Restoring normal islet mass and function in type 1 diabetes through regenerative medicine and tissue engineering.

Type 1 diabetes is characterised by autoimmune-mediated destruction of pancreatic ß-cell mass. With the advent of insulin therapy a century ago, type 1 diabetes changed from a progressive, fatal disease to one that requires lifelong complex self-management. Replacing the lost ß-cell mass through transplantation has proven successful, but limited donor supply and need for lifelong immunosuppression restricts widespread use. In this Review, we highlight incremental advances over the past 20 years and remaining challenges in regenerative medicine approaches to restoring ß-cell mass and function in type 1 diabetes. We begin by summarising the role of endocrine islets in glucose homoeostasis and how this is altered in disease. We then discuss the potential regenerative capacity of the remaining islet cells and the utility of stem cell-derived ß-like cells to restore ß-cell function. We conclude with tissue engineering approaches that might improve the engraftment, function, and survival of ß-cell replacement therapies.

History and Trends of 3D Bioprinting.

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.

Recent Approaches for Angiogenesis in Search of Successful Tissue Engineering and Regeneration.

Angiogenesis plays a central role in human physiology from reproduction and fetal development to wound healing and tissue repair/regeneration. Clinically relevant therapies are needed for promoting angiogenesis in order to supply oxygen and nutrients after transplantation, thus relieving the symptoms of ischemia. Increase in angiogenesis can lead to the restoration of damaged tissues, thereby leading the way for successful tissue regeneration. Tissue regeneration is a broad field that has shown the convergence of various interdisciplinary fields, wherein living cells in conjugation with biomaterials have been tried and tested on to the human body. Although there is a prevalence of various approaches that hypothesize enhanced tissue regeneration via angiogenesis, none of them have been successful in gaining clinical relevance. Hence, the current review summarizes the recent cell-based and cell free (exosomes, extracellular vesicles, micro-RNAs) therapies, gene and biomaterial-based approaches that have been used for angiogenesis-mediated tissue regeneration and have been applied in treating disease models like ischemic heart, brain stroke, bone defects and corneal defects. This review also puts forward a concise report of the pre-clinical and clinical studies that have been performed so far; thereby presenting the credible impact of the development of biomaterials and their 3D concepts in the field of tissue engineering and regeneration, which would lead to the probable ways for heralding the successful future of angiogenesis-mediated approaches in the greater perspective of tissue engineering and regenerative medicine.

Biomaterials: Been There, Done That, and Evolving into the Future.

Biomaterials as we know them today had their origins in the late 1940s with off-the-shelf commercial polymers and metals. The evolution of materials for medical applications from these simple origins has been rapid and impactful. This review relates some of the early history; addresses concerns after two decades of development in the twenty-first century; and discusses how advanced technologies in both materials science and biology will address concerns, advance materials used at the biointerface, and improve outcomes for patients.

Chasing the Paradigm: Clinical Translation of 25 Years of Tissue Engineering.

IMPACT STATEMENT: In this Perspective, we discuss the impact of the past 25 years of tissue engineering on the development of clinical therapies. Based on their success and other significant research accomplishments, platforms of innovation were identified. Their discoveries will enable tissue engineering inspired therapies to meet the requirements necessary for large-scale manufacturing and Food and Drug Administration (FDA) approval for a diverse range of indications.

The history of microsurgery.

Microsurgery is a term used to describe the surgical techniques that require an operating microscope and the necessary specialized instrumentation, the three "Ms" of Microsurgery (microscope, microinstruments and microsutures). Over the years, the crucial factor that transformed the notion of microsurgery itself was the anastomosis of successively smaller blood vessels and nerves that have allowed transfer of tissue from one part of the body to another and re-attachment of severed parts. Currently, with obtained experience, microsurgical techniques are used by several surgical specialties such as general surgery, ophthalmology, orthopaedics, gynecology, otolaryngology, neurosurgery, oral and maxillofacial surgery, plastic surgery and more. This article highlights the most important innovations and milestones in the history of microsurgery through the ages that allowed the inauguration and establishment of microsurgical techniques in the field of surgery.

Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age.

Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g., fluid shear, stretch, compression). A major challenge in tissue engineering for infectious disease research is recreating this dynamic 3-D microenvironment (biological, chemical, and physical/mechanical) to more accurately model the initiation and progression of host-pathogen interactions in the laboratory. Here we review selected 3-D models of human intestinal mucosa, which represent a major portal of entry for infectious pathogens and an important niche for commensal microbiota. We highlight seminal studies that have used these models to interrogate host-pathogen interactions and infectious disease mechanisms, and we present this literature in the appropriate historical context. Models discussed include 3-D organotypic cultures engineered in the rotating wall vessel (RWV) bioreactor, extracellular matrix (ECM)-embedded/organoid models, and organ-on-a-chip (OAC) models. Collectively, these technologies provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies at the intersection of the host, microbe, and their local microenvironments.

Engineering Tissues without the Use of a Synthetic Scaffold: A Twenty-Year History of the Self-Assembly Method.

Twenty years ago, Dr. François A. Auger, the founder of the Laboratory of Experimental Organogenesis (LOEX), introduced the self-assembly technique. This innovative technique relies on the ability of dermal fibroblasts to produce and assemble their own extracellular matrix, differing from all other tissue-engineering techniques that use preformed synthetic scaffolds. Nevertheless, the use of the self-assembly technique was limited for a long time due to its main drawbacks: time and cost. Recent scientific breakthroughs have addressed these limitations. New protocol modifications that aim at increasing the rate of extracellular matrix formation have been proposed to reduce the production costs and laboratory handling time of engineered tissues. Moreover, the introduction of vascularization strategies in vitro permits the formation of capillary-like networks within reconstructed tissues. These optimization strategies enable the large-scale production of inexpensive native-like substitutes using the self-assembly technique. These substitutes can be used to reconstruct three-dimensional models free of exogenous materials for clinical and fundamental applications.

Birth of Airway Surgery and Evolution over the Past Fifty Years.

Significant developments in airway surgery occurred following the introduction of mechanical ventilators and intubation with cuffed endotracheal tubes during the poliomyelitis epidemic of the 1950s. The resulting plethora of postintubation injuries provided extensive experience with resection and reconstruction of stenotic tracheal lesions. In the early 1960s, it was thought that no more 2 cm of trachea could be removed. By the late 1960s, this was challenged owing to better knowledge of airway anatomy and blood supply, tension-releasing maneuvers, and improved anesthetic techniques. Currently, about half of the tracheal length can be safely removed and continuity restored by primary anastomosis.

Tissue-Engineered Heart Valves: A Call for Mechanistic Studies.

Heart valve disease carries a substantial risk of morbidity and mortality. Outcomes are significantly improved by valve replacement, but currently available mechanical and biological replacement valves are associated with complications of their own. Mechanical valves have a high rate of thromboembolism and require lifelong anticoagulation. Biological prosthetic valves have a much shorter lifespan, and they are prone to tearing and degradation. Both types of valves lack the capacity for growth, making them particularly problematic in pediatric patients. Tissue engineering has the potential to overcome these challenges by creating a neovalve composed of native tissue that is capable of growth and remodeling. The first tissue-engineered heart valve (TEHV) was created more than 20 years ago in an ovine model, and the technology has been advanced to clinical trials in the intervening decades. Some TEHVs have had clinical success, whereas others have failed, with structural degeneration resulting in patient deaths. The etiologies of these complications are poorly understood because much of the research in this field has been performed in large animals and humans, and, therefore, there are few studies of the mechanisms of neotissue formation. This review examines the need for a TEHV to treat pediatric patients with valve disease, the history of TEHVs, and a future that would benefit from extension of the reverse translational trend in this field to include small animal studies.

Bone transplantation and tissue engineering, part IV. Mesenchymal stem cells: history in orthopedic surgery from Cohnheim and Goujon to the Nobel Prize of Yamanaka.

In 1867 the German pathologist Cohnheim hypothesized that non-hematopoietic, bone marrow-derived cells could migrate through the blood stream to distant sites of injury and participate in tissue regeneration. In 1868, the French physiologist Goujon studied the osteogenic potential of bone marrow on rabbits. Friedenstein demonstrated the existence of a nonhematopoietic stem cell within bone marrow more than a hundred years later. Since this discovery, the research on mesenchymal stem cell (MSC) has explored their therapeutic potential. The prevalent view during the second century was that mature cells were permanently locked into the differentiated state and could not return to a fully immature, pluripotent stem-cell state. Recently, Japanese scientist (first orthopaedist) Shinya Yamanaka proved that introduction of a small set of transcription factors into a differentiated cell was sufficient to revert the cell to a pluripotent state. Yamanaka shared the Nobel Prize in Physiology or Medicine and opened a new door for potential applications of MSCs. This manuscript describes the concept of MSCs from the period when it was relegated to the imagination to the beginning of the twenty-first century and their application in orthopaedic surgery.

Bone transplantation and tissue engineering, part III: allografts, bone grafting and bone banking in the twentieth century.

During the 20th century, allograft implantation waned in popularity as a clinical activity. Reports appeared in the literature describing several small series of patients in whom bone was obtained from amputation specimens or recently deceased individuals. The concept of bone banking became a reality during and after World War II when the National Naval Tissue Bank was established in Bethesda and a number of small banks sprang up in hospitals throughout the world. Small fragments, either of cortical or medullary bone, from these banks were used heterotopically to augment spinal fusions, to implant into cyst cavities, or to serve as a scaffolding for repair of non- or delayed union of fractures of the long bones.

Cardiovascular tissue engineering: where we come from and where are we now?

Abstract Tissue engineering was introduced by Vacanti and Langer in the 80's, exploring the potential of this new technology starting with the well-known "human ear on the mouse back". The goal is to create a substitute which supplies an individual therapy for patients with regeneration, remodeling and growth potential. The growth potential of these subjects is of special interest in congenital cardiac surgery, avoiding repeated interventions and surgery. Initial applications of tissue engineered created substitutes were relatively simple cardiovascular grafts seeded initially by end-differentiated autologous endothelial cells. Important data were collected from these initial clinical autologous endothelial cell seeded grafts in peripheral and coronary vessel disease. After these initial successfully implantation bone marrow cell were used to seed patches and pulmonary conduits were implanted in patients. Driven by the positive results of tissue engineered material implanted under low pressure circumstances, first tissue engineered patches were implanted in the systemic circulation followed by the implantation of tissue engineered aortic heart valves. Tissue engineering is an extreme dynamic technology with continuously modifications and improvements to optimize clinical products. New technologies are unified and so this has also be done with tissue engineering and new application features, so called transcatheter valve intervention. First studies are initiated to apply tissue engineered heart valves with this new transcatheter delivery system less invasive. Simultaneously studies have been started on tissue engineering of so-called whole organs since organ transplantation is restricted due to donor shortage and tissue engineering could overcome this problem. Initial studies of whole heart engineering in the rat model are promising and larger size models are initiated.

Bone transplantation and tissue engineering. Part II: bone graft and osteogenesis in the seventeenth, eighteenth and nineteenth centuries (Duhamel, Haller, Ollier and MacEwen).

In the 18th century, the fate of allografts and their role in bone formation became of interest to many orthopaedic surgeons. A controversy over the science of osteogenesis, the formation of bone, had emerged following the opposing views of Duhamel and von Haller. Duhamel noted that the periosteum had a deep osteogenic layer, which he termed the "cambium layer". However, von Haller claimed the opposite: the periosteum was not osteogenic. In the 19th century, Ollier performed comprehensive studies on the periosteum. Ollier's experiments were published in two volumes entitled "Traite Experimental et clinique de la regeneration des os" in 1867. His conclusion was that transplanted periosteum and bone survived and could become osteogenic under proper conditions. The controversy was furthered by MacEwen who believed, contrary to Duhamel and Ollier, that the periosteum had no osteogenetic power and was purely a limiting membrane giving direction to bone growth but taking no active part in it. This manuscript describes this period of controversies about the osteogenesis of the transplanted bone, marrow and periosteum that would eventually die or not and be replaced by surrounding tissue or be active for osteogenesis. Whether bone grafts are a form of passive scaffolding or active in osteogenesis was the main question about auto and allografts in the 18th and 19th centuries. In response to this challenge, many papers were written to defend each side of the argument.

On the genealogy of tissue engineering and regenerative medicine.

In this article, we identify and discuss a timeline of historical events and scientific breakthroughs that shaped the principles of tissue engineering and regenerative medicine (TERM). We explore the origins of TERM concepts in myths, their application in the ancient era, their resurgence during Enlightenment, and, finally, their systematic codification into an emerging scientific and technological framework in recent past. The development of computational/mathematical approaches in TERM is also briefly discussed.