A major challenge in the management of patients suffering from diabetes is the risk of developing nonhealing foot ulcers. Most in vitro methods to screen drugs for wound healing therapies rely on conventional 2D cell cultures that do not closely mimic the complexity of the diabetic wound environment. In addition, while three-dimensional (3D) skin tissue models of human skin exist, they have not previously

For end-stage lung disease, lung transplantation remains the only treatment but is limited by the availability of organs. Production of bioengineered lungs via recellularization is an alternative but is hindered by inadequate repopulation. We present a cell delivery method via the generation of negative pressure. Decellularized lungs were seeded with human bronchial epithelial cells using gravity-based

Stem cell-derived, organotypic in vitro models, known as organoids, have emerged as superior alternatives to traditional cell culture models due to their unparalleled ability to recreate complex physiological and pathophysiological processes. For this reason, they are attractive targets of tissue-engineering efforts, as constructs that include organoid technology would be expected to better simulate

The classic bone tissue engineering model for bone regeneration combines three elements: scaffolds, biomaterials, and mesenchymal stem cells (MSCs). Incorporation of MSCs and growth factors into a scaffold implanted into the area of bone injury is a proven strategy to achieve successful bone regeneration as demonstrated in the literature. However, a major limitation of using bone grafts or scaffolds

Many children born with congenital heart disease need a heart valve repair or replacement. Currently available repair materials and valve replacements are incapable of growth, repair, and adaptation, rendering them inadequate for growing children. Heart valve tissue engineering (HVTE) aims to develop living replacement valves that can meet these needs. Among numerous cell sources for in vitro HVTE

3D Bioprinting is an emerging tissue engineering technology, already with several remarkable accomplishments and with more promises to fulfill. Besides the enduring goal of making tissues for implantation, it could also become an essential tool in the worldwide trend to replace animal experimentation with improved in vitro models for disease mechanism studies, or with new high-throughput pharmacological

Despite their large societal burden, the development of therapeutic treatments for neurodegenerative diseases has been relatively unsuccessful. This is in part due to a lack of representative experimental models that reveal fundamental aspects of human brain pathology. Recently, assays for in vitro modelling of the human central nervous system (CNS) have significantly improved with the development

In heart failure, cardiac fibrosis is the result of an adverse remodeling process. Collagen is continuously synthesized in the myocardium in an ongoing attempt of the heart to repair itself. The resulting collagen depositions act counterproductively, causing diastolic dysfunction and disturbing electrical conduction. Efforts to treat cardiac fibrosis specifically have not been successful and the molecular

Omics technologies, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, multi-omics, and integrated modalities, have greatly contributed to our understanding of various diseases by enabling researchers to probe the molecular wiring of cellular systems in a high-content and precise manner. With the development of tissue engineered 3D in vitro disease models, such as

Bioengineering of skin has been significantly explored, ranging from the use of traditional cell culture systems to the most recent organ-on-a-chip technology that permits skin modelling on physiological scales amongst other benefits. This paper presents key considerations for developing physiologically relevant immunocompetent diabetic foot ulcer models. Diabetic foot ulceration affects hundreds of

Osteoarthritis (OA) is a painful and disabling disease that affects millions of people worldwide. Symptom-alleviating treatments exist, although none with long-term efficacy. Furthermore, there are currently no disease-modifying OA drugs (DMOADs) with demonstrated efficacy in OA patients, which is, in part, attributed to a lack of full understanding of the pathogenesis of OA. The inability to translate

Notch is an evolutionary conserved cell-cell signaling pathway that is central in several biological processes, from tissue morphogenesis to homeostasis. It is therefore not surprising that several genetic mutations of Notch components cause inherited human diseases, especially cardiovascular disorders. Despite numerous efforts, current in vivo models are still insufficient to unravel the underlying

Juvenile idiopathic arthritis can affect the temporomandibular joint (TMJ) that can cause growth disturbances of the lower jaw (mandible). The collagen-induced arthritis (CIA) juvenile rat model may be an appropriate model for studying how juvenile arthritis affects this joint during growth. However, studies using this animal model to investigate TMJ arthritis are limited. To validate an animal model

Prominent clinical problems related to the skin-nerve interface include barrier dysfunction and erythema but it is the symptoms of pain and itch that lead patients to seek medical treatment. Tissue-engineered innervated skin models provide an excellent solution for studying the mechanisms underlying neuro-cutaneous disorders for drug screening, and cutaneous device development. Innervated skin substitutes

Dermis-isolated adult stem (DIAS) cells, abundantly available, are attractive for regenerative medicine. Strategies have been devised to isolate and to chondroinduce DIAS cells from various animals. This study aimed to characterize DIAS cells from human abdominal skin (human dermis-isolated adult stem [hDIAS] cells) and to compare and to refine various chondroinduction regimens to form functional neocartilage

Porous materials containing cells—prepared via cell seeding on scaffolds or gelation of cell-containing solutions—have been widely studied to investigate tissue regeneration and three-dimensional cultures. However, these methods cannot introduce cells into porous materials that have low water absorption or scaffolds that require cytotoxic solvents or processes for their production. In this study, first

Any significant in vitro evaluation of cartilage tissue engineering and cartilage repair strategies has to be performed under the harsh conditions encountered in vivo within synovial joints. To this end, we have developed a novel automated physiological robot reactor system (PRRS) that is capable of recapitulating complex physiological motions and load patterns within an environment similar to that

Quantifying fiber diameter is important for characterizing electrospun polymer scaffolds. Many researchers use manual measurement methods, which can be time-consuming and variable. Semi-automated tools exist, but there is room for improvement. The current work used Matlab to develop an image analysis program to quickly and consistently measure fiber diameter in scanning electron micrographs. The new

Recent biotechnical advances in the in vitro culture of cholangiocytes and generation of bioengineered biliary tissue have a high potential for creating biliary tissue to be used for disease modeling, drug screening and transplantation. For the past few decades, scientists have searched for a source of cholangiocytes, focused on primary cholangiocytes or cholangiocytes derived from hepatocytes or stem

Osteochondral tissue repair represents a common clinical need, with multiple approaches in tissue engineering and regenerative medicine being investigated for the repair of defects of articular cartilage and subchondral bone. A full thickness rabbit femoral condyle defect is a clinically relevant model of an articulating and load bearing joint surface for the investigation of osteochondral tissue repair

Intervertebral disc (IVD) degeneration is a major cause of back pain. Current surgical interventions have limitations. An alternative approach is to replace degenerated IVDs with a natural biological scaffold. The removal of cellular components from human IVDs should render them nonimmunogenic upon implantation. The aim of this initial proof of technical feasibility study was to develop a decellularization

Despite considerable research effort, there is a significant need for safe agents that stimulate bone formation. Treatment of large or complex bone defects remains a challenge. Implantation of small molecule-induced human bone marrow-derived mesenchymal stromal cells (hBMSCs) on an appropriate tricalcium phosphate (TCP) scaffold offers a robust system for noninvasive therapy for spinal fusion. To show

Tracheal tissue engineering has become an active area of interest among clinical and scientific communities; however, methods to evaluate success of in vivo tissue-engineered solutions remain primarily qualitative. These evaluation methods have generally relied on the use of photographs to qualitatively demonstrate tracheal patency, endoscopy to image healing over time, and histology to determine the

Tendon injuries are difficult to heal, in part, because intrinsic tendon healing, which is dominated by scar tissue formation, does not effectively regenerate the native structure and function of healthy tendon. Further, many current treatment strategies also fall short of producing regenerated tendon with the native properties of healthy tendon. There is increasing interest in the use of cell-instructive

Background: Three-dimensional (3D) printing using melt electrowriting (MEW) technology is a recently developed technique to produce biocompatible micron-level mesh scaffolds layer-by-layer that can be seeded with cells for tissue engineering. Examining cell behavior, such as growth rate and migration, can be problematic in these opaque 3D scaffolds. A straightforward and quantitative method was developed

Identification of matrix-bound nanovesicles (MBV) as ubiquitous components of the extracellular matrix (ECM) raises questions regarding their biologic functions and their potential theranostic application. Unlike liquid-phase extracellular vesicles (e.g., exosomes), MBV are tightly bound to the ECM, which makes their isolation and harvesting more challenging. The indiscriminate use of different methods

Background: Limbal stem cell deficiency (LSCD) is a refractory ocular surface disorder characterized by progressive corneal epithelial degeneration, conjunctivalization, and neovascularization, potentially leading to blindness. There are currently no effective therapeutic options for patients experiencing routine symptomatic treatment failure. Transplantation of amniotic membrane (AM) with adherent

The use of animal models along with the employment of advanced and sophisticated stereological methods for assessing bone quality combined with the use of statistical methods to evaluate the effectiveness of bone therapies has made it possible to investigate the pathways that regulate bone responses to medical devices. Image analysis of histomorphometric measurements remains a time-consuming task,

In vitro tissue-engineered cell culture models are an essential instrument to investigate physiological and pathophysiological wound healing mechanisms and to evaluate new beneficial wound dressing materials and therapeutics to identify possible drug targets and to improve regeneration processes in nonhealing and chronic wounds. In this study, the authors established an in vitro model for cutaneous

Three-dimensional (3D) cardiac tissue reconstruction using tissue engineering technology is a rapidly growing area of regenerative medicine and drug screening development. However, there remains an urgent need for the development of a method capable of accurately measuring the contractile force of physiologically relevant 3D myocardial tissues to facilitate the prediction of human heart tissue drug

Background: The fabrication of artificial cardiac tissue is an active area of research due to the shortage of donors for heart transplantation and for drug development. In our previous study, we fabricated vascularized three-dimensional (3D) cardiac tissue by layer-by-layer (LbL) and cell accumulation technique. However, it was not able to develop sufficient function because it was cultured on a hard

In vivo liver decellularization has become a promising strategy to study in vivo liver engineering. However, long-term survival after in vivo liver decellularization has not yet been achieved due to anatomical and technical challenges. This study aimed at establishing a survival model of in vivo partial liver lobe perfusion-decellularization in rats. We compared three decellularization protocols (1%

Hydrogel microspheres have been widely used as cell carriers and three-dimensional cell culture matrices. However, these microspheres are associated with several unfavorable properties for bone tissue engineering applications, for example, their surface is too smooth to attach cells and they do not contain inorganic materials. This article presents a new method to overcome these disadvantages by depositing

Retinal pigment epithelium (RPE) differentiated from human induced pluripotent stem cells, called induced retinal pigment epithelium (iRPE), is being explored as a cell-based therapy for the treatment of retinal degenerative diseases, especially age-related macular degeneration. The success of RPE implantation is linked to the use of biomimetic scaffolds that simulate Bruch's membrane and promote RPE

Repairing mandibular bone defects after radiotherapy of the upper aerodigestive tract is clinically challenging. Although bone tissue engineering has recently generated a number of innovative treatment approaches for osteoradionecrosis (ORN), these modalities must be evaluated preclinically in a relevant, reproducible, animal model. The objective of this study was to evaluate a novel rat model of mandibular

This study aimed at designing a novel electrospun scaffolding material that structurally and chemically resembles native extracellular matrix for bone tissue engineering. Calcium chloride-complexed polyamide66 (PA66/CaCl2) and pure PA66 electrospun nanofibers were fabricated by the electrospinning method. Scanning electron microscopy, X-ray diffraction, and Fourier transform infrared (FTIR) spectroscopy

Engineered scaffolds used to regenerate mammalian tissues should recapitulate the underlying fibrous architecture of native tissue to achieve comparable function. Current fibrous scaffold fabrication processes, such as electrospinning and three-dimensional (3D) printing, possess application-specific advantages, but they are limited either by achievable fiber sizes and pore resolution, processing efficiency

Background: Clinically available cartilage, such as large-volume tissue-engineered cartilage, is urgently required for various clinical applications. Tissue engineering chamber (TEC) models are a promising organ-level strategy for efficient enlargement of cells or tissues within the chamber. The conventional TEC technology is not suitable for cartilage culture, because it lacks the necessary chondrogenic

The generation of vascularized mineralized tissues of complex geometry without the use of extrinsic growth factors or exogenous cells requires a large animal model to recapitulate the challenges seen in the clinic. The proposed versatile ovine model can be utilized to investigate the use of a customized bioreactor to generate mineralized tissue, matching the size and shape of a defect before transfer

In this study, we describe the additive manufacturing of porous three-dimensionally (3D) printed ceramic scaffolds prepared with hydroxyapatite (HA), β-tricalcium phosphate (β-TCP), or the combination of both with an extrusion-based process. The scaffolds were printed using a novel ceramic-based ink with reproducible printability and storability properties. After sintering at 1200°C, the scaffolds

Low-concentration gelatin methacryloyl (GelMA) hydrogels have been found to be promising cell-laden bioinks with excellent cell viability. Herein, we report a strategy that accurately deposits cell-containing bioinks at 5% (w/v) GelMA using extrusion three-dimensional (3D) bioprinting technology by utilizing its photo-crosslinkable and thermosensitive properties without the need for any sacrificial

Horseradish peroxidase (HRP) has been investigated as a catalyst to crosslink tissue-engineered hydrogels because of its mild reaction conditions and ability to modulate the mechanical properties of the matrix. Here, we report the results of the first study investigating the use of HRP to crosslink fibrin scaffolds. We examined the effect of varying HRP and hydrogen peroxide (H2O2) incorporation strategies

Hydrogels derived from decellularized lungs are promising materials for tissue engineering in the development of clinical therapies and for modeling the lung extracellular matrix (ECM) in vitro. Characterizing and controlling the resulting physical, biochemical, mechanical, and biologic properties of decellularized ECM (dECM) after enzymatic solubilization and gelation are thus of key interest. As

Human mesenchymal stem cells (hMSCs) have wide applications in regenerative medicine but their clinical translation is largely hindered by limited production capacity of current cell expansion regime. This study utilizes a novel dispersible and dissolvable porous microcarrier tablet, 3D TableTrix™, in stirred bioreactor to demonstrate a scalable expansion protocol for industrial manufacturing of hMSCs

Histological evaluation of healing tendons is primarily focused on monitoring restoration of longitudinal collagen alignment, although the elastic property of energy-storing flexor tendons is largely attributed to interfascicular sliding facilitated by the interfascicular matrix (IFM). The objectives of this study were to explore the utility of second harmonic generation (SHG) imaging to objectively

Objective: To evaluate a vitrification protocol from histology to gene expression to slow freezing.

Recently, many studies on the three-dimensional (3D) fabrication of cells have been performed. Under these circumstances, it is indispensable to develop the imaging technologies and methodologies for noninvasive visualization of 3D cells fabricated. The objective of this study is to develop the labeling method of human induced pluripotent stem (iPS) cells-derived 3D cartilage tissue with gelatin nanospheres

Horseradish peroxidase (HRP) has been investigated as a catalyst to crosslink tissue engineered hydrogels because of its mild reaction conditions and ability to modulate the mechanical properties of the matrix. Here we report the results of the first study investigating the use of HRP to crosslink fibrin scaffolds. We examined the effect of varying HRP and hydrogen peroxide (H2O2) incorporation strategies

Near infrared (NIR) spectroscopy using a fiber optic probe shows great promise for the nondestructive in situ monitoring of tissue engineered construct development; however, the NIR evaluation of matrix components in samples with high water content is challenging, as water absorbances overwhelm the spectra. In this study, we established approaches by which NIR spectroscopy can be used to select optimal

The objective of this study is to investigate the utility of gelatin hydrogel-fragmented fibers (GHFF) as a material to suppress the shrinkage of cell sheets, which often happens upon detaching from a culture plate. The GHFF were fabricated by cutting gelatin hydrogel nonwoven fabrics. MC3T3-E1 cells were simply mixed with different amounts of GHFF, followed by culturing to formulate the cell sheet

The use of decellularized tissues or organs as cell culture scaffolds has proven to be a promising approach for tissue engineering and regenerative medicine, as these decellularized tissues can provide the instructive niche for cell differentiation and functions. Cartilage is a largely avascular tissue with limited regenerative capacity. Lesions caused by arthritis can lead to severe cartilage degeneration

Native cardiac tissue is composed of heterogeneous cell populations that work cooperatively for proper tissue function; thus, engineered tissue models have moved toward incorporating multiple cardiac cell types in an effort to recapitulate native multicellular composition and organization. Cardiac tissue models composed of stem cell-derived cardiomyocytes (CMs) require inclusion of non-myocytes to

Several urological structures, such as the male urethra, have a tubular organization consisting of different layers. However, in severe urethral disease, urologists are limited to replacing solely the epithelial layer. In case of severe hypospadias and urethral stricture disease, the underlying supporting structure (the corpus spongiosum) is either absent or fibrotic, causing suboptimal vascularization

Innovative therapies combining gene-corrected stem cells and the production of bioengineered tissues to treat epidermolysis bullosa are emerging. However, quantitative tests to measure the adhesion forces between two highly viscoelastic substrates such as those found in bilayered bioengineered skin are needed and are still lacking. The objective of this study was to develop a mechanical test to measure