Showing papers in "Tissue Engineering Part B-reviews in 2011"

Indentation versus tensile measurements of Young's modulus for soft biological tissues.

Abstract: In this review, we compare the reported values of Young's modulus (YM) obtained from indentation and tensile deformations of soft biological tissues. When the method of deformation is ignored, YM values for any given tissue typically span several orders of magnitude. If the method of deformation is considered, then a consistent and less ambiguous result emerges. On average, YM values for soft tissues are consistently lower when obtained by indentation deformations. We discuss the implications and potential impact of this finding.

Hydrogels for the Repair of Articular Cartilage Defects

Abstract: The repair of articular cartilage defects remains a significant challenge in orthopedic medicine. Hydrogels, three-dimensional polymer networks swollen in water, offer a unique opportunity to generate a functional cartilage substitute. Hydrogels can exhibit similar mechanical, swelling, and lubricating behavior to articular cartilage, and promote the chondrogenic phenotype by encapsulated cells. Hydrogels have been prepared from naturally derived and synthetic polymers, as cell-free implants and as tissue engineering scaffolds, and with controlled degradation profiles and release of stimulatory growth factors. Using hydrogels, cartilage tissue has been engineered in vitro that has similar mechanical properties to native cartilage. This review summarizes the advancements that have been made in determining the potential of hydrogels to replace damaged cartilage or support new tissue formation as a function of specific design parameters, such as the type of polymer, degradation profile, mechanical properties and loading regimen, source of cells, cell-seeding density, controlled release of growth factors, and strategies to cause integration with surrounding tissue. Some key challenges for clinical translation remain, including limited information on the mechanical properties of hydrogel implants or engineered tissue that are necessary to restore joint function, and the lack of emphasis on the ability of an implant to integrate in a stable way with the surrounding tissue. Future studies should address the factors that affect these issues, while using clinically relevant cell sources and rigorous models of repair.

Scaffolds based bone tissue engineering: the role of chitosan.

Abstract: As life expectancy increases, malfunction or loss of tissue caused by injury or disease leads to reduced quality of life in many patients at significant socioeconomic cost. Even though major progress has been made in the field of bone tissue engineering, present therapies, such as bone grafts, still have limitations. Current research on biodegradable polymers is emerging, combining these structures with osteogenic cells, as an alternative to autologous bone grafts. Different types of biodegradable materials have been proposed for the preparation of three-dimensional porous scaffolds for bone tissue engineering. Among them, natural polymers are one of the most attractive options, mainly due to their similarities with extracellular matrix, chemical versatility, good biological performance, and inherent cellular interactions. In this review, special attention is given to chitosan as a biomaterial for bone tissue engineering applications. An extensive literature survey was performed on the preparation of chitosan scaffolds and their in vitro biological performance as well as their potential to facilitate in vivo bone regeneration. The present review also aims to offer the reader a general overview of all components needed to engineer new bone tissue. It gives a brief background on bone biology, followed by an explanation of all components in bone tissue engineering, as well as describing different tissue engineering strategies. Moreover, also discussed are the typical models used to evaluate in vitro functionality of a tissue-engineered construct and in vivo models to assess the potential to regenerate bone tissue are discussed.

Polymeric nanofibers in tissue engineering.

Abstract: Polymeric nanofibers can be produced using methods such as electrospinning, phase separation, and self-assembly, and the fiber composition, diameter, alignment, degradation, and mechanical properties can be tailored to the intended application. Nanofibers possess unique advantages for tissue engineering. The small diameter closely matches that of extracellular matrix fibers, and the relatively large surface area is beneficial for cell attachment and bioactive factor loading. This review will update the reader on the aspects of nanofiber fabrication and characterization important to tissue engineering, including control of porous structure, cell infiltration, and fiber degradation. Bioactive factor loading will be discussed with specific relevance to tissue engineering. Finally, applications of polymeric nanofibers in the fields of bone, cartilage, ligament and tendon, cardiovascular, and neural tissue engineering will be reviewed.

Increasing the Pore Size of Electrospun Scaffolds

Abstract: Electrospinning has gained much attention in the past decade as an effective means of generating nano- to micro-scale polymer fibers that resemble native extracellular matrix. High porosity, pore i...

Bone Tissue Engineering and Regeneration: From Discovery to the Clinic—An Overview

Abstract: A National Institutes of Health sponsored workshop “Bone Tissue Engineering and Regeneration: From Discovery to the Clinic” gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics.

Mechanical Properties of Natural Cartilage and Tissue-Engineered Constructs

Abstract: There has been much research over the past two decades with the aim of engineering cartilage constructs for repairing or restoring damaged cartilage. To engineer healthy neocartilage, the constructs must have mechanical properties matching those of native cartilage as well as appropriate for the loading conditions of the joint. This article discusses the mechanical behavior of native cartilage and surveys different types of tensile, compressive, and shear tests with their limitations. It also comprehensively reviews recent work and achievements in developing the mathematical models representing the mechanical properties of both native and engineered cartilage. Different methods for enhancing the mechanical properties of engineered cartilage are also discussed, including scaffold design, mechanical stimulation, and chemical stimulation. This article concludes with recommendations for future research aimed at achieving engineered cartilage with mechanical properties matching those found in native cartilage.

Bioreactor Systems for Bone Tissue Engineering

Abstract: Bone graft material is often required for the treatment of osseous defects. However, due to limitations and risks associated with autologous as well as allogenic bone grafting procedures, alternative strategies are needed. In this context, ex vivo tissue engineering (TE) strategies for de novo generation of bone tissue include the combined use of autologous bone-forming cells and three-dimensional (3D) porous scaffold materials serving as structural support for the cells. Three-dimensional cultivation of osteoprogenitor cells presents several challenges, for example, insufficient nutrient and oxygen transport to and removal of waste products from the cells at the interior of the scaffold. By providing physical stimulation of tissue-engineered constructs and resolving mass transport limitations bioreactor systems denote key components for bone TE strategies. A variety of dynamic 3D bioreactor concepts mimicking the native microenvironment in bone tissue, for example, spinner flasks, rotating wall vessel constructs, perfusion bioreactors, and systems based on mechanical or electromagnetic stimulation of cell/scaffold composites, have been developed. These techniques differ considerably with respect to ease of use, cost-effectiveness, and degree of additional osteogenic stimuli, as well as monitoring and manipulation options. This review provides an overview of the concepts, advantages, challenges, and potential future applications associated with current bioreactor systems for bone TE.

Harnessing and modulating inflammation in strategies for bone regeneration.

Abstract: Inflammation is an immediate response that plays a critical role in healing after fracture or injury to bone. However, in certain clinical contexts, such as in inflammatory diseases or in response to the implantation of a biomedical device, the inflammatory response may become chronic and result in destructive catabolic effects on the bone tissue. Since our previous review 3 years ago, which identified inflammatory signals critical for bone regeneration and described the inhibitory effects of anti-inflammatory agents on bone healing, a multitude of studies have been published exploring various aspects of this emerging field. In this review, we distinguish between regenerative and damaging inflammatory processes in bone, update our discussion of the effects of anti-inflammatory agents on bone healing, summarize recent in vitro and in vivo studies demonstrating how inflammation can be modulated to stimulate bone regeneration, and identify key future directions in the field.

Scaffold translation: barriers between concept and clinic.

Abstract: Translation of scaffold-based bone tissue engineering (BTE) therapies to clinical use remains, bluntly, a failure. This dearth of translated tissue engineering therapies (including scaffolds) remains despite 25 years of research, research funding totaling hundreds of millions of dollars, over 12,000 papers on BTE and over 2000 papers on BTE scaffolds alone in the past 10 years (PubMed search). Enabling scaffold translation requires first an understanding of the challenges, and second, addressing the complete range of these challenges. There are the obvious technical challenges of designing, manufacturing, and functionalizing scaffolds to fill the Form, Fixation, Function, and Formation needs of bone defect repair. However, these technical solutions should be targeted to specific clinical indications (e.g., mandibular defects, spine fusion, long bone defects, etc.). Further, technical solutions should also address business challenges, including the need to obtain regulatory approval, meet specific market needs, and obtain private investment to develop products, again for specific clinical indications. Finally, these business and technical challenges present a much different model than the typical research paradigm, presenting the field with philosophical challenges in terms of publishing and funding priorities that should be addressed as well. In this article, we review in detail the technical, business, and philosophical barriers of translating scaffolds from Concept to Clinic. We argue that envisioning and engineering scaffolds as modular systems with a sliding scale of complexity offers the best path to addressing these translational challenges.

What we should know before using tissue engineering techniques to repair injured tendons: a developmental biology perspective.

Abstract: Tendons connect muscles to bones, and serve as the transmitters of force that allow all the movements of the body. Tenocytes are the basic cellular units of tendons, and produce the collagens that form the hierarchical fiber system of the tendon. Tendon injuries are common, and difficult to repair, particularly in the case of the insertion of tendon into bone. Successful attempts at cell-based repair therapies will require an understanding of the normal development of tendon tissues, including their differentiated regions such as the fibrous mid-section and fibrocartilaginous insertion site. Many genes are known to be involved in the formation of tendon. However, their functional roles in tendon development have not been fully characterized. Tissue engineers have attempted to generate functional tendon tissue in vitro. However, a lack of knowledge of normal tendon development has hampered these efforts. Here we review studies focusing on the developmental mechanisms of tendon development, and discuss the ...

The Multiparametric Effects of Hydrodynamic Environments on Stem Cell Culture

Abstract: Stem cells possess the unique capacity to differentiate into many clinically relevant somatic cell types, making them a promising cell source for tissue engineering applications and regenerative medicine therapies. However, in order for the therapeutic promise of stem cells to be fully realized, scalable approaches to efficiently direct differentiation must be developed. Traditionally, suspension culture systems are employed for the scale-up manufacturing of biologics via bioprocessing systems that heavily rely upon various types of bioreactors. However, in contrast to conventional bench-scale static cultures, large-scale suspension cultures impart complex hydrodynamic forces on cells and aggregates due to fluid mixing conditions. Stem cells are exquisitely sensitive to environmental perturbations, thus motivating the need for a more systematic understanding of the effects of hydrodynamic environments on stem cell expansion and differentiation. This article discusses the interdependent relationships betwe...

Microcarriers and their potential in tissue regeneration.

Abstract: Microcarriers are a versatile tool with applications across a wide range of disciplines within tissue engineering. Large numbers of cells of appropriate phenotypes are required in engineering the many different tissues of the body, and microcarriers facilitate not only the expansion of many cell types but also the investigation of cell behavior in vitro. Microcarriers can also be used to directly deliver cells in vivo to repair and regenerate tissues. This review summarizes and discusses the use of microcarriers in diverse applications of tissue repair, including bone, cartilage, skin, vascular, central nervous system, adipose tissue, and liver repair. It also considers how microcarriers can be used to bulk-culture and deliver stem cells for tissue regeneration. Microcarriers thus have multidisciplinary use and advances in their use are of benefit to the entire tissue engineering field.

Biomaterial selection for tooth regeneration.

Abstract: Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or synthetic polymers, three-dimensional scaffold fabrication, stem cell transplantation, and stem cell homing. A tooth is a complex biological organ. Tooth loss represents the most common organ failure. Tooth regeneration encompasses not only regrowth of an entire tooth as an organ, but also biological restoration of individual components of the tooth including enamel, dentin, cementum, or dental pulp. Regeneration of tooth root represents perhaps more near-term opportunities than the regeneration of the whole tooth. In the adult, a tooth owes its biological vitality, arguably more, to the root than the crown. Biomaterials are indispensible for the regeneration of tooth root, tooth crown, dental pulp, or an entire tooth.

Polyelectrolyte multilayers in tissue engineering.

Abstract: The layer-by-layer assembly of sequentially adsorbed, alternating polyelectrolytes has become increasingly important over the past two decades. The ease and versatility in assembling polyelectrolyte multilayers (PEMs) has resulted in numerous wide ranging applications of these materials. More recently, PEMs are being used in biological applications ranging from biomaterials, tissue engineering, regenerative medicine, and drug delivery. The ability to manipulate the chemical, physical, surface, and topographical properties of these multilayer architectures by simply changing the pH, ionic strength, thickness, and postassembly modifications render them highly suitable to probe the effects of external stimuli on cellular responsiveness. In the field of regenerative medicine, the ability to sequester growth factors and to tether peptides to PEMs has been exploited to direct the lineage of progenitor cells and to subsequently maintain a desired phenotype. Additional novel applications include the use of PEMs in the assembly of three-dimensional layered architectures and as coatings for individual cells to deliver tunable payloads of drugs or bioactive molecules. This review focuses on literature related to the modulation of chemical and physical properties of PEMs for tissue engineering applications and recent research efforts in maintaining and directing cellular phenotype in stem cell differentiation.

Elastin as a Nonthrombogenic Biomaterial

Abstract: Surface-induced thrombosis is a significant issue for artificial blood-contacting materials used in the treatment of cardiovascular diseases. The development of biomaterials and tissue-engineered constructs that mimic the vasculature represents a way to overcome this problem. Elastin is an extracellular matrix macromolecule that imparts arterial elasticity where it comprises up to 50% of the nonhydrated mass of the vessel. In addition to its critical role in maintaining vessel integrity and elastic properties under pulsatile flow, elastin plays an important role in signaling and regulating luminal endothelial cells and smooth muscle cells in the arterial wall. Despite its well-established significance in the vasculature and its growing use as a biomaterial in tissue engineering, the hemocompatibility of elastin is often overlooked. Past studies pointing to the potential of arterial elastin and decellularized elastin as nonthrombogenic materials have begun to be realized, with elastin scaffolds and coatings displaying increased hemocomptibility. This review explores the mechanisms of elastin's nonthrombogenicity and highlights the current problems limiting its wider application as a biomaterial. We discuss the benefits of constructing biomaterials encompassing the relevant mechanical and biological features of elastin to provide enhanced hemocompatibility to biomaterials.

Cell Sources for Bone Regeneration: The Good, the Bad, and the Ugly (But Promising)

Abstract: Based on the extensive investigation of various ways to regenerate bone, bone marrow stromal cells, in conjunction with ceramic scaffolds, show great promise for application in human patients, and are already in use in a limited number of clinical trials. In preparing for clinical trials, scale-up current good manufacturing processes (cGMP) must incorporate the use of appropriate assays to ensure that the resulting cell product has maintained its biological activity. Future developments are needed to identify better scaffolds, and better ways to deliver cells with either injectable carriers, or by developing techniques to aide in their escape from the circulation and their incorporation into the pre-existing tissue. Lastly, development of methods that faithfully direct pluripotent stem cell differentiation into populations of osteogenic precursors (and ideally, containing skeletal stem cells) represents a new challenge in the field of bone regeneration, but also offer new opportunities to not only to study the biology of bone formation, but also to develop a robust cell source for bone regeneration.

Severe Burn Injuries and the Role of Elastin in the Design of Dermal Substitutes

Abstract: Severe burn injuries are a major health problem as they can compromise whole body function and result in extensive emotional trauma exacerbated by prolonged hospital stay. Burn injury treatment has improved dramatically to increase the probability of survival, but burn survivors still suffer from excessive scarring and skin contractures, which substantially compromise their health and quality of life. Elastin is historically underrepresented in commercial dermal substitutes, yet deserves consideration because of its fundamental role in skin structure and function. Dermal elastic network is a strong determinant of skin resilience, texture, and quality but is not sufficiently regenerated following burn injury. In addition to its structural and mechanical roles, elastin has inherent cell signaling properties that promote a diverse range of cellular responses including chemotaxis, cell attachment, proliferation, and differentiation. Scaffold elasticity and regeneration of the elastic fiber system is now recognized as integral to the development of functional dermal substitutes. Dermal substitutes are intended to replace damaged dermal tissue in severe burn injuries. Elastin-based dermal substitutes have the potential to decrease wound contraction, improve scar appearance and functionality, and contribute to wound healing outcomes through a combination of elastin's mechanical and cell signaling properties.

Cell Sources for Bone Tissue Engineering: Insights from Basic Science

Abstract: One of the goals of bone tissue engineering is to design delivery methods for skeletal stem/progenitor cells to repair or replace bone. Although the materials used to retain cells play a central role in the quality of the constructs, the source of cells is key for bone regeneration. Bone marrow is the most common cell source, but other tissues are now being explored, such as the periosteum, fat, muscle, cord blood, and embryonic or induced pluripotent stem cells. The therapeutic effect of exogenous stem/progenitor cells is accepted, yet their contribution to bone repair is not well defined. The in vitro osteo- and/or chondrogenic potential of these skeletal progenitors do not necessarily predict their differentiation potential in vivo and their function may be affected by their ability to home correctly to bone. This review provides an overview of animal models used to test the efficacy of cell-based approaches. We examine the mechanisms of endogenous cell recruitment during bone repair and compare the role of local versus systemic cell recruitment. We discuss how the normal repair process can help define efficacious cell sources for bone tissue engineering and improve their methods of delivery.

Cell-based vascularization strategies for skin tissue engineering.

Abstract: Providing a blood-vascular network to promote survival and integration of cells in thick dermal substitutes for application in full-thickness wounds is essential for the successful outcome of skin tissue engineering. Nevertheless, promoting vascularization also represents a critical bottleneck in today's skin tissue engineering practice. Several cell types have been considered and tested, mostly in preclinical studies, to increase vascularization. When the clinical situation allows delayed reconstruction of the defect, an autologous approach is preferable, whereas in acute cases allogeneic therapy is needed. In both cases, the cells should be harvested with minimal donor-site morbidity and should be available in large amounts and safe in terms of tumor formation and transmission of animal diseases. Here, we outline the different mechanisms of cell-based vascularization and subsequently elaborate in more detail on the candidate cell types and their pros and cons in terms of clinical application and regulation of the wound healing process.

Bioengineered scaffolds for spinal cord repair.

Abstract: Spinal cord injury can lead to devastating and permanent loss of neurological function, affecting all levels below the site of trauma. Unfortunately, the injured adult mammalian spinal cord displays little regenerative capacity and little functional recovery in large part due to a tissue environment that is nonpermissive for regenerative axon growth. Artificial tissue repair scaffolds may provide a physical guide to allow regenerative axon growth that bridges the lesion cavity and restores functional neural connectivity. By integrating different strategies, including the use of various biomaterials and microstructures as well as incorporation of bioactive molecules and living cells, combined or synergistic effects for spinal cord repair through regenerative axon growth may be achieved. This article briefly reviews the development of bioengineered scaffolds for spinal cord repair, focusing on spinal cord injury and the subsequent cellular response, scaffold materials, fabrication techniques, and current th...

Matrix components and scaffolds for sustained islet function

Abstract: The clinical treatment of diabetes by islet transplantation is limited by low islet survival rates. A fundamental reason for this inefficiency is likely due to the removal of islets from their native environment. The isolation process not only disrupts interactions between blood vessels and endocrine cells, but also dramatically changes islet cell interaction with the extracellular matrix (ECM). Biomolecular cues from the ECM are important for islet survival, proliferation, and function; however, very little is known about the composition of islet ECM and the role each component plays. Without a thorough understanding of islet ECM, current endeavors to prolong islet survival via scaffold engineering lack a systematic basis. The following article reviews current knowledge of islet ECM and attempts to explain the roles they play in islet function. In addition, the effects of in vitro simulations of the native islet scaffold will be evaluated. Greater understanding in these areas will provide a preliminary platform from which a sustainable bioartificial pancreas may be developed.

Evaluation of Angiogenesis and Osteogenesis

Abstract: Bone regeneration has long been a major focus for tissue engineers and the importance of vascularization to the bone regeneration process has been well documented. Over the past decade, technological advances in the areas of stem cell biology, scaffold fabrication, and protein engineering have significantly enhanced our understanding of the interplay between vascularization and bone growth. This review, therefore, describes the commonly used models for investigating the complex interactions between osteoblastic cells and endothelial cells, evaluates the different tools utilized to investigate the relationship between vascularization and bone growth in vivo, and finally, summarizes possible areas of research related to therapeutic development.

Electric field-guided neuron migration: a novel approach in neurogenesis.

Abstract: Effective directional neuron migration is crucial in development of the central nervous system and for neurogenesis. Endogenous electrical signals are present in many developing systems and crucial cellular behaviors such as neuronal cell division, cell migration, and cell differentiation are all under the influence of such endogenous electrical cues. Preclinical in vivo studies have used electric fields (EFs) to attempt to enhance regrowth of damaged spinal cord axons with some success. Recent evidence shows that small EFs not only guide axonal growth, but also direct the earlier events of neuronal migration and neuronal cell division. This raises the possibility that applied or endogenous EFs, perhaps in combination, may direct transplanted neural stem cells, or regenerating neurons, to the desired site after brain injury or neuron degeneration. The high complexity of both structure and function of the nervous system, however, poses significant challenges to techniques for applying EFs to promote neurog...

Next generation of electrosprayed fibers for tissue regeneration.

Abstract: Electrospinning is a widely established polymer-processing technology that allows generation of fibers (in nanometer to micrometer size) that can be collected to form nonwoven structures. By choosing suitable process parameters and appropriate solvent systems, fiber size can be controlled. Since the technology allows the possibility of tailoring the mechanical properties and biological properties, there has been a significant effort to adapt the technology in tissue regeneration and drug delivery. This review focuses on recent developments in adapting this technology for tissue regeneration applications. In particular, different configurations of nozzles and collector plates are summarized from the view of cell seeding and distribution. Further developments in obtaining thick layers of tissues and thin layered membranes are discussed. Recent advances in porous structure spatial architecture parameters such as pore size, fiber size, fiber stiffness, and matrix turnover are summarized. In addition, possibil...

Adipose-Derived Stem Cells in Functional Bone Tissue Engineering: Lessons from Bone Mechanobiology

Abstract: This review aims to highlight the current and significant work in the use of adipose-derived stem cells (ASC) in functional bone tissue engineering framed through the bone mechanobiology perspective. Over a century of work on the principles of bone mechanosensitivity is now being applied to our understanding of bone development. We are just beginning to harness that potential using stem cells in bone tissue engineering. ASC are the primary focus of this review due to their abundance and relative ease of accessibility for autologous procedures. This article outlines the current knowledge base in bone mechanobiology to investigate how the knowledge from this area has been applied to the various stem cell-based approaches to engineering bone tissue constructs. Specific emphasis is placed on the use of human ASC for this application.

Nanomaterials and Hydrogel Scaffolds for Articular Cartilage Regeneration

Abstract: Osteoarthritis (OA) is a major clinical and scientific challenge. The degradation of articular cartilage in the joints is a common manifestation of painful arthritis. The regeneration of articular cartilage in OA is an unmet clinical need. The assembly of articular cartilage by tissue engineering toward complete regeneration is the goal of most scientists and surgeons. The key ingredients for regeneration are signals, stem cells, and scaffolds. This brief review focuses on the scaffold, with special emphasis on hydrogels and nanomaterials for the assembly of tissue-engineered cartilage, and ultimately leading to the total regeneration of articular cartilage in the joints.

Skeletal Tissue Regeneration: Current Approaches, Challenges, and Novel Reconstructive Strategies for an Aging Population

Abstract: Loss of skeletal tissue as a consequence of trauma, injury, or disease is a significant cause of morbidity with often wide-ranging socioeconomic impacts. Current approaches to replace or restore significant quantities of lost bone come with substantial limitations and inherent disadvantages that may in themselves cause further disability. In addition, the spontaneous repair capacity of articular cartilage is limited; thus, investigation into new cartilage replacement and regeneration techniques are warranted. Along with the challenges of an increasingly aging demographic, changing clinical scenarios and rising functional expectations provide the imperative for new, more reliable skeletal regeneration strategies. The science of tissue engineering has expanded dramatically in recent years, notably in orthopedic applications, and it is clear that new approaches for de novo skeletal tissue formation offer exciting opportunities to improve the quality of life for many, particularly in the face of increasing patient expectations. However, significant scientific, financial, industrial, and regulatory challenges should be overcome before the successful development of an emergent tissue engineering strategy can be realized. We outline current practice for replacement of lost skeletal tissue and the innovative approaches in tissue regeneration that have so far been translated to clinical use, along with a discussion of the significant hurdles that are presented in the process of translating research strategies to the clinic.

Carbon nanotubes in animal models: a systematic review on toxic potential.

Abstract: Amongst the engineered nanomaterials, especially carbon nanotubes (CNTs) have received considerable attention for application in tissue engineering scaffolds. CNTs are considered promising on behalf of their physicochemical properties, yet such nanomaterials also have been associated with potentially hazardous effects on human health. To gain insight into the toxicity aspects of CNTs in vivo, the present study presents a systematic review of literature. After screening of literature through defined inclusion and exclusion criteria, and subsequent data extraction, it can be concluded that pulmonary administered CNTs have the capacity to induce toxicity in the lung area. However, conclusions for other organs, or on systemic toxicity, are yet premature. In addition, the carcinogenic potential of CNTs is also still ambiguous, because contradictive results are presented. Intrinsic factors, such as material characteristics, and associated distribution and agglomeration patterns influence the toxic potential of CNTs. Similarly, environmental factors such as the exposure route, preexisting allergies, pathological infections, or air pollutant exposure are significant. Despite the many reports published currently, more studies will be required to gain full understanding of the toxic potential of CNTs and especially the underlying mechanisms. For this end, development of standardized protocols and reliable nanodetection techniques will form prerequisites.

Barriers to the Clinical Translation of Orthopedic Tissue Engineering

Abstract: Tissue engineering and regenerative medicine have been the subject of increasingly intensive research for over 20 years, and there is concern in some quarters over the lack of clinically useful products despite the large sums of money invested. This review provides one perspective on orthopedic applications from a biologist working in academia. It is suggested that the delay in clinical application is not atypical of new, biologically based technologies. Some barriers to progress are acknowledged and discussed, but it is also noted that preclinical studies have identified several promising types of cells, scaffolds, and morphogenetic signals, which, although not optimal, are worth advancing toward human trials to establish a bridgehead in the clinic. Although this transitional technology will be replaced by more sophisticated, subsequent systems, it will perform valuable pioneering functions and facilitate the clinical development of the field. Some strategies for achieving this are suggested.