although 2-dimensional (2-D) flat petri dish culture and in vivo disease-based models are the industrial gold standards for understanding the underlying disease pathophysiology and for drug screening/testing, they are associated with certain limitations. While the 2-D cell culture systems fail to mimic in vivo signaling, animal-based disease models are associated with long incubation period, high cost, ethical constraints as well as depiction of human pathology in different species. Therefore, there has been a paradigm shift towards the development of 3-dimensional (3-D) based in vitro disease models. These models act as bridging gaps between the aforementioned conventional strategies thereby fastening clinical translation. In this regard, biomedical engineering plays a key role towards the development of tissue engineering based 3-D disease models. These models have demonstrated success in recapitulating human diseases in terms of in vivo morphology and signaling. This chapter will present examples of biomaterials-based 3-D engineered disease models with a focus on cancer.

Regenerative medicine uses cell alone or in combination with carrier to deliver at the required site for restoring the normal functions of diseased or degenerated tissue. Various strategies to restore tissue functions involve specific cell types, scaffolds and delivery processes that are still in developmental stage. Obtaining sufficient quantity of cells by non-invasive approach for the application in regenerative medicine is still a challenge. Pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells (iPSCs), possess the inherent ability of self-renewal and differentiation into many cell types. In particular, iPSCs are of a special interest because patient-derived iPSCs have the ability to reproduce patient-specific clinical conditions. The development of manufacturing systems for PSCs, including cell culture engineering, is a challenging research field for the clinical application of PSCs such as in regenerative medicine. One of these manufacturing systems uses magnetic nanoparticles which are well known for their application in magnetic resonance imaging and magnetic hyperthermia. Besides, this chapter is focused on the basics of magnetic nanoparticles, its functionalization and further applications of a magnetic force-based cell manufacturing system for pluripotent stem cells. Indeed, we have developed a procedure in which cells are labeled with magnetite cationic liposomes via electrostatic interaction between the positively charged liposomes and the target cells. The culture system may provide a useful tool for studying the behavior of PSCs and an efficient way of PSCs manufacturing for clinical applications.

Fluorescent gold nanoclusters (AuNCs) comprising of several to tens of atoms with a dimension comparable to the Fermi wavelength of electrons have attracted greater attention in chemistry and medicine for the past decade due to their high fluorescence, good photostability, non-toxicity, excellent biocompatibility and water solubility. Green synthesis of AuNCs provides excellent possibilities to use them as biocompatible tools for fluorescent imaging, targeted therapy and have been extensively used in many fields of oncology. Biomolecules or functional molecules capped AuNCs could be further modified by conjugating targeting moieties and therapeutic molecules which allow active targeting, imaging and drug delivery at the tumor site. The current book chapter mainly focuses on the recent reports including mechanism of fluorescence, various synthesis strategies, bioconjugation and application of AuNCs for precise diagnosis and treatment of cancer.

The major breakthrough of graphene in 2004 has paved the way for various approaches to synthesize graphene and its derivatives for biomedical applications. With the interest in graphene as a cargo in drug delivery, the exploration has slowly shifted to metal-graphene materials as fluorescent probes. Metals such as Cu, Au, Fe, Ce and etc., have been incorporated into graphene for various applications such as sensing and imaging. With the success of graphene—metal nanoparticles (NPs), its more recently discovered counterpart, graphene—metal nanoclusters (NCs) has gained much interest lately. Loosely defined, NCs are a cluster of NPs with sizes of 1–20 nm with a narrow size distribution, which endows it with unique electronic properties compared to metal NPs. NCs are size-dependent fluorescent materials with good photostability. They have been largely investigated in biosensing, diagnosis and therapy applications, a term coined as theranostics. In more recent applications, graphene metal NCs were stabilized with protein biomarkers for targeted sensing of cancer cells and diseases. Smart delivery system allows diagnosis, imaging and targeted therapy simultaneously. This chapter focusses on the synthesis and biomedical applications of graphene—metal NCs with a detailed discussion on their properties and applications in the biomedical field. A brief description on the toxicity is addressed as well, together with future considerations for possible applications of graphene—metal NCs clinically.

Around the globe, there is a great concern about controlling growth of pathogenic microorganisms for the prevention of infectious diseases. Moreover, the greater incidences of cross contamination and overuse of drugs has contributed towards the development of drug resistant microbial strains making conditions even worse. Hospital acquired infections pose one of the leading complications associated with implantation of any biomaterial after surgery and critical care. In this regard, developing non-conventional antimicrobial agents which would prevent the aforementioned causes is under the quest. The rapid development in nanoscience and nanotechnology has shown promising potential for developing novel biocidal agents that would integrate with a biomaterial to prevent bacterial colonization and biofilm formation. Metals with inherent antimicrobial properties such as silver, copper, zinc at nano scale constitute a special class of antimicrobials which have broad spectrum antimicrobial nature and pose minimum toxicity to humans. Hence, novel biomaterials that inhibit microbial growth would be of great significance to eliminate medical device/instruments associated infections. This chapter comprises the state-of-art advancements in the development of nano-antimicrobial biomaterials for biomedical applications. Several strategies have been targeted to satisfy few important concern such as enhanced long term antimicrobial activity and stability, minimize leaching of antimicrobial material and promote reuse. The proposed strategies to develop new hybrid antimicrobial biomaterials would offer a potent antibacterial solution in healthcare sector such as wound healing applications, tissue scaffolds, medical implants, surgical devices and instruments.