The kidneys are responsible for the continuous filtering of toxins and metabolic byproducts from blood, as well as for critical metabolic regulatory functions, including bone homeostasis and red blood cell synthesis. High-impact kidney diseases such as acute renal failure and end-stage renal disease are commonly treated by conventional therapies such as hemodialysis, hemofiltration, or hemodiafiltration. These therapies provide for water/solute balance and toxin removal but fail to replace metabolic regulatory functions of the cellular elements of the kidney. Due to shortages of donor kidneys for transplantation, there is a need to develop advanced therapies to more effectively treat kidney diseases. Approaches using renal cell therapy, microelectromechanical systems, and advanced membrane materials are in various stages of development, and are promising advances as they transition to clinical therapies.
Total joint replacement is one of the most effective treatments for arthritis. Bone cement revolutionized the fixation of artificial joints. This chapter presents an overview of the mechanical properties and behaviors of poly(methyl methacrylate) bone cement. The success of a cemented artificial joint depends on the integrity of the bone cement, which, in turn, depends on the mechanical properties. The factors that affect the mechanical properties can include those internal to the bone cement, such as the chemical formulation or type of radiopacifier, and those external to the bone cement, such as mixing technique and initial temperature of the components. In this chapter, we review not only the investigations to measure the properties, but also the efforts to change and improve bone cement. The success of cemented total joints may be improved by improving the mechanical reliability of the bone cement.
Since the 1990s, carbon nanotubes (CNTs) and related nanostructures have inspired the engineering, scientific, and medical communities to utilize their novel characteristics and superior properties in a variety of applications. Carbon nanostructures can help strengthen materials and composites, further miniaturize electronics, and enable more efficient green energy technology. Many of the exciting possibilities of carbon nanostructures exist in sensing applications, where their unique properties can be applied to improve the detection of biological threats, efficiently and compactly monitor environmental conditions and screen the health of patients, and detect the early onset of disease. Carbon nanostructures come in a variety of sizes, shapes, and configurations, which make them well suited for a broad range of sensing applications. This chapter focuses on the development of several CNT-based sensing platforms and recount the current utilization and application trends in biological sensing.
End-stage renal disease (ESRD) is a devastating condition, which involves multiple organ systems in affected individuals and requires renal replacement therapy. Currently, the gold standard treatment for this condition is renal transplantation, which can restore complete kidney function. However, renal transplantation is limited by the critical shortage of transplant organs as well as complications that can result from chronic immunosuppressive therapy and graft failure. Physicians and scientists are now turning to the fields of tissue engineering and regenerative medicine to develop alternative treatment modalities for ESRD. The kidney is a complex organ containing multiple cell types and an intricate functional anatomy that renders it one of the most difficult to reconstruct. Developmental approaches to kidney regeneration that are based on the embryology of the kidney are being studied and have shown promise. In addition, recent advances in cell technologies, including the identification of putative renal progenitor cell populations, have allowed for the development of novel cell-based approaches for kidney tissue regeneration. Efforts to identify reliable cell sources, develop ideal growth environments and innovative differentiation factors, and discover synthetic and naturally derived materials for use as an ideal support structure for tissue regeneration are ongoing. However, numerous challenges must still be overcome in order to translate these techniques into clinically relevant therapies.
Tissue engineering research revolves around the biomaterial scaffolds, cell sources, in vitro constructs, and in vivo integration into living hosts. These components of tissue engineering are independently developed and optimized for specific applications with relatively simple structure–function relationships are relatively simple. High-throughput screening tools have been employed recently to further identify suitable parameters of the components for applications that require more detailed and tighter coupling of structures and functions. These screening approaches also enable systematic characterizations of biological responses in vitro and in vivo, across different size scales from molecules to tissues. Though, high throughput and individual components are still optimized independently mainly due to the lack of quantitative models linking the components together into a functional process; for example, little is known on how biomaterials, cells, or even carefully designed constructs would behave when integrated into living hosts. We analyze the current status of the discrete and high-throughput component-based approaches; and propose new process-centered approaches that would integrate components with the help of computational modeling such that future biomaterials and tissue engineering research will be less trial and error but more based on rational-design. Systems biology will play a key role in driving future applications in regenerative medicine.
At the time of the description of ‘osseointegration,’ dental implantology started from the rehabilitation of ‘simple’ edentulous jaw with the aim of anchoring prosthesis. The focus has now shifted to a functional and esthetically stable rehabilitation in nearly every indication. Cp titanium was favored the last years, whereas recently new alloys with higher strength have been developed with the clear aim to avoid augmentation procedures and allow the use of smaller dimensioned implants. Also, zirconium oxide ceramic with better esthetic properties is within the focus of science. Macrostructures have been investigated using finite element modeling, animal models, and clinical studies with the focus on high primary stability and a long-term stable crestal bone level. This has lead to the introduction of stable (conical) implant abutment connections with a slight difference in the diameter (platform shift). A variety of data is available on optimization of the implant surface to allow faster osseointegration (secondary stability) and give the chance for immediate or early loading of the implants in the clinical situation. A promising future goal seems to be the idea of biomemetic coatings of the implant surface either using nanoparticles or growth factors. The integrity of the soft tissue abutment connection also has some potential for scientific research with the aim to avoid peri-implant infection by using either improved surfaces of the abutment or antibacterial properties.
Musculoskeletal injuries and degenerative conditions constitute a bottleneck in the healthcare system. Tissue grafts and scaffolds, based on extracellular matrix (ECM) molecules, have received much attention as they closely imitate the structural, biochemical, biophysical, and biological properties of the tissue to be replaced. This chapter summarizes the most abundant ECM components that are used in tissue-engineering applications for bone, intervertebral discs, and tendon.
For native cardiac tissues and their tissue-derived biomaterial and engineered tissue counterparts, there exist many physiological, surgical, and medical device applications where rigorous biomechanical models are required. However, particular challenges are encountered in constitutive modeling for cardiac tissues and their engineered tissue counterparts due to their complex mechanical behavior. For example, because of their oriented fibrous structures, they often exhibit pronounced mechanical anisotropy. In addition, they exhibit highly nonlinear stress–strain relationships, large deformations, viscoelasticity, and strong axial coupling. On the whole, cardiac soft biological tissues defy simple material models. In addition, the constituent fibers can undergo large rotations and exhibit nonlinear stress–strain behavior that can induce complex behaviors at the macrospecimen scale not easily accounted for in classic material models. Accounting for these behaviors in both experimental evaluation and formulation of appropriate constitutive models continues to be a challenge. The focus of this chapter is to review current approaches and discuss future trends.
Protein-engineered biomaterials are designed and synthesized using recombinant protein technology and offer an alternative to both harvested natural biomaterials and synthetic polymeric biomaterials. A defining feature of such protein-engineered biomaterials is the precise control over macromolecular composition and function, made possible by modular peptide domain design and exact specification of the encoding DNA sequence. This approach allows multiple functional domains to be encoded directly into the protein backbone, creating a plethora of biomaterials with tunable mechanical, biochemical, and biodegradation properties. This chapter describes the design, recombinant synthesis, and fabrication strategies for protein-engineered biomaterials for use in tissue engineering applications. Analytical tools for characterizing the molecular and bulk properties of these materials are also discussed. Building upon modular domain design and by expanding peptide functionality, a variety of protein biomaterials have been engineered which serve as versatile platforms for studying and addressing various challenges in regenerative medicine.
Although protein adsorption to biomaterial surfaces is widely recognized as being an important mediator of biological response, a molecular-level understanding of protein–surface interactions is still lacking. Molecular simulation provides a means to study and understand these types of processes at the molecular level. Before this potential can be realized, however, appropriate methods must first be developed to enable protein adsorption behavior to be accurately represented in a molecular simulation. This article begins with an overview of some of the fundamentals of protein adsorption. It then introduces the field of molecular simulation and covers a series of topics regarding how molecular simulations are performed, with specific focus on three of the most important issues for the simulation of protein adsorption behavior: force field parameterization, representation of solvent effects, and sampling of the molecular system. A summary is then presented regarding how these methods have been developed and applied to simulate protein–surface interactions over the past two decades. This is followed by a discussion of the key areas for the continued development of molecular simulation methods toward the goal of providing these methods as powerful tools to guide the design of biomaterial surfaces to control protein adsorption behavior for a broad range of applications in biomedical engineering and biotechnology.
Organ-printing techniques offer the potential to produce living 3D tissue constructs to repair or replace damaged or diseased human tissues and organs. Using these techniques, spatial variations along multiple axes with high geometric complexity can be obtained. The level of control offered by these technologies to develop printed tissues will allow tissue engineers to better study factors that modulate tissue formation and function, and provide a valuable tool to study the effect of anatomy on graft performance. In this chapter, we discuss the history behind substrate patterning, and cell and organ printing, and the rationale for developing organ-printing techniques with respect to the limitations of current clinical tissue engineering strategies in effectively repairing damaged tissues. We discuss current two-dimensional and three-dimensional strategies for assembling cells as well as the necessary support materials such as hydrogels, bioinks, and natural and synthetic polymers adopted for organ-printing research. Furthermore, given the current state-of-the-art in organ-printing technologies, we discuss some of their limitations and provide recommendations for future developments in this rapidly growing field.
Affinity-based drug delivery systems provide a simple and gentle method of drug delivery for protein drugs, such as growth factors, because they can be sequestered in their native form. Many growth factors bind to heparin with moderate-to-high affinity, making it ideal for use as a potential binding site. Heparin-binding delivery systems have been developed with both covalent and noncovalent heparin immobilization that provide controlled delivery of growth factors for many applications in regenerative medicine, including angiogenesis and peripheral nerve injury. These heparin immobilization methods can be used with many different types of biomaterial scaffolds, including hydrogels from natural and synthetic materials as well as degradable polyesters, such as poly(lactic- co -glycolic acid), making heparin conjugation a very versatile approach for growth factor delivery. This chapter outlines the rationale for using heparin conjugates, various methods for heparin immobilization, examples of applications of heparin-based delivery systems, and heparin mimetic approaches to drug delivery.
Protein-based 'bottom-up' synthesis of nanoscale functional materials and devices is one of the most promising areas in the newly emerging field of nanotechnology. However, identifying active basic building blocks from biological examples is still a challenge because of their complex and encrypted sequence structure. Genetic engineering of phage viruses provides opportunities for building novel bio-nanomaterials by integrating biology, chemistry, physics, materials science, and electric engineering. By mimicking the evolutionary process in nature, phages can be used as an information-mining tool for identifying functional peptide (or protein) sequences that can specifically recognize desired materials at the molecular level. These recognition elements can be used to guide the design of unprecedented materials such as semiconductor and metallic materials. Moreover, phages are unique in their intrinsic ability to self-replicate within a cellular host and self-assemble into highly ordered two- and three-dimensional nanostructures. By combining these self-replicating and self-assembling functions, virus-based materials can be used to construct nanomaterials and devices with novel structure and function that could be useful in applications including energy, biosensors, electronics, and tissue-regenerating materials. In this chapter, we introduce the unique features of phages and recent accomplishments in the development of virus-based materials for use as tools to fabricate functional nanomaterials, and review the potential future applications of this emerging technology.
The intervertebral disc (IVD) is a complex avascular organ of viscoelastic properties. The current research focus is to regenerate and to partially restore a degenerated IVD by ‘smart’ biomaterials in combination of cell therapy and/or growth factors. For the two tissues of the IVD, that is, the nucleus pulposus (NP) and the annulus fibrosus (AF), biomaterials of different mechanical properties are needed. The ideal biomaterial to restore the water-rich NP and the tensile-force resistant AF has not been identified yet. The lack of blood vessels and the relative scarcity of specially adapted cells of the IVD organ demand novel concepts of tissue-engineered biological approaches to regenerate or replace the IVD. Injectable biodegradable hydrogels with swelling properties are in focus for NP replacement, whereas electrospun biphasic composites and silk, among other biodegradable polymers, are discussed for AF reinforcement.
Shunt infection rates have fallen in recent decades but are still too high, especially when infants under 6 months of age are shunted. The causative bacteria are mainly staphylococci derived from the patient’s skin during operation. Bacteria develop biofilms inside the shunt, and this has important implications for treatment. The protective effect of perioperative antibiotic prophylaxis is weak, leading to increased use of antimicrobial shunt catheters, though greater attention to operating room asepsis and antisepsis is at least as important.
The fields of cardiovascular tissue engineering and regenerative medicine have experienced tremendous expansion and progress over the past 20 years. Strategies have focused on the use of cells, tissues, scaffolds, and numerous combinations of these three components to address both scientific questions and clinical needs. This chapter will focus on the use of biomaterials in the development of cardiac constructs, cell delivery methods, and engineering of artificial vessels and heart valves. While not an exhaustive list of topics within the field of cardiovascular tissue engineering, this list covers major areas of research advancement over the past few decades. Whether cardiac or peripherally focused, progress in these areas of research has the potential to impact tissue and organ function throughout the body. Because the cardiovascular system is dispersed throughout the human body, cardiovascular tissue engineering advancements can be seen as a rate-limiting factor for the development of thick tissues to repair or replace every critical physiological system. In addition, this chapter will also touch upon the prerequisites for continued success in cardiovascular tissue-engineered technology, discussing the future regulatory, clinical, manufacturing, and economic hurdles that scientists will need to overlay.
An increasing number of orthopedic and craniomaxillofacial surgeries is one of the consequences of the current progressive population aging. Availability of a patient's own bone, the gold standard in bone regeneration, is limited, and therefore novel approaches are needed. Tissue engineering, both growth factor and cell based, is a promising alternative; however, its complexity makes the transfer from laboratory to the clinic a long and difficult one. Synthetic biomaterials form an interesting alternative to autogaft because they are available in large quantities off-the-shelf and relatively easy to adapt to various applications. Particularly, calcium phosphate-based synthetic bone graft substitutes such as calcium phosphate (CaP) ceramics are of great interest, as they resemble chemical composition of bone mineral and are therefore not only biocompatible but also bioactive. Biological performance of CaP ceramics in bone regeneration is generally inferior to that of autograft, as their effect on bone cell function and bone tissue formation is less pronounced. Improving the biological performance of bone graft substitutes, while retaining their synthetic character, is a challenge. Use of inorganic compounds, which are present in bone as trace elements and known to be involved in processes related to bone formation and remodeling, as additives to synthetic bone graft substitutes is a potentially interesting approach to improving their biological performance. In this chapter, five inorganic additives are described: three cations, namely, zinc, copper, and strontium, and two anions, namely, fluoride and carbonate. First, their role in bone metabolism and processes related to bone formation and resorption is discussed. Then, a number of methods are described by which these elements can be incorporated into CaP ceramics. Their effect on ceramic properties, as well as their direct or indirect effect on bone formation and resorption processes in vitro and in vivo, is also discussed. Finally, some conclusions and future perspectives are given for further research into synthetic bone graft substitutes.
Conjugated polymers (CPs), or polymers having a conjugated π-electron backbone, have recently attracted much attention from the biosensors research community due to the many promises and advantages that CPs hold for signal amplification in biosensor devices. In this chapter, the use of CPs for biosensor devices has been reviewed and the contents have been broken down into three parts. Part 1 commences with a brief definition of a ‘biosensor’ and why CPs are promising candidates that can facilitate a new generation of biosensors. Subsequently, a brief description covering the synthesis methods of CPs and how CPs can be used for electrochemical and optical biosensors is provided. In Part 2, the use of CPs in electrochemical biosensors is described. Focusing more on the ‘sensing’ component of biosensors, different possibilities to immobilize biological sensing elements (BSEs) onto electrodes of electrochemical CP based biosensors are covered. The choice of immobilization strategy (depending on the type of BSEs utilized) and current research direction of electrochemical CP-based biosensors are discussed. Due to the unique conjugated π-electron backbone system, CPs exhibit different optical properties depending on their adopted state, for example, linear or random coiled. The last part describes different optical sensing approaches, through the use of CPs, for biological analytes that have been demonstrated. Special attention is given to works describing biosensing approaches performed on solid support as these works may be further evolved and employed into biosensor devices.
Magnetic resonance based imaging and diagnostic techniques are essential tools in medicine and will play an important role in the development and implementation of biomaterials for treatment. This chapter discusses important aspects of magnetic resonance as it pertains to imaging and diagnosis of biological markers. Basic MR theory is presented and different markers are briefly discussed to show how the appropriate selection of biological molecules, NMR isotopes, and NMR experimental techniques is important. Finally two case studies that demonstrate how markers can be selected and used for imaging and diagnosis are presented.
