Tissue Engineering For Degenerative Intervertebral Discs

Low back pain is a common disorder in the clinical treatment of the Department of Orthopedics. Lumbar intervertebral disc degeneration is a main reason for the chronic pain and the process is difficult to reverse. Traditional treatment methods include conservative treatment and surgical treatment. Although the clinical symptoms caused by intervertebral disc degeneration can be alleviated to a certain extent, these treatment methods do not solve the fundamental issues and they also produce corresponding complications. The rise of tissue engineering technology and its applications in different fields have brought new ideas for the treatment of intervertebral disc degeneration. This book discusses the fundamentals as well as more recent developments in stem cell therapy and tissue engineering technology and offers an alternative for treating degeneration of intervertebral discs.

Disorders related to the intervertebral disc (IVD) are common causes of morbidity and of severe life quality deterioration. IVD degeneration, although in many cases asymptomatic, is often the origin of painful neck and back diseases. In Western societies IVD related pain and disability account for enormous health care costs as a result of work absenteeism and thus lost production, disability benefits, medical and insurance expenses. Although only a small percentage of patients with disc disorders finally will undergo surgery, spinal surgery has been one of the fastest growing disciplines in the musculoskeletal field in recent years. Nevertheless, current treatment options are still a matter of controversial discussion. In particular, they hardly can restore normal spine biomechanics and prevent degeneration of adjacent tissues. While degeneration affects all areas of the IVD, the most constant and noticeable changes occur in the gel-like central part, the nucleus pulposus (NP). Recent emphasis has therefore been put in biological ways to regenerate the NP; however, there are a number of obstacles to overcome, considering the exceptional biological and biomechanical environment of this tissue. Different biological approaches such as molecular, gene, and cell based therapies have been investigated and have shown promising results in both in vitro and in vivo studies. Nonetheless, considerable hurdles still exist in their application for IVD regeneration in human patients. The choice of the cells and the choice of the cell carrier suitable for implantation pose major challenges for research and development activities. This lecture recapitulates the basics of IVD structure, function, and degeneration mechanisms. The first part reviews the recent progress in the field of disc and stem cell based regenerative approaches. In the second part, most appropriate biomaterials that have been evaluated as cell or molecule carrier to cope with degenerative disc disease are outlined. The potential and limitations of cell- and biomaterial-based treatment strategies and perspectives for future clinical applications are discussed. Table of Contents: Cell Therapy for Nucleus Pulposus Regeneration / Recent Advances in Biomaterial Based Tissue Engineering for Intervertebral Disc Regeneration

Disorders related to the intervertebral disc (IVD) are common causes of morbidity and of severe life quality deterioration. IVD degeneration, although in many cases asymptomatic, is often the origin of painful neck and back diseases. In Western societies IVD related pain and disability account for enormous health care costs as a result of work absenteeism and thus lost production, disability benefits, medical and insurance expenses. Although only a small percentage of patients with disc disorders finally will undergo surgery, spinal surgery has been one of the fastest growing disciplines in the musculoskeletal field in recent years. Nevertheless, current treatment options are still a matter of controversial discussion. In particular, they hardly can restore normal spine biomechanics and prevent degeneration of adjacent tissues. While degeneration affects all areas of the IVD, the most constant and noticeable changes occur in the gel-like central part, the nucleus pulposus (NP). Recent emphasis has therefore been put in biological ways to regenerate the NP; however, there are a number of obstacles to overcome, considering the exceptional biological and biomechanical environment of this tissue. Different biological approaches such as molecular, gene, and cell based therapies have been investigated and have shown promising results in both in vitro and in vivo studies. Nonetheless, considerable hurdles still exist in their application for IVD regeneration in human patients. The choice of the cells and the choice of the cell carrier suitable for implantation pose major challenges for research and development activities. This lecture recapitulates the basics of IVD structure, function, and degeneration mechanisms. The first part reviews the recent progress in the field of disc and stem cell based regenerative approaches. In the second part, most appropriate biomaterials that have been evaluated as cell or molecule carrier to cope with degenerative disc disease are outlined. The potential and limitations of cell- and biomaterial-based treatment strategies and perspectives for future clinical applications are discussed. Table of Contents: Cell Therapy for Nucleus Pulposus Regeneration / Recent Advances in Biomaterial Based Tissue Engineering for Intervertebral Disc Regeneration

Degenerative disc disease (DDD) is implicated as one of the primary causes of lower back pain (LBP), the leading cause of disability worldwide. This degeneration is characterized by irreversible detrimental changes to the structure of the intervertebral disc (IVD) which then severely impairs its mechanical function in the spine. The gel-like nucleus pulposus (NP) at its core loses its ability to hydrate while damage propagates through the surrounding annulus fibrosus (AF) in the form of tears and lesions, rendering it unable to resist elastic deformation. Current surgical interventions treat the painful symptoms of the disease rather than the underlying causes, providing only a temporary solution. Tissue-engineered (TE) repair strategies have been proposed for the last two decades as a means of preventing disease advancement in the long term, aiming to restore the native disc's structure as well as repair damage to the cell population. While promising, recapitulating the disc's complex fibrous architecture and mechanical behavior represents an enduring challenge in the field, particularly in attempts to scale up to larger animal models for clinical translation.This thesis sought to augment engineered constructs in vitro by investigating the interplay between matrix composition and mechanical behavior, as well as provide mechanical support to constructs for in vivo delivery. In particular, it describes how the manipulation of fiber formation through media glucose content in vitro plays a critical role in governing matrix structure and mechanical integrity (Chapter 1); how these same mechanisms function in a diseased state in vivo to influence the developing disc (Chapter 2); and how providing a supplemental cage structure to immature TE-IVDs can prevent initial displacement and collapse following implantation to eventually ensure successful tissue integration. Collectively, the work presented here offers crucial insight into how to continue the advancement of biologically based TDR strategies towards use in the clinic.

The intervertebral disc is a complex structure that separates opposing vertebrae, permits a wide range of motion, and accommodates high biomechanical forces. Disc degeneration leads to a loss of function and is often associated with excruciating pain. Written by leading scientists and clinicians, the first part of the book provides a review of the basic biology of the disc in health and disease. The second part considers strategies to mitigate the effects of disc degeneration and discusses the possibility of engineering replacement tissues. The final section is devoted to approaches to model normal development and elucidate the pathogenesis of degenerative disc disease using animal, organ and cell culture techniques. The book bridges the gap between the basic and clinical sciences; the target audience includes basic scientists, orthopaedists and neurologists, while at the same time appealing to the needs of graduate students, medical students, interns and fellows.

Mesenchymal Stem Cells: Isolation, Characterization, and Applications thoroughly presents the isolation, characterization, and some applications of mesenchymal stem cells in the clinic. The book has two parts: "Isolation and Characterization" and "Clinical Perspectives and Applications." In Part I, the subsequent chapters introduce some techniques in isolation, characterization, and purification of mesenchymal stem cells in different tissues. In Part II, some applications of mesenchymal stem cells in the popular diseases, which include cartilage regeneration, spinal cord injury, and osteoarthritis, are discussed. This book provides a succinct yet comprehensive overview of mesenchymal stem cells for advanced students, graduate students, and researchers.

Top Experts Share Clinical Insights on Biological Interventions for Spine-Related Disease Although there have been significant advancements in minimally invasive spinal surgery techniques in the last few decades, optimal outcomes for chronic low back pain remain elusive. A number of promising clinical trials have been conducted using tissue engineering and biological interventions for disc degeneration. Written by renowned innovators, this is the first book that covers implementation of these groundbreaking approaches for disc disease. The text begins with key fundamentals including anatomy and physiology, pathophysiology, imaging and biomechanics to delineate healthy versus diseased spine. Subsequent sections discuss treatment strategies, research findings, and future developments. Throughout each chapter, renowned spine surgeons and scientists share clinical pearls gleaned from hands-on experience. Key Highlights The current state of the art in biological and tissue engineering procedures for spinal disorders Treatment methodologies including nucleus replacement and repair, annulus fibrosus repair, total disc transplantation, and mechanical total disc replacement Innovative treatment strategies for disc regeneration, such as genes and proteins Growth factors including platelet-rich plasma (PRP), which has shown promise for the stimulation and acceleration of bone and soft tissue healing Cell-based therapy for spinal disc regeneration and repair including the use of stem cells and chondrocytes In-depth discussion of research including animal versus human model, in-vitro, and a summary of biologic clinical trials This is a must-have resource for trainee and practicing orthopaedic surgeons and neurosurgeons who treat patients for spine-related conditions. It is essential reading for all clinicians who have an interest in cutting-edge tissue engineering and biological treatment interventions.

Intervertebral disc degeneration is one of the major causes of lower back pain for which the common therapeutic interventions are not efficient. A search for alternative therapies for lower back pain and intervertebral disc degeneration includes cell-based therapies. Unfortunately, intervertebral disc degeneration is avascular and thus a hostile environment for cell survival. Furthermore, cellular characterization in intervertebral disc degeneration, and particularly in the nucleus pulposus, is controversial, mainly due to lack of specific markers and species variability. This book adds to the knowledge on cellular and molecular therapies for intervertebral disc degeneration and associated lower back pain. Key Selling Features: Describes the ontogeny and phenotype of intervertebral disc cells Reviews the role that inflammation plays in disco-genic pain Highlights the types of cells that might be used as sources for treating degenerating intervertebral discs Summarizes current alternative therapies Explores methods for cell delivery into degenerated intervertebral discs