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Tendons and ligaments have a poor innate healing capacity, yet account for 50% of musculoskeletal injuries in the United States. Full structure and function restoration postinjury remains an unmet clinical need. This study aimed to assess the application of novel three dimensional (3D) printed scaffolds and induced pluripotent stem cell‐derived mesenchymal stem cells (iMSCs) overexpressing the transcription factor Scleraxis (SCX, iMSCSCX+) as a new strategy for tendon defect repair. The polycaprolactone (PCL) scaffolds were fabricated by extrusion through a patterned nozzle or conventional round nozzle. Scaffolds were seeded with iMSCSCX+ and outcomes were assessed in vitro via gene expression analysis and immunofluorescence. In vivo, rat Achilles tendon defects were repaired with iMSCSCX+‐seeded microgrooved scaffolds, microgrooved scaffolds only, or suture only and assessed via gait, gene expression, biomechanical testing, histology, and immunofluorescence. iMSCSCX+‐seeded on microgrooved scaffolds showed upregulation of tendon markers and increased organization and linearity of cells compared to non‐patterned scaffolds in vitro. In vivo gait analysis showed improvement in the Scaffold + iMSCSCX+‐treated group compared to the controls. Tensile testing of the tendons demonstrated improved biomechanical properties of the Scaffold + iMSCSCX+ group compared with the controls. Histology and immunofluorescence demonstrated more regular tissue formation in the Scaffold + iMSCSCX+ group. This study demonstrates the potential of 3D‐printed scaffolds with cell‐instructive surface topography seeded with iMSCSCX+ as an approach to tendon defect repair. Further studies of cell‐scaffold constructs can potentially revolutionize tendon reconstruction by advancing the application of 3D printing‐based technologies toward patient‐specific therapies that improve healing and functional outcomes at both the cellular and tissue level. [ABSTRACT FROM AUTHOR]

Background: Tremendous progress has been made in the field of cartilage repair and regeneration, particularly with tissue-engineering approaches. This study aims to estimate the global status and current trends in the field of cartilage tissue engineering. Methods: Publications from 2011 to 2020 on tissue engineering for cartilage repair and regeneration were retrieved from Web of Science Core Collection database. The source data were statistically evaluated based on the bibliometrics. In terms of visualized analysis, some bibliometric indicators such as bibliographic coupling, co-citation, co-authorship and co-occurrence analysis were performed by VOSviewer software, to investigate the research trends in tissue engineering for cartilage repair and regeneration. Results: In total, 3715 papers were included. Since 2011, the amount of issued papers and relative research interest (RRI) have grown by leaps and bounds globally. The United States was the biggest contributor to the research in this field, due to the greatest citation frequency, the highest H index and the strongest total link strength. Romania had the highest average citation for each. The journal Tissue Engineering Part A published most articles in this field. For institutions, the largest contributors were Shanghai Jiaotong University, University of California System and Sichuan University. Studies could all be grouped into four main clusters: study of biomaterial scaffolds, study of seeding cells and growth factors, experimental animal model and clinical study, and mechanism research. Conclusion: Great efforts should be put into the study of biomaterial scaffolds, seeding cells and growth factors, considered to be the next hot topics in cartilage tissue engineering. This findings provide collaborative insights and research orientation for academic researchers, surgeons and healthcare practitioners to a certain extent. [ABSTRACT FROM AUTHOR]

Significant bone loss due to disease or severe injury can result in the need for a bone graft, with over 500,000 procedures occurring each year in the United States. However, the current standards for grafting, autografts and allografts, can result in increased patient morbidity or a high rate of failure respectively. An ideal alternative would be a biodegradable tissue engineered graft that fulfills the function of bone while promoting the growth of new bone tissue. We developed a prevascularized tissue engineered scaffold of electrospun biodegradable polymers PLLA and PDLA reinforced with hydroxyapatite, a mineral similar to that found in bone. A composite design was utilized to mimic the structure and function of human trabecular and cortical bone. These scaffolds were characterized mechanically and in vitro to determine osteoinductive and angioinductive properties. It was observed that further reinforcement is necessary for the scaffolds to mechanically match bone, but the scaffolds are successful at inducing the differentiation of mesenchymal stem cells into mature bone cells and vascular endothelial cells. Prevascularization was seen to have a positive effect on angiogenesis and cellular metabolic activity, critical factors for the integration of a graft. [ABSTRACT FROM AUTHOR]

Chronic venous disease (CVD) is the most common reported chronic condition in the United States, affecting more than 25 million Americans. Regardless of its high occurrence, current therapeutic options are far from ideal due to their palliative nature. For best treatment outcomes, challenging cases of chronic venous insufficiency (CVI) are treated by repair or replacement of venous valves. Regrettably, the success of venous valve transplant is dependent on the availability of autologous venous valves and hindered by the possibility of donor site complications and increased patient morbidity. Therefore, the use of alternative tissue sources to provide off-the-shelf venous valve replacements has potential to be extremely beneficial to the field of CVI. This manuscript demonstrates the capability of producing off-the-shelf fully functional venous valved extracellular matrix (ECM) scaffold conduits from bovine saphenous vein (SV), using an antigen removal (AR) method. AR ECM scaffolds maintained native SV structure-function relationships and associated venous valves function. Conversely, SDS decellularization caused significant changes to the collagen and elastin macromolecular structures, resulting in collagen fibril merging, elimination of fibril crimp, amalgaming collagen fibers and fragmentation of the inner elastic lamina. ECM changes induced by SDS decellularization resulted in significant venous valve dysfunction. Venous valved conduits generated using the AR approach have potential to serve as off-the-shelf venous valve replacements for CVI. Retention of the structure and composition of extracellular matrix (ECM) proteins within xenogeneic scaffolds for tissue engineering is of crucial importance, due to the undeniable effect ECM proteins can impose on repopulating cells and function of the resultant biomaterial. This manuscript demonstrates that alteration or elimination of ECM proteins via commonly utilized decellularization approach results in complete disruption of venous valve function. Conversely, retention of the delicate ECM structure and composition of native venous tissue, using an antigen removal tissue processing method, results in preservation of native venous valve function. Image, graphical abstract [ABSTRACT FROM AUTHOR]

BACKGROUND: Tissue engineering technology provides an effective medical means to solve the problems of organ donor insufficiency and tissue trauma reconstruction. OBJECTIVE: To provide information reference for researchers of tissue engineering through the analysis of the patents data to grasp the hotspot and core technologies of tissue engineering. METHODS: The information including the annual distribution of patents, priority countries, patentees, hotspot of technology and core patents by Excel after extracting the data by programming based on Derwent Innovations Index. RESULTS AND CONCLUSION: In the past decade, the number of patents in the field of tissue engineering is on a rise. The most prolific countries are the United States, China and Japan. Zhejiang University, Donghua University, and the University of California are the leading institutions. Two United States companies, TYCO HEALTHCARE GROUP LP and ETHICON INC, each have two of the 20 core patents. The market of the relevant tissue-engineered products is led by the United States. Scaffolds, tissue engineering technology and prosthesis are the hot areas of tissue engineering. Scaffold materials, extracellular matrix, drug delivery, construction technology, and devices are the core technologies in the field of tissue engineering. [ABSTRACT FROM AUTHOR]

Biomaterials research output has experienced an exponential increase over the last three decades. The majority of research is published in the form of scientific articles and is therefore available as unstructured text, making it a challenging input for computational processing. Computational tools are becoming essential to overcome this information overload. Among them, text mining systems present an attractive option for the automated extraction of information from text documents into structured datasets. This work presents the first automated system for biomaterial related information extraction from the National Library of Medicine's premier bibliographic database (MEDLINE) research abstracts into a searchable database. The system is a text mining pipeline that periodically retrieves abstracts from PubMed and identifies research and clinical studies of biomaterials. Thereafter, the pipeline identifies sixteen concept types of interest in the abstract using the Biomaterials Annotator, a tool for biomaterials Named Entity Recognition (NER). These concepts of interest, along with the abstract and relevant metadata are then deposited in DEBBIE, the Database of Experimental Biomaterials and their Biological Effect. DEBBIE is accessible through a web application that provides keyword searches and displays results in an intuitive and meaningful manner, aiming to facilitate an efficient mapping and organization of biomaterials information., (© 2023 Wiley-VCH GmbH.)

With greater than 500,000 orthopaedic procedures performed in the United States each year requiring a bone graft, the development of novel graft materials is necessary. We report that some porous polymer/ceramic composite scaffolds possess intrinsic osteoinductivity as shown through their capacity to induce in vivo host osteoid mineralization and in vitro stem cell osteogenesis making them attractive synthetic bone graft substitutes. It was discovered that certain low crystallinity ceramics partially dissociate into simple signaling molecules (i.e., calcium and phosphate ions) that induce stem cells to endogenously produce their own osteoinductive proteins. Review of the literature has uncovered a variety of simple signaling molecules (i.e., gases, ions, and redox reagents) capable of inducing other desirable stem cell differentiation through endogenous growth factor production. Inductive simple signaling molecules, which we have termed inducerons, represent a paradigm shift in the field of regenerative engineering where they can be utilized in place of recombinant protein growth factors. [ABSTRACT FROM AUTHOR]

Abstract: In the United States, more than 2600 kidneys are discarded annually, from the total number of kidneys procured for transplant. We hypothesized that this organ pool may be used as a platform for renal bioengineering and regeneration research. We previously showed that decellularization of porcine kidneys yields renal extracellular matrix (ECM) scaffolds that maintain their basic components, support cell growth and welfare in vitro and in vivo, and show an intact vasculature that, when such scaffolds are implanted in vivo, is able to sustain physiological blood pressure. The purpose of the current study was to test if the same strategy can be applied to discarded human kidneys in order to obtain human renal ECM scaffolds. The results show that the sodium dodecylsulfate-based decellularization protocol completely cleared the cellular compartment in these kidneys, while the innate ECM framework retained its architecture and biochemical properties. Samples of human renal ECM scaffolds stimulated angiogenesis in a chick chorioallantoic membrane assay. Importantly, the innate vascular network in the human renal ECM scaffolds retained its compliance. Collectively, these results indicate that discarded human kidneys are a suitable source of renal scaffolds and their use for tissue engineering applications may be more clinically applicable than kidneys derived from animals. [Copyright &y& Elsevier]

Abstract: Magnetic resonance imaging (MRI) studies of tissue engineered constructs prior to implantation clearly demonstrate the utility of the MRI technique for studying the bone formation process. To test the utility of our MRI protocols for explant studies, we present a novel test platform in which osteoblast-seeded scaffolds were implanted on the chorioallantoic membrane of a chick embryo. Scaffolds from the following experimental groups were examined by high-resolution MRI: (a) cell-seeded implanted scaffolds (CIM), (b) unseeded implanted scaffolds (UCIM), (c) cell-seeded scaffolds in static culture (CIV) and (d) unseeded scaffolds in static culture (UCIV). The reduction in water proton transverse relaxation times and the concomitant increase in water proton magnetization transfer ratios for CIM and CIV scaffolds, compared to UCIV scaffolds, were consistent with the formation of a bone-like tissue within the polymer scaffold, which was confirmed by immunohistochemistry and fluorescence microscopy. However, the presence of angiogenic vessels and fibrotic adhesions around UCIM scaffolds can confound MRI findings of bone deposition. Consequently, to improve the specificity of the MRI technique for detecting mineralized deposits within explanted tissue engineered bone constructs, we introduce a novel contrast agent that uses alendronate to target a Food and Drug Administration-approved MRI contrast agent (Gd-DOTA) to bone mineral. Our contrast agent termed GdALN was used to uniquely identify mineralized deposits in representative samples from our four experimental groups. After GdALN treatment, both CIM and CIV scaffolds, containing mineralized deposits, showed marked signal enhancement on longitudinal relaxation time-weighted (T1W) images compared to UCIV scaffolds. Relative to UCIV scaffolds, some enhancement was observed in T1W images of GdALN-treated UCIM scaffolds, subjacent to the dark adhesions at the scaffold surface, possibly from dystrophic mineral formed in the fibrotic adhesions. Notably, residual dark areas on T1W images of CIM and UCIM scaffolds were attributable to blood inside infiltrating vessels. In summary, we present the efficacy of GdALN for sensitizing the MRI technique to the deposition of mineralized deposits in explanted polymeric scaffolds. [Copyright &y& Elsevier]

AbstractViruses of the genus Flavivirus are responsible for significant human disease and mortality. The N-terminal domain of the flaviviral nonstructural (NS)3 protein codes for the serine, chymotrypsin-fold proteinase (NS3pro). The presence of thenonstructural (NS)2B cofactor, which is encoded by the upstream gene in the flaviviral genome, is necessary for NS3pro to exhibit its proteolytic activity. The two-component NS2B-NS3pro functional activity is essential for the viral polyprotein processing and replication. Both the structure and the function of NS2B-NS3pro are conserved in the Flavivirus family. Because of its essential function in the posttranslational processing of the viral polyprotein precursor, NS2B-NS3pro is a promising target for anti-flavivirus drugs. To identify selective inhibitors with the reduced cross-reactivity and off-target effects, we focused our strategy on the allosteric inhibitors capable of targeting the NS2B-NS3pro interface rather than the NS3pro active site. Using virtual ligand screening of the diverse, ∼275,000-compound library and the catalytic domain of the two-component West Nile virus (WNV) NS2B-NS3pro as a receptor, we identified a limited subset of the novel inhibitory scaffolds. Several of the discovered compounds performed as allosteric inhibitors and exhibited a nanomolar range potency in thein vitro cleavage assays. The inhibitors were also potent in cell-based assays employing the sub-genomic, luciferase-tagged WNV and Dengue viral replicons. The selectivity of the inhibitors was confirmed using thein vitro cleavage assays with furin, a human serine proteinase, the substrate preferences of which are similar to those of WNV NS2B-NS3pro. Conceptually, the similarin silico drug discovery strategy may be readily employed for the identification of inhibitors of other flaviviruses. [ABSTRACT FROM AUTHOR]

Recent advancements in the bioinks and three-dimensional (3D) bioprinting methods used to fabricate vascular constructs are summarized herein. Critical biomechanical properties required to fabricate an ideal vascular graft are highlighted, as well as various testing methods have been outlined to evaluate the bio-fabricated grafts as per the Food and Drug Administration (FDA) and International Organization for Standardization (ISO) guidelines. Occlusive artery disease and cardiovascular disease are the major causes of death globally. These diseases are caused by the blockage in the arteries, which results in a decreased blood flow to the tissues of major organs in the body, such as the heart. Bypass surgery is often performed using a vascular graft to re-route the blood flow. Autologous grafts represent a gold standard for such bypass surgeries; however, these grafts may be unavailable due to the previous harvesting or possess a poor quality. Synthetic grafts serve well for medium to large-sized vessels, but they fail when used to replace small-diameter vessels, generally smaller than 6 mm. Various tissue engineering approaches have been used to address the urgent need for vascular graft that can withstand hemodynamic blood pressure and has the ability to grow and remodel. Among these approaches, 3D bioprinting offers an attractive solution to construct patient-specific vessel grafts with layered biomimetic structures., (Creative Commons Attribution license.)

Spinal cord injury (SCI) is a disease of the central nervous system (CNS) that has not yet been treated successfully. In the United States, almost 450,000 people suffer from SCI. Despite the development of many clinical treatments, therapeutics are still at an early stage for a successful bridging of damaged nerve spaces and complete recovery of nerve functions. Biomimetic 3D scaffolds have been an effective option in repairing the damaged nervous system. 3D scaffolds allow improved host tissue engraftment and new tissue development by supplying physical support to ease cell function. Recently, 3D bioprinting techniques that may easily regulate the dimension and shape of the 3D tissue scaffold and are capable of producing scaffolds with cells have attracted attention. Production of biologically more complex microstructures can be achieved by using 3D bioprinting technology. Particularly in vitro modeling of CNS tissues for in vivo transplantation is critical in the treatment of SCI. Considering the potential impact of 3D bioprinting technology on neural studies, this review focus on 3D bioprinting methods, bio-inks, and cells widely used in neural tissue engineering and the latest technological applications of bioprinting of nerve tissues for the repair of SCI are discussed. • 3D bioprinting applications for spinal cord injury repair • Different 3D bioprinting technologies on neural tissue engineering • 3D bioprinted scaffold for neural tissue engineering [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disease in the United States after Alzheimer's disease (AD). To help understand the electrophysiology of these diseases, N27 neuronal cells have been used as an in vitro model. In this study, a flexible graphene-based biosensor design is presented. Biocompatible graphene was manufactured using a liquid-phase exfoliation method and bovine serum albumin (BSA) for further exfoliation. Raman spectroscopy results indicated that the graphene produced was indeed few-layer graphene (FLG) with (I D / I G) G r a p h e n e = 0.11. Inkjet printing of this few-layer graphene ink onto Kapton polyimide (PI) followed by characterization via scanning electron microscopy (SEM) showed an average width of ≈868 µm with a normal thickness of ≈5.20 µm. Neuronal cells were placed on a thermally annealed 3D printed graphene chip. A live–dead cell assay was performed to prove the biosensor biocompatibility. A cell viability of approximately 80% was observed over 96 h, which indicates that annealed graphene on Kapton PI substrate could be used as a neuronal cell biosensor. This research will help us move forward with the study of N27 cell electrophysiology and electrical signaling. [ABSTRACT FROM AUTHOR]

Graphene, with excellent conductivity can promote the growth and differentiation of neural stem cells (NSCs), but the rigidity has limited its direct application in neural tissue engineering. In this study, waterborne biodegradable polyurethane (PU) was used as the matrix for the graphene nanocomposite materials to make graphene applicable to biocompatible scaffolds. The graphene sheets were observed on the surface of the composites which contained 5 wt % graphene (PU-G5). The nanocomposite retained the positive effect of graphene on cell behavior, while PU was flexible enough for further fabrication. Endothelial cells (ECs) and NSCs cocultured on the nanocomposite became more vascular-like and glial-like without induction culture medium. The specific vascular-related and neural-related gene markers, KDR, VE-Cadherin, and GFAP, were upregulated more than twice as the content of graphene increased (5 wt %). The fibrous capsule of the PU-G5 film group was about 38 μm in thickness in subcutaneous implantation, which was only half that of the graphene-free group. Nerve conduits made of the PU-graphene nanocomposite were found to promote the regeneration of the peripheral nerve in a rat sciatic nerve 10 mm gap transection model. In particular, the regenerated tissue in PU-G5 conduits showed an obvious response peak in the compound action potential (CAP) examination and had a similar CAP wave pattern to that of the normal sciatic nerve. However, such a response was not observed in the PU group. The nerve conduit made of PU-G5 had 72% and 50% enhancement on the numbers of axons and blood vessels of regenerated tissue, respectively. The regenerated area of nerve in PU-G5 was 25% larger than that in pristine PU. Compared with the U.S. Food and Drug Administration (FDA) approved conduit, Neurotube, the regenerated nerve in PU-G5 was 1.7 times more than that in Neurotube. In addition to the fast recovery rate, the ability to regenerate tissue with normal morphology is a significant finding of this study that may lead to clinical applications in the future. PU-graphene nanocomposites thus have potential applications in neural tissue engineering.

The field of bioprinting is rapidly evolving as researchers innovate and drive the field forward. This chapter provides a brief overview of the history of bioprinting from the first described printer system in the early 2000s to present-day relatively inexpensive commercially available units and considers the current state of the field and emerging trends, including selected applications and techniques.

Background: Properly designed biodegradable scaffolds facilitate repair or regeneration of stromal tissues. Over the past 50 years, a variety of synthetic, semisynthetic, and decellularized scaffolds have been developed that provide surgeons with tools to reconstruct a wide array of structural defects., Methods: The authors review the literature of biological degradable scaffolds in current clinical use in the United States and highlight their design principles and products in common use., Results: Host tissues populate scaffolds with inflammatory cells, fibroblasts, blood vessels, nerves, and lymphatics. Cells lay down extracellular matrix macromolecules, whereas enzymes degrade the scaffold. Over time, the scaffold can be totally replaced by host tissues., Conclusions: The greatest use of scaffolds in plastic surgery is in skin replacement, breast reconstruction, abdominal wall reconstruction, and peripheral nerve repair. Other areas of importance are cartilage and bone replacement and support for lining replacements such as bowel, bladder, mucosa, and dura. The wide range of research being performed in this field is likely to provide surgeons with more choices and improved materials to repair and regenerate stromal structures.

One of the novel and progressive technology employed in pharmaceutical manufacturing, design of medical device and tissue engineering is three-dimensional (3D) printing. 3D printing technologies provide great advantages in 3D scaffolds fabrication over traditional methods in the control of pore size, porosity, and interconnectivity. Various techniques of 3D-printing include powder bed fusion, fused deposition modeling, binder deposition, inkjet printing, photopolymerization and many others which are still evolving. 3D-printing technique been employed in developing immediate release products, various systems to deliver multiple release modalities etc. 3D printing has opened the door for new generation of customized drug delivery with built-in flexibility for safer and effective therapy. Our mini-review provides a quick snapshot on an overview of 3D printing, various techniques employed, applications and its advancements in pharmaceutical sciences.

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.

Treatment of combat injuries and resulting wounds can be difficult to treat due to compromised and evolving tissue necrosis, environmental contaminants, multidrug resistant microbacterial and/or fungal infections, coupled with microvascular damage and/or hypovascularized exposed vital structures. Our group has developed surgical care algorithms with identifiable salvage techniques to achieve stable, definitive wound coverage often with the aid of certain regenerative medicine biologic scaffold materials and advanced wound care to facilitate tissue coverage and healing. This case series reports on the role of urinary bladder matrix scaffolds in the wound care and reconstruction of traumatic and combat wounds. Urinary bladder matrix was found to facilitate definitive soft tissue reconstruction by establishing a neovascularized soft tissue base acceptable for second stage wound and skin coverage options within traumatic and combat-related wounds.

The vast majority of arteriovenous grafts (AVG) have been constructed using expanded polytetrafluoroethylene (ePTFE). While ePTFE grafts have the advantage of being relatively inexpensive and easy to manufacture, distribute, ship, and store, their primary patency rates are disappointing when compared with the native AVF. Though use of arteriovenous fistulas (AVF) in the United States has increased substantially, approximately 25% of hemodialysis patients continue to use AVG as their vascular access. We present here a comprehensive review of biological grafts and their use in hemodialysis vascular access. In this review, we discuss the use of synthetics and then explore the evolution of biological grafts over the past 20 years, their clinical impact, and future challenges in widespread clinical use in hemodialysis patients. Provided are in depth descriptions of currently used nonbiological arteriovenous grafts and the recent approaches in increasing the patency of synthetic grafts. Recent technological advances using tissue-engineered AVGs have shown promise for patients receiving hemodialysis and their potential to provide an attractive, viable option for vascular access have been discussed., (© 2012 Wiley Periodicals, Inc.)

For decades, there has been an ongoing controversy regarding the need for an "adequate" width of keratinized gingiva/mucosa to preserve periodontal and implant health. Today, the presence of a certain width of keratinized tissue is recommended for achieving long-term periodontal and implant success, and therefore, a new collagen matrix has been developed to enhance the width of keratinized gingiva/mucosa. During postextraction socket preservation, guided bone regeneration techniques require complete coverage of the barrier membrane to reduce the risk of infection, occasionally causing a reduction of the width of keratinized tissue. Using the new collagen matrix, it is possible to leave the membrane intentionally uncovered, without suturing the surgical flap above it, to avoid the reduction of such tissue.

The use of tissue-engineering methods to create autologous heart valve constructs has the potential to overcome the fundamental drawbacks of more traditional valve prostheses. Traditional mechanical valves, while durable, increase the risk for endocarditis and thrombogenesis, and require the recipient to continue lifelong anticoagulant therapy. Homograft or xenograft heart valve prostheses are associated with immune reaction and progressive deterioration with limited durability. Most importantly, neither option is capable of growth and remodeling in vivo and both options place the patient at risk for valve-related complications and reoperation. These shortcomings have prompted the application of tissue-engineering techniques to create fully autologous heart valve replacements. Future clinically efficacious tissue-engineered autologous valves should be nonthrombogenic, biocompatible, capable of growth and remodeling in vivo, implantable with current surgical techniques, hemodynamically perfect, durable for the patient's life and most importantly, significantly improve quality of life for the patient. In order to meet these expectations, the nature of the ideal biochemical milieu for conditioning an autologous heart valve will need to be elucidated. In addition, standardized criteria by which to quantitatively evaluate a tissue-engineered heart valve, as well as noninvasive analytical techniques for use in long-term animal models, will be required. This article highlights the advances, challenges and future clinical prospects in the field of tissue engineering of autologous heart valves, focusing on progress made by studies that have investigated a fully autologous, tissue-engineered pulmonary valve replacement in vivo.

Over the past 2 decades there has been significant progress in the treatment of articular cartilage pathology with the introduction of cell biology, tissue engineering, and biomaterials to address long standing challenges in this debilitating condition. However, cell therapies and products combining cells, other biologics, devices, and/or drugs do not easily fit within traditional regulatory frameworks of the US Food and Drug Administration (FDA) or agencies outside the United States. Regulations have evolved to specifically address these types of products in terms of their unique scientific and clinical issues. This paper reviews the characteristics of cell and combination products that distinguish them from more traditional medical devices and drugs, FDA regulatory pathways for marketing approval of these new types of products, and the implications of these regulations for orthopedic product development and practice.

Several absorbable nerve conduits are approved by the US Food and Drug Administration (FDA) and Conformit Europe (CE) for clinical repair of peripheral and cranial nerves . Surgeons are often not aware of the different(bio) materials of these conduits when performing nerve repair. An overview of these FDA- and CE-approved absorbable nerve conduits for clinical use is presented . PubMed, MEDLINE, and the companies selling the conduits were consulted . The available FDA and CE absorbable nerve conduits for peripheral and cranial nerve repair are 2 collagen- and 2 synthetic- polyester based conduits. The available clinical data, the price, the length, and the composition of the tube show significant differences. Based on the available data in this paper at this moment, we favor the PGA (Neurotube) nerve conduit for repair of peripheral and cranial nerve defects because of its advantages in length, price, and availability of clinical data. However, no prospective studies comparing the available nerve conduits have been published.

Several absorbable nerve conduits are approved by the US Food and Drug Administration (FDA) and Conformit Europe (CE) for clinical repair of peripheral and cranial nerves. Surgeons are often not aware of the different (bio)materials of these conduits when performing nerve repair. An overview of these FDA- and CE-approved absorbable nerve conduits for clinical use is presented. PubMed, MEDLINE, and the companies selling the conduits were consulted. The available FDA and CE absorbable nerve conduits for peripheral and cranial nerve repair are 2 collagen- and 2 synthetic-polyester-based conduits. The available clinical data, the price, the length, and the composition of the tube show significant differences. Based on the available data in this paper at this moment, we favor the PGA (Neurotube) nerve conduit for repair of peripheral and cranial nerve defects because of its advantages in length, price, and availability of clinical data. However, no prospective studies comparing the available nerve conduits have been published.