Frontiers in Biomaterials

Cationic polymers have been the subject of growing research interest in recent decades with new applications constantly appearing. They exhibit attractive physicochemical properties derived from the flexibility of the polymer chain, the formation of H-bonds, amphiphilic and electrostatic interactions as well as a great potential for being modified to obtain polymeric species for new applications. Furthermore, the different polymer architectures that are available include linear, branched and dendrimeric. According to their origin, cationic polymers can be classified in two general groups: natural or synthetic. Natural cationic polymers are interesting for therapeutic applications because they have generally a very good biocompatibility. Improvement in synthetic methods allows the preparation of cationic polymers with precise control of their properties and changes, such as the molecular weight distribution, polarity and the degradability of the chains if necessary. The reports describing antimicrobial, antioxidant, anti-tumoral and anti-inflammatory properties of cationic polymers have grown exponentially during the last years. Most of them also show interesting changes in their behaviors produced in response to stimuli such as pH and ionic strength. All these features make them even more promising for new biotechnological purposes. The wide range of uses of cationic polymers extends from industrial processes to a great variety of therapeutic, biomedical and pharmaceutical claims. In this chapter, we summarize the main properties and biotechnological applications of cationic polymers.

A main challenge for soft tissue regeneration is to develop products and therapies that minimize the fibrotic scarring characteristic of tissue repair. Scaffolds are three-dimensional structures in which cells can attach, grow and differentiate to form ex vivo or in vivo artificial tissue. They provide signals that trigger cell migration from the wound bed, as well as cell differentiation and cell secretion of extracellular matrix constituents. Scaffolds are made of natural or synthetic materials, with proteins from the collagen family being among the most used natural polymers. Collagen type I is a major component of the complex extracellular network of proteins that form the matrix of mammal tissues. Besides having cell-binding sequences, this protein is biodegradable, biocompatible, and exhibits a haemostatic effect when placed in open wounds. The aforementioned properties have made this compound a widely used natural material to produce scaffolds for tissue engineering skin and oral mucosa substitutes. This chapter reviews some of the parameters that influence the bioactivity of scaffolds emphasizing on collagen I scaffolds and their major applications in soft tissue engineering.

In recent years, there have been extensive developments associated with the application of natural, derivatized and semi-synthetic biopolymers for the localized and prolonged delivery of active pharmaceutical ingredients at the mucosal interface. Naturallyderived gums and mucilages are biomacromolecular assemblies employed for traditional (films and tablets) as well as advanced (nanomedicine and conjugated systems) bioactive delivery paradigms. These natural biomaterials are stable, easily available, economical, non toxic and associated with less regulatory issues as compared to their synthetic counterpart. Additionally, these biopolymers could be easily tailored via graft-polymerization, functionalization, conjugation, and polyelectrolyte formation in order to render specific properties such as mucoadhesivity. In this chapter, gums and mucilages along with their modified derivatives have been discussed accompanied by gums- and mucilages-derived mucoadhesive drug delivery systems. Additionally, the mechanistic phenomena dictating their mucoadhesive performance will be described with special reference to the constituent functional groups and their role in muco-tethering and -penetration. A representative list of gums and mucilages include, but not limited to, alginic acid, agar, carrageenans, and laminarin (marine origin); gum arabic, gum karaya, locust bean gum, gum ghatti, khaya gum, tragacanth, albizia gum, guar gum, starch, cellulose, larch gum and pectin (plant origin); and curdian, pullulan, xanthan, dextran, zanflo, emulsan, Baker’s yeast glycan, lentinan, schizophyllan, scleroglucan and krestin (microbial origin).

Recent developments in polymer technology have created new opportunities for ocular drug delivery, which has unique challenges due to specific attributes of the eye. The unique requirements of ocular drug delivery pose several difficulties for a formulator to select an appropriate polymer and use it in ODD. Nanotechnology has opened up new vistas as the nano particle becomes a choice of drug delivery in ODD. Layers of tissue, blood barriers, choroidal flow, lymphatic drainage, and lacrimation are some of the factors that limit therapeutic concentrations of drugs from reaching diseased parts of the eye. Currently, research is being directed towards the identification and discovery of novel drug delivery systems using newly introduced polymers, nanoparticles, liposomes, and adhesive gels to circumvent barriers and obtain sustained levels of therapeutics at target ocular sites. The ocular route of drug delivery is determined based on disease application and each method presents its own challenge: topical (uveitis, conjunctivitis), systemic (cytomegalovirus retinitis), intravitreal (macular degeneration, diabetic reinopathy), subconjunctival (glaucoma), subtenon (retinal vein occlusion). Formulation factors such as drug loading, drug stability, drug excipient interaction, carrier biocompatibility and drug carrier biodegradability need to be considered when designing ocular drug delivery systems. Ocular biocompatibility and ocular biodegradability are one of the few important characteristics which dictate the selection of such polymeric materials to be used as ODD carriers. This chapter covers various aspects of the ocular delivery and discusses the characteristic of the nano biomaterials to be used as ocular drug delivery carriers.

The technological revolution which is smart biopolymers illuminates the propensity of certain multifunctional materials - shape biopolymers - to change form and move on exposure to a stimulus, and in so doing, perform functions which furnish them with a range of capabilities. Thus, the mechanized uniqueness of these polymers is embodied not only in their macroscopic structural changes, but in their reversible shape change. There is a binary classification of shape biopolymers: shape-memory and shape-changing biopolymers. The focus of this chapter is on shape-memory biopolymers (SMBPs), which possess dual-shape competence. In terms of biomedical applications, SMBPs could have diverse applications in stimuli-sensitive drug delivery systems, intelligent medical and surgical devices, tissue engineering, or implants for minimally invasive surgery. In this chapter, we firstly elaborate on the fundamental molecular mechanisms culminating in the macroscopic dynamics of shape-memory systems bringing about their pertinent action and the recovery of their original shape. Further, we highlight the diverse stimuli instigating the polymeric response such as thermal stimuli, light, magnetism, mechanical stress or moisture. In addition, we discuss the biopolymers exhibiting potential shape-memory capabilities, as well as various modifications, functionalizations and reinforcements to these to customize their biomedical applications. An expert summation of the application of these biopolymers in the design of smart delivery systems, implants and devices, as divulged through recent investigations, is presented. The chapter culminates in current and future trends in the design and application of SMBPs and their overall potential benefits.

The porous textile fabrics as scaffolds combining with extracellular matrix proteins (e.g. fibronectin, collagen etc), and living cells give a possibility to develop biological tissues for human body repair, such as organ transplants. The flexible biotextiles act as scaffold materials to provide support for cell adhesion, growth and proliferation. A key requirement for an artificial implant is to exactly mimick the biological and mechanical functions of an injured tissue or organ to be replaced without evoking an immune response from the host. Due to their easily tunable properties, the “weak” textiles, such as nonwoven, woven, knitted structures, braided structures etc, are promising candidate for tissue engineering applications. These structures provide compliance, porosity and 3D microstructure to induce cell attachment and proliferation to regenerate complex tissues. In this chapter, scaffold designing in tissue engineering using textile structures has been reviewed. The chapter elaborates on 3-D fabric (woven, knitting, nonwoven etc.) and their composites for designing scaffolds with required mechanical and biological properties.

Development of hydrolytically or enzymatically labile bonds is an on-going process in connection to biomaterials. Synthetic biodegradable polymers such as polyhydroxy acids (PHAs), which include homo as well as copolymers of polylactic acid (PLA) and polyglycolic acid (PGA), are inexplicably used in drug delivery and tissue engineering applications. Adjusting the ratio of constituting architecture of block copolymers to manipulate amphiphilic behavior and chemical as well as physical properties is the prime methodology adopted for tailoring PHAs suiting specific requirements. It is critical to develop three dimensional porous scaffolds with enhanced cell adhesion characteristics for improved tissue regeneration while ‘modified’ release of payload is essential in novel targeted drug delivery systems. Combinatorial polymeric architectures composed of synthetic and naturally derived components aid in attaining these prerequisites by providing surface functionalities, optimal hydrophobic-hydrophilic ratio and flexibility of support. Synthesis of ‘tailored’ natural and synthetic biodegradable copolymers is the thrust research area making use of advantageous properties of both individual components for creating a unique structural analogy mimicking biological world. Biomaterials created solely from natural polymers such as polysaccharides and proteins find many uses as drug delivery carriers and ‘grafts’. However, they are mechanically weak, their integration with PLA and PGA considerably improve mechanical strength while retaining higher cell adhesion capabilities.

The present chapter details combinatorial approaches for the generation of large arrays of biodegradable polymeric materials entailing multitudes of components to meet their desired properties. Novel synthetic methods generating varied hybrid polymeric products like sponges, meshes, microspheres and nanoparticles are discussed.

The environment represents the major source of prokaryotic (Eubacteria and Archaebacteria) and eukaryotic (fungi, algae and phytoplankton) microorganisms that can posses the ability to synthesize various microbial exopolysaccharides. Since the mid-19 th century, when the dextran was found in the wine, the microbial exopolysaccharides have received a growing attention due to their structural diversity that can supply a broad range of physico-chemical, rheological and biological properties. Exopolysaccharides, known as extracellular polysaccharides because they are secreted outside of the cells, are high molecular weight polymers, that can be classified depending on the monomeric composition into two groups: homopolysaccharides composed of a single type of monosaccharides (dextran, levan) or heteropolysaccharides formed from two or more repeating units of monosaccharides (xanthan, gellan, alginate and hyaluronic acid). Also, microbial exopolysaccharides are produced in two basic forms: capsules and slime polysaccharides. Industrial and technological advancement has led to the use of the exopolysaccharides in various fields such as, food industry, waste water treatment, bioremediation as well as in the pharmaceutical and biomedical fields. Antiulcer, antitumor, anticoagulant and antiviral activities, anti-reflux therapies, cholesterol lowering agents, surgical and ophtalmic applications, treatment of rheumatoid arthritis are some of the health benefits of exopolysaccharides. The objective of this chapter is to make in introduction a concise presentation of the structure and properties of the most popular exopolysaccharides such as, dextran, curdlan, pullulan, xanthan gum, gellan gum, hyaluronic acid and alginate followed by a discussion about their applications for treatment and prevention of some diseases.

Environmentally responsive or smart biomaterials have emerged as an answer to the pursuit and growing need for efficient bio-mimicking stimuli responsive systems. Their efficiency resides in the ability to sense a given perturbation in the biological environment through interfacial interaction and respond intelligently, as per biological need, through switching of their physicochemical properties. The distinct environmental changes that could trigger such responses include a change in temperature, pH, ionic strength, light, electric and magnetic field. Polymers with the plethora of possible chemistry provide a drive for exhaustive exploration and are therefore the focal of environment responsive biomaterials. Advancement in chemistry combined with biology provides a better approach to synthesize novel polymers, incorporating functionalities and developing supramolecular architectures which can impart new bio-interfacial properties. The leading avenues of environmentally responsive polymers application are tissue engineering, regenerative medicines, integrated bio-sensors, drug delivery and multi-responsive materials but are not limited to them. Development of single, dual or even multifunctional materials can be possible through appropriate design, synthesis method and the combination of the building blocks. The chapter reviews an array of polymeric materials responsive to internal stimuli with key insight into the recent strategies employed for their synthesis and modification for specific biomedical application. The chapter further presents a close discussion on the interfacial characteristics of these polymers that enable reversible switching of physicochemical properties in response to different environmental cues prevailing in a biological system.

Providing cyto and, biocompatible, biodegradable, permissive, elastic and, three-dimensional extra-cellular microenvironment with bio-mimicking capabilities is a daunting challenge in contemporary tissue bioengineering. The ability to guide cell differentiation and proliferation with adequate adaption to the desired functional tissue or, organ forming with positive affinity for extracellular support in regeneration and, enough spatio-temporal feasibility for newly constructs and advancing cell mass are amongst the most desirables towards producing functional bioconstructs in the modern tissue bio-engineering realm. The scaffold providing extracellular microenvironment with its desired porosity and surface properties is the main driving force that primarily influences the cell bio-engineering outcomes. The physical factors at the localized cellular microenvironment, individual cell’s shape with the overall cellular-mass geometry at its generation and, propagation stages, biomatrix’s response(s) and interfacial interactions feasibilities between the biomass and the extracellular matrixsupport platform along with the molecular recognition capabilities on both sides with the involved and, mutually related bio-mechanics as well as intra-entities environmental forces of physico-mechanical nature and, the surface specifications of the matrixsupport, be it the nano or micro-topographical features of the extracellular supportmatrix or, the force(s) responsible for interplay among various factors causing cellular and sub-cellular level contractions are very important and crucial deciding factors in preparative-designs and outcomes of the tissue bioengineering matrix support platform. The external resisting factors originating from the support matrix constituting the extracellular microenvironment with potent growth-factors mediated signaling as well as presence of nutrients, biochemicals, gases and their diffusions have, at all times, impacted very strong influences on regulating the overall cell-fate in the extracellular microenvironment towards generating the desired biomass. Various matrix-support or the scaffolds for encompassing the extracellular microenvironment have been developed. These materials are far from perfect or practical enough for various characteristically defined outcomes, hence fewer types of scaffold materials fit for majority of functional characteristics. Several bioengineering tools and, nano and micro-scale specifications laden entities, materials and, devices of biomaterial and synthetic origins are being employed successfully to develop scaffold and its materials to fulfill the essentials in tissue bioengineering domain towards producing various bioconstructs and tissue types by providing desired scaffold. The employed, natural or synthetic, molecular devices, materials and chemical entities, mostly polymeric in nature, with proven intrinsic properties and extrinsic physical factors significantly playout in practical tissue-engineering situations recapitulate the critical biochemical and biophysical aspects of the developing cell types in the generated extracellular microenvironment for desired tissue bioengineering constructs outcomes through the environment of the scaffold. Some of these materials, entities and devices in-use now include bio-compatible polymeric hydrogels, single and, composite synthetic and natural polymeric materials in random or, designated/patterned formations or, in layered/arrayed scaffoldings, the nanofibers, semi and fully-lithographed polymeric material devices, proteins, polypeptides, antibiotic-based hydrogels as well as scaffolds produced through a variety of techniques including photo-reactivity with their inherent specifications for producing the intended scaffold are worth mentioning.

Emulsions and suspensions are systems formed by at least two phases; one of them dispersed into another. For their preparation these generally unstable structures require the addition of extra molecules that improve either their thermodynamic or kinetic stability. Traditionally small amphiphilic molecules have been used for this purpose. More recently, the surface and rheologic properties of biopolymers have been modified in order to “tune” their properties as to improve emulsions and suspensions stability.

Most of the research and technological developments related to emulsions performed so far imply water as one of the involved phases. Non-aqueous, oil-in-oil, anhydrous or waterless emulsions, are common names for the dispersed systems in which water is absent. Even though the first reports in this subject were published around 50 years ago the literature on this area is sparse. In the recent years, non-aqueous emulsions became attractive as potential vehicles for the development of drug delivery systems and healthier foods. This led to the design of novel and simpler methods for the dissolution of polymeric surfactants into edible vegetable oils and improved dispersion of nonaqueous phases into structured oils giving a result very stable non-aqueous emulsion with tunable rheological properties. These emulsions have potential applicability to improve nutritional qualities of foods as well as to design vehicles for hydrophobic active pharmaceutical ingredients.

In this chapter, we will summarize the recent advances in the basic principles involved in biopolymer stabilization of non-aqueous emulsions and their potential applications for the design of foods and medicines with improved performance.

Developing new neuropharmaceuticals presents formidable economic, scientific and medical challenges mainly due to the complex nature of the central nervous system (CNS), in particular the blood-brain barrier (BBB). The constituents of the BBB and its drug efflux system form some kind of a boundary which prevents the entry of potent neurotherapeutics from entering the brain thus leading to treatment inefficiency for various CNS diseases. Conventional neurotherapeutic interventions for major disease conditions include among others, ablative limbic system surgeries, vagus nerve stimulation, transcranial magnetic stimulation and deep brain stimulation. These interventions are however somehow invasive. The progress so far made in the area of interventional neurology has greatly widened the scope of viable pharmaceutical drug delivery systems for which biopolymers may play a substantial role. The major aim is to improve specificity in drug delivery (e.g. through drug targeting) and to avoid or reduce the adverse effects imposed by the conventional neurotherapeutic interventions. This Chapter therefore seeks to provide a detailed discussion of the potential application of biopolymers in neurotherapeutic interventions citing most the: i) strategies for neurotherapeutic interventions (including biopolymer gene-based drug delivery, bioactive release from nerve conduits, nonviral gene delivery vectors, molecular imaging as a novel technique for biopolymer-based neurotherapeutic intervention); and ii) biopolymers used in neurotherapeutic interventions (including biopolymeric vehicles, biopolymer scaffolds, multiple polymer-based layers, polysaccharide-based biopolymers, protein-mimicked polypeptides and protein-based biopolymers). Finally, this Chapter seeks to provide a detailed description about the future prospects for biopolymer-based neurotherapeutic interventions.

Metallic biomaterials can be described as substances that do not contain drugs or active pharmaceutical ingredients, are natural or artificial in nature and are based on metallic elements or metallic alloys which are usually applied as a whole or part of biological systems and perform, amplify or substitute a function that has been lost through injury or illness. They can be used for an undefined duration in different spheres of patient health care such as medicine, surgery, dentistry and veterinary medicine. This chapter reviews the porous and non-porous structured class of metallic biomaterials, their desirable physicochemical and physicomechanical properties as well as their various types, fabrication methods and biomedical applications.

The industrial demand of natural polysaccharides or their chemically modified derivatives have increasing due to their safety, biocompatibility, non-toxicity and biodegradability. Modified polysaccharides are industrially acceptable as disintegrating agent, thickening agent, gelling agent foam stabilizer, swelling agent, emulsifying agent, encapsulating agent, binding agent, etc. In addition, biopolymers are acceptable as materials for nanoparticles for clinical application. This is due to their versatile traits, including biodegradability, biocompatibility and low immunogenicity. These tailor-made materials are now commercially available and thus can give competition to already available synthetic excipients. Considering the current needs to produce stable nanoparticle systems, the chemical modification of these polysaccharides further improves their physicochemical as well as mechanical properties. The attempts have been made to obtain nano-carrier for therapeutic purposes and with their variation in materials and process preparation. This chapter is aimed at discussing the application of these modified polysaccharides with their physico-chemical characterization. Further, the factors influencing these process variables taken care off while making them are also enlightened in addition to influence of modifying polysaccharides on the drug release properties of pharmaceutical dosage forms and for other purposes in pharmaceutical industry.