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Many crucial cellular processes in our tissues are governed by complex, spatio-temporally regulated interactions between cells and their extracellular matrix (ECM). These interactions can be studied using well-established 3D in vitro model systems such as collagen gels or Matrigel generated from native ECM macromolecular components. Recent advances in the molecular design of 'smart' synthetic biomaterials have generated artificial ECM (aECM) that mimic some of the key structural and biochemical characteristics of their naturally derived counterparts and, thanks to their synthetic origin, promise to overcome some complexities of the latter. Here I will discuss emerging approaches in aECM design, hopefully inspiring cell biologists to apply these systems to address their specific biological question.

The structural features of tissue engineering scaffolds affect cell response and must be engineered to support cell adhesion, proliferation and differentiation. The scaffold acts as an interim synthetic extracellular matrix (ECM) that cells interact with prior to forming a new tissue. In this review, bone tissue engineering is used as the primary example for the sake of brevity. We focus on nanofibrous scaffolds and the incorporation of other components including other nanofeatures into the scaffold structure. Since the ECM is comprised in large part of collagen fibers, between 50 and 500 nm in diameter, well-designed nanofibrous scaffolds mimic this structure. Our group has developed a novel thermally induced phase separation (TIPS) process in which a solution of biodegradable polymer is cast into a porous scaffold, resulting in a nanofibrous pore-wall structure. These nanoscale fibers have a diameter (50-500 nm) comparable to those collagen fibers found in the ECM. This process can then be combined with a porogen leaching technique, also developed by our group, to engineer an interconnected pore structure that promotes cell migration and tissue ingrowth in three dimensions. To improve upon efforts to incorporate a ceramic component into polymer scaffolds by mixing, our group has also developed a technique where apatite crystals are grown onto biodegradable polymer scaffolds by soaking them in simulated body fluid (SBF). By changing the polymer used, the concentration of ions in the SBF and by varying the treatment time, the size and distribution of these crystals are varied. Work is currently being done to improve the distribution of these crystals throughout three-dimensional scaffolds and to create nanoscale apatite deposits that better mimic those found in the ECM. In both nanofibrous and composite scaffolds, cell adhesion, proliferation and differentiation improved when compared to control scaffolds. Additionally, composite scaffolds showed a decrease in incidence of apoptosis when compared to polymer control in bone tissue engineering. Nanoparticles have been integrated into the nanostructured scaffolds to deliver biologically active molecules such as growth and differentiation factors to regulate cell behavior for optimal tissue regeneration., ((c) 2009 John Wiley & Sons, Inc.)

Angiogenesis precedes recovery following spinal cord injury and its extent correlates with neural regeneration, suggesting that angiogenesis may play a role in repair. An important precondition for studying the role of angiogenesis is the ability to induce it in a controlled manner. Previously, we showed that a coculture of endothelial cells (ECs) and neural progenitor cells (NPCs) promoted the formation of stable tubes in vitro and stable, functional vascular networks in vivo in a subcutaneous model. We sought to test whether a similar coculture would lead to the formation of stable functional vessels in the spinal cord following injury. We created microvascular networks in a biodegradable two-component implant system and tested the ability of the coculture or controls (lesion control, implant alone, implant + ECs or implant + NPCs) to promote angiogenesis in a rat hemisection model of spinal cord injury. The coculture implant led to a fourfold increase in functional vessels compared with the lesion control, implant alone or implant + NPCs groups and a twofold increase in functional vessels over the implant + ECs group. Furthermore, half of the vessels in the coculture implant exhibited positive staining for the endothelial barrier antigen, a marker for the formation of the blood-spinal cord barrier. No other groups have shown positive staining for the blood-spinal cord barrier in the injury epicenter. This work provides a novel method to induce angiogenesis following spinal cord injury and a foundation for studying its role in repair.

Articular cartilage repair and regeneration continue to be largely intractable because of the poor regenerative properties of this tissue. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased articular cartilage functionality, has evoked intense interest and holds great potential for improving articular cartilage therapy. This review provides an overall description of the current state of and progress in articular cartilage repair and regeneration. Traditional therapies and related problems are introduced. More importantly, a variety of promising cell sources, biocompatible tissue engineered scaffolds, scaffoldless techniques, growth factors, and mechanical stimuli used in current articular cartilage tissue engineering are reviewed. Finally, the technical and regulatory challenges of articular cartilage tissue engineering and possible future directions are also discussed.

Disc degeneration is a common disorder. Although the back pain that can develop in association with this is rarely life-threatening, the annual cost in terms of morbidity, lost productivity, medical expenses and workers' compensation benefits is significant. Surgical intervention as practised currently is directed towards removing the damaged or altered tissue. Development of new treatment modalities is critical as there is a growing consensus that the strategies used currently for symptomatic degenerative disc disease may not be effective. Accordingly, there is a need to develop an entirely new way to treat this disorder; regenerative medicine and tissue engineering approaches appear particularly promising in this regard. This paper reviews some of the challenges that currently are limiting the clinical application of this approach to the treatment of disc degeneration.

Scaffolds represent important components for tissue engineering. However, researchers often encounter an enormous variety of choices when selecting scaffolds for tissue engineering. This paper aims to review the functions of scaffolds and the major scaffolding approaches as important guidelines for selecting scaffolds and discuss the tissue-specific considerations for scaffolding, using intervertebral disc as an example.

As one of the key factors for tissue engineering, scaffolds affect the spread and proliferation of seeded cells and the formation of new tissue. Although conventional methods can produce porous scaffolds with different porosities, they are lack controls the porous structures of the scaffolds. In recent years, rapid prototyping (RP) techniques have been developed and have successfully applied to fabricate TE scaffolds. RP techniques can provide accurate control over internal pore architectures and complex-shapes. As a result of these techniques, ideal tissue-engineered constructs could be prepared. This paper reviewed the advantages, potential and future directions of RP techniques in the design and fabrication of TE scaffolds.

Tissue engineering is expected to help us outlive the failure of our organs by enabling the creation of tissue substitutes capable of fully restoring the original tissue function. Degenerative joint disease, which affects one-fifth of the US population and is the country's leading cause of disability, drives current research of actively growing, functional tissue grafts for joint repair. Toward this goal, living cells are used in conjunction with biomaterial scaffolds (serving as instructive templates for tissue development) and bioreactors (providing environmental control and molecular and physical regulatory signals). In this review, we discuss the requirements for engineering customized, anatomically-shaped, stratified grafts for joint repair and the challenges of designing these grafts to provide immediate functionality (load bearing, structural support) and long-term regeneration (maturation, integration, remodeling).

Tendon traumas or diseases are prevalent and debilitating lesions that affect the quality of life among populations worldwide. As a novel solution, tendon tissue engineering aims to address these lesions by integrating engineered, living substitutes with their native counterparts in vivo, thereby restoring the defective functions in situ. For such a purpose, competent scaffolding materials are essential. To date, three major categories of scaffolding materials have been employed: polyesters, polysaccharides, and collagen derivatives. Furthermore, with these materials as a base, a variety of specialized methodologies have been developed or adopted to enhance neo-tendogenesis. These strategies include cellular hybridization, interfacing improvement, and physical stimulation.

The present study compares fibroblasts extracted from intact and ruptured human anterior cruciate ligaments (ACL) for creation of a tissue engineered ACL-construct, made of porcine small intestinal submucosal extracellular matrix (SIS-ECM) seeded with these ACL cells. The comparison is based on histological, immunohistochemical and RT-PCR analyses. Differences were observed between cells in a ruptured ACL (rACL) and cells in an intact ACL (iACL), particularly with regard to the expression of integrin subunits and smooth muscle actin (SMA). Despite these differences in the cell source, both cell populations behaved similarly when seeded on an SIS-ECM scaffold, with similar cell morphology, connective tissue organization and composition, SMA and integrin expression. This study shows the usefulness of naturally occurring scaffolds such as SIS-ECM for the study of cell behaviour in vitro, and illustrates the possibility to use autologous cells extracted from ruptured ACL biopsies as a source for tissue engineered ACL constructs.

The influence of the properties and surface micropatterning of chitosan-collagen-gelatin (CCG) blended membranes on C3A cell's activities has been investigated. It is aimed to guide the cell growth and improve the growth rate in vitro for the application in tissue engineering. Masters with micropatterns are prepared on stainless steel plates by photolithography. The CCG membranes with surface micropatterns are then fabricated by soft lithography and dry-wet phase inversion techniques. The morphology and metabolic activity of cultured C3A cells on the membranes are recorded. When the C3A cells are seeded on the membranes with micropattern spacing of 200 microm width and 80 microm depth, they adhere and aggregate in the groove of the membranes in a few minutes. The aggregated cells migrate up to the surface of the ridge later. This phenomenon, however, is not found on membranes with a micropattern spacing of 500 microm width. In addition, it is demonstrated that the cells on the CCG membranes with micropatterns have higher metabolism and growth rates than those on the flat CCG membranes and on T-flask discs. Micropatterning on the membrane surface can affect the distribution of cells and the communication among cells, and results in a difference in cell adhesion, morphology, mobility, and growth activity.