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.

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.

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.

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.

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.

Biomaterials and biotechnology: from the discovery of the first angiogenesis inhibitors to the development of controlled drug delivery systems and the foundation of tissue engineering.

This paper describes the discovery of the first inhibitors of angiogenesis; the discoveries that led to the development of the first biocompatible controlled release systems for macromolecules, and findings that helped to create the field of tissue engineering. In addition, new paradigms for creating biomaterials, early work on nanotechnology in medicine and intelligent drug delivery systems are discussed.

Vascularized composite allotransplantation and tissue engineering.

For many living with the devastating aftermath of disfiguring facial injuries, extremity amputations, and other composite tissues defects, conventional reconstruction offers limited relief. Full restoration of the face or extremities with anatomic equivalents recently became possible with decades of advancements in transplantation and regenerative medicine. Vascularized composite allotransplantation (VCA) is the transfer of anatomic equivalents from immunologically and aesthetically compatible donors to recipients with severe defects. The transplanted tissues are "composite" because they include multiple types essential for function, for example, skin, muscle, nerves, and blood vessels. More than 100 patients worldwide have benefited from VCA, the majority receiving hand or face transplants. Despite its demonstrated results, the clinical practice of VCA is limited by center experience, public awareness, donor shortage, and the risks of lifelong immune suppression. Tissue engineering (TE) is the generation of customized tissues in the laboratory using cells, biomaterials and bioreactors. Tissue engineering may eventually supersede VCA in the clinic, because it bypasses donor shortage and immune suppression challenges. Billions of dollars have been invested in TE research and development, which are expected to result in a myriad of clinical products within the mid- to long-term. First, tissue engineers must address challenges such as vascularization of engineered tissues and maintenance of phenotype in culture. If these hurdles can be overcome, it is to be hoped that the lessons learned through decades of research in both VCA and TE will act synergistically to generate off-the-shelf composite tissues that can thrive after implantation and in the absence of immune suppression.

Trends in tissue engineering for blood vessels.

Over the years, cardiovascular diseases continue to increase and affect not only human health but also the economic stability worldwide. The advancement in tissue engineering is contributing a lot in dealing with this immediate need of alleviating human health. Blood vessel diseases are considered as major cardiovascular health problems. Although blood vessel transplantation is the most convenient treatment, it has been delimited due to scarcity of donors and the patient's conditions. However, tissue-engineered blood vessels are promising alternatives as mode of treatment for blood vessel defects. The purpose of this paper is to show the importance of the advancement on biofabrication technology for treatment of soft tissue defects particularly for vascular tissues. This will also provide an overview and update on the current status of tissue reconstruction especially from autologous stem cells, scaffolds, and scaffold-free cellular transplantable constructs. The discussion of this paper will be focused on the historical view of cardiovascular tissue engineering and stem cell biology. The representative studies featured in this paper are limited within the last decade in order to trace the trend and evolution of techniques for blood vessel tissue engineering.

The development and translation of the tissue-engineered vascular graft.

This lecture will define the classic tissue engineering paradigm, describe cell trafficking with regard to neotissue formation, and explain the role of the host in neotissue formation.

Tissue engineering and regenerative medicine: from first principles to state of the art.

This lecture updates pediatric surgeons on the state of the science of tissue engineering and regenerative medicine.