Project description:Treatments for temporomandibular joint (TMJ) disc thinning and perforation, conditions prevalent in TMJ pathologies, are palliative but not reparative. To address this, scaffold-free tissue-engineered implants were created using allogeneic, passaged costal chondrocytes. A combination of compressive and bioactive stimulation regimens produced implants with mechanical properties akin to those of the native disc. Efficacy in repairing disc thinning was examined in minipigs. Compared to empty controls, treatment with tissue-engineered implants restored disc integrity by inducing 4.4 times more complete defect closure, formed 3.4-fold stiffer repair tissue, and promoted 3.2-fold stiffer intralaminar fusion. The osteoarthritis score (indicative of degenerative changes) of the untreated group was 3.0-fold of the implant-treated group. This tissue engineering strategy paves the way for developing tissue-engineered implants as clinical treatments for TMJ disc thinning.
Project description:Neuroblastoma is the most common extracranial solid tumor of childhood, and the outcomes for children with high-risk and relapsed disease remain poor. However, new international strategies for risk stratification and for treatment based on novel tumor targets and including immunotherapy are being employed in attempts to improve the outcomes of children with neuroblastoma. A new international neuroblastoma risk classification system has been developed which is being incorporated into cooperative group clinical trials in North America, Japan, and Europe, resulting in standardized approaches for the initial evaluation and treatment stratification of neuroblastoma patients. Furthermore, novel treatment regimens are being developed based on improved understanding of neuroblastoma biology and on the recruitment of the immune system to specifically target neuroblastoma tumors. These approaches will lead to new therapeutic strategies that likely will improve the outcomes for children with neuroblastoma worldwide.
Project description:Tissue engineering is defined as the combination of biomaterials and bioengineering principles together with cell transplantation or directed growth of host cells to develop a biological replacement tissue or organ that can be a substitute for normal tissue both in structure and function. Despite early promising preclinical studies, clinical translation of tissue engineering in pediatric urology into humans has been unsuccessful both for cell-seeded and acellular scaffolds. This can be ascribed to various factors, including the use of only non-diseased models that inaccurately describe the structural and functional modifications of diseased tissue. The paper addresses potential future strategies to overcome the limitations experienced in clinical applications so far. This includes the use of stem cells of various origins (mesenchymal stem cells, hematopoietic stem/progenitor cells, urine-derived stem cells, and progenitor cells of the urothelium) as well as the need for a deeper understanding of signaling pathways and directing tissue ingrowth and differentiation through the concept of dynamic reciprocity. The development of smart scaffolds that release trophic factors in a set and timely manner will probably improve regeneration. Modulation of innate immune response as a major contributor to tissue regeneration outcome is also addressed. It is unlikely that only one of these strategies alone will lead to clinically applicable tissue engineering strategies in pediatric urology. In the meanwhile, the fundamental new insights into regenerative processes already obtained in the attempts of tissue engineering of the lower urogenital tract remain our greatest gain.
Project description:Adult stem cells that are tightly regulated by the specific microenvironment, or the stem cell niche, function to maintain tissue homeostasis and regeneration after damage. This demands the existence of specific niche components that can preserve the stem cell pool in injured tissues and restore the microenvironment for their subsequent appropriate functioning. This role may belong to mesenchymal stromal cells (MSCs) due to their resistance to damage signals and potency to be specifically activated in response to tissue injury and promote regeneration by different mechanisms. Increased amount of data indicate that activated MSCs are able to produce factors such as extracellular matrix components, growth factors, extracellular vesicles and organelles, which transiently substitute the regulatory signals from missing niche cells and restrict the injury-induced responses of them. MSCs may recruit functional cells into a niche or differentiate into missing cell components to endow a niche with ability to regulate stem cell fates. They may also promote the dedifferentiation of committed cells to re-establish a pool of functional stem cells after injury. Accumulated evidence indicates the therapeutic promise of MSCs for stimulating tissue regeneration, but the benefits of administered MSCs demonstrated in many injury models are less than expected in clinical studies. This emphasizes the importance of considering the mechanisms of endogenous MSC functioning for the development of effective approaches to their pharmacological activation or mimicking their effects. To achieve this goal, we integrate the current ideas on the contribution of MSCs in restoring the stem cell niches after damage and thereby tissue regeneration.
Project description:Stem/progenitor cells are undifferentiated cells characterized by their exclusive ability for self-renewal and multilineage differentiation potential. In recent years, researchers and investigations explored the prospect of employing stem/progenitor cell therapy in regenerative medicine, especially stem/progenitor cells originating from the oral tissues. In this context, the regeneration of the lost dental tissues including enamel, dentin, and the dental pulp are pivotal targets for stem/progenitor cell therapy. The present review elaborates on the different sources of stem/progenitor cells and their potential clinical applications to regenerate enamel, dentin, and the dental pulpal tissues.
Project description:Intervertebral disc (IVD) is an avascular tissue which contributes to the weight bearing, motion, and flexibility of spine. However, IVD is susceptible to damage and even failure due to injury, pathology, and aging. Annulus fibrosus (AF), the structural and functional integrity of which is critically essential to confine nucleus pulpous (NP) and maintain physiological intradiscal pressure under mechanical loading, plays a critical role in the biomechanical properties of IVD. AF degeneration commonly results in substantial deterioration of IVD. During this process, the biomechanical properties of AF and the balance between anabolism and catabolism in IVD are progressively disrupted, leading to chronic back pain, and even disability of individuals. Therefore, repairing and regenerating AF are effective treatments to degeneration-associated pains. However, they remain highly challenging due to the complexity of natural AF tissue in the aspects of cell phenotype, biochemical composition, microstructure, and mechanical properties. Tissue engineering (TE), by combining biological science and materials engineering, shed lights on AF regeneration. In this article, we review recent advances in the pro-anabolic approaches in the form of cell delivery, bioactive factors delivery, gene therapy, and TE strategies for achieving AF regeneration.
Project description:Regenerating lost or damaged tissue is the primary goal of Tissue Engineering. 3D bioprinting technologies have been widely applied in many research areas of tissue regeneration and disease modeling with unprecedented spatial resolution and tissue-like complexity. However, the extraction of tissue architecture and the generation of high-resolution blueprints are challenging tasks for tissue regeneration. Traditionally, such spatial information is obtained from a collection of microscopic images and then combined together to visualize regions of interest. To fabricate such engineered tissues, rendered microscopic images are transformed to code to inform a 3D bioprinting process. If this process is augmented with data-driven approaches and streamlined with machine intelligence, identification of an optimal blueprint can become an achievable task for functional tissue regeneration. In this review, our perspective is guided by an emerging paradigm to generate a blueprint for regeneration with machine intelligence. First, we reviewed recent articles with respect to our perspective for machine intelligence-driven information retrieval and fabrication. After briefly introducing recent trends in information retrieval methods from publicly available data, our discussion is focused on recent works that use machine intelligence to discover tissue architectures from imaging and spectral data. Then, our focus is on utilizing optimization approaches to increase print fidelity and enhance biomimicry with machine learning (ML) strategies to acquire a blueprint ready for 3D bioprinting.
Project description:Recent advancements in the field of musculoskeletal tissue engineering have raised an increasing interest in the regeneration of the anterior cruciate ligament (ACL). It is the aim of this article to review the current research efforts and highlight promising tissue engineering strategies. The four main components of tissue engineering also apply in several ACL regeneration research efforts. Scaffolds from biological materials, biodegradable polymers and composite materials are used. The main cell sources are mesenchymal stem cells and ACL fibroblasts. In addition, growth factors and mechanical stimuli are applied. So far, the regenerated ACL constructs have been tested in a few animal studies and the results are encouraging. The different strategies, from in vitro ACL regeneration in bioreactor systems to bio-enhanced repair and regeneration, are under constant development. We expect considerable progress in the near future that will result in a realistic option for ACL surgery soon.
Project description:Efficiency of cell-based tissue engineering and regenerative medicine has been limited by inadequate cellular responses to injury because of aging and poor controllability of cellular interactions. Since cell progression is under a tight epigenetic regulation, epigenetic modulators such as 5-azacytidine (5-Aza-CR) have been utilized to facilitate reprogramming and development of somatic cells in 2-dimensional (2-D) settings. Nonetheless, progression of a specific tissue lineage toward the terminal phenotype is dependent not only on the genomic potential, but also on the microenvironment cues that are beyond the capability of 2-D approaches. In this study, we investigated the combined effects of matrices of variable rigidities and the treatment with the epigenetic modulator 5-Aza-CR on reprogramming adipose-derived stromal cells (ADSCs) into myoblast-like cells by utilizing tunable transglutaminase cross-linked gelatin (Col-Tgel) in vitro and in vivo. Our experiments demonstrated that cellular plasticity and trans-differentiation were significantly enhanced when ADSCs were treated with an effective dose of 5-Aza-CR (1.25 to 12.5?ng) in the optimal myogenic matrix (15?±?5?kPa Col-Tgel). Our findings suggest that both physical signals and chemical milieu are critical for the regulation of cellular responses.
Project description:The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental "origin" require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.