Inflammation And Tendon Healing

Tendons heal through three different overlapping phases; the inflammatory, proliferative and remodeling phase. Many studies have investigated what factors influence healing of tendons. However, little was known about inflammation and the immune cells present during Achilles tendon healing by the time this thesis started. We developed a flow cytometry method for our rat model of tendon healing, which enabled us to study different leukocyte subpopulations during Achilles tendon healing. The general aim of this thesis was to understand more about inflammation and the immune cell populations present during tendon healing and how the immune cell composition changes during normal tendon healing. Moreover, we investigated how different factors that are known to influence tendon healing affected the composition of the immune cell population. First, we described the immune cells during the time course of tendon healing focusing on different subpopulations of macrophages and T cells. Then, we studied how these cells were influenced by reduced mechanical loading. Mechanical loading prolonged the presence of M1 macrophages and delayed the switch to regulatory T cells and M2 macrophages compared to reduced mechanical loading. Next, the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the leukocyte composition revealed that, even though NSAIDs influence the mechanical properties of healing tendon, this effect was not mediated via changes in the leukocyte sub-populations during early and mid-time tendon healing. Further, the effect of corticosteroids during the inflammatory and remodeling phases of tendon healing was an improved healing of tendons and a reduction of CD8a T cells when corticosteroid was administered after the inflammatory phase. Lastly, we investigated if impairment of tendon healing by NSAIDs was related to mechanotransduction or microdamage during mechanical loading and showed that NSAIDs impair tendon healing by reducing the response to microdamage. In conclusion, these studies show that inflammation plays an important role during Achilles tendon healing, and factors that influence healing can also alter the presence or polarization of immune cell populations.

Mechanical loading and the inflammatory response during tendon healing might be important for the healing process. Mechanical loading can improve the healing tendon but the mechanism is not fully understood. The aim of this thesis was to further clarify the effect of mechanical loading on tendon healing and how mechanical loading affects the inflammatory response during the healing process. We used a rat Achilles tendon model to study healing. The rats were exposed to different degrees of loading by unloading methods such as paralysis of the calf muscles with Botox, tail suspension, and an orthosis (a boot). Full loading was achieved by free cage activity or treadmill walking. Microdamage in tendons, unloaded with Botox, was also investigated by needling. The healing tendons were evaluated in a materials testing machine (to analyze the mechanical properties), by gene expression analysis (microarray and PCR), or histology. Our results show that moderate loading (unloading with Botox) improves the mechanical properties of healing tendons compared to minimal loading (unloading with Botox in combination with tail suspension or a boot), especially the material properties. In accordance to these findings, expression of extracellular matrix genes were also increased by moderate compared to minimal loading. Full loading improved all mechanical properties and the expression of extracellular matrix genes was further increased compared to moderate loading. However, structural properties, such as the strength and the size of the healing tendon, were more affected by full loading. Full loading also affected the expression of inflammation-related genes during the early healing phase, 3 and 5 days after tendon injury, and increased the number of immune cells in the healing tendon tissue. Also microdamage of the healing tendon (detected by blood leakage) was increased by full loading compared to moderate loading during the early healing phase. Induced microdamage by repeated needling in the healing tendon tissue increased the structural properties of the healing tendon. The gene expression after needling was similar to the gene expression after full loading. The improvement of mechanical properties by loading in healing tendons was decreased by an anti-inflammatory drug called parecoxib, which decreases the production of prostaglandins by inhibiting COX-2 activity. The effect of parecoxib was reduced when loading was reduced but we could not confirm that the effect of parecoxib was related to the degree of loading. However, parecoxib abolished the stimulatory effect of microdamage. In conclusion, these studies show that moderate loading improves the quality of the healing tendon whereas full loading also increases the quantity of the healing tendon tissue. Full loading creates microdamage and increases inflammation during the early healing phase. The strong effect of full loading on the structural properties might be due to microdamage. Indeed, the anti-inflammatory drug parecoxib seems to impair mechanical stimulation of healing tendons by reducing the response to microdamage.

In 25 years of practicing structural/osteopathic manual therapy the author has done considerable work with seriously damaged tendons and ligaments, and has achieved results that conventional medicine would rate as improbable. Over time, he has developed a therapeutic model for treating these injuries so that individuals with chronic conditions -- who have exhausted the standard physiotherapy options and are facing surgery -- can have a viable option for recovery. His techniques, based on basic principles of structural healthcare, emphasize the importance of precise anatomical focus and the capacity to work with subtle changes of structure. Of essential importance is combining detailed specific treatment of the small fibers and tissues of the local injury area with an overall approach to improving larger body patterns and tensions. Logically, the responsiveness and self-corrective capacity of body tissues when given proper conditions is also an important factor. The primary techniques used are the osteopathic methods of strain-counterstrain, cranial and visceral osteopathy, and fascial release, as well as body-mind centering, zero balancing, and acupressure. His clinical model, which represents a new approach to serious, chronic tendon and ligament injuries, is based on these techniques, their combinations and specific usage, and the skills and aptitudes necessary for applying these techniques, including certain perceptual skills and a thorough knowledge of anatomy and kinesiology. Weintraub's descriptions are vital, interesting, alive, absorbing, even dramatic. He discusses at great length the nature of the tendons and ligaments, describes his manual therapy model -- comparing it with conventional medical procedures -- and covers processes and tissue changes in tendon/ligament healing as related to manual therapy. Case studies, self-help strategies, and thoughtful words on clinical efficacy and future directions in the field make for a thorough and well-rounded presentation. (Product Description).

Tendon Regeneration: Understanding Tissue Physiology and Development to Engineer Functional Substitutes is the first book to highlight the multi-disciplinary nature of this specialized field and the importance of collaboration between medical and engineering laboratories in the development of tissue-oriented products for tissue engineering and regenerative medicine (TERM) strategies. Beginning with a foundation in developmental biology, the book explores physiology, pathology, and surgical reconstruction, providing guidance on biological approaches that enhances tendon regeneration practices. Contributions from scientists, clinicians, and engineers who are the leading figures in their respective fields present recent findings in tendon stem cells, cell therapies, and scaffold treatments, as well as examples of pre-clinical models for translational therapies and a view of the future of the field. Provides an overview of tendon biology, disease, and tissue engineering approaches Presents modern, alternative approaches to developing functional tissue solutions discussed Includes valuable information for those interested in tissue engineering, tissue regeneration, tissue physiology, and regenerative medicine Explores physiology, pathology, and surgical reconstruction, building a natural progression that enhances tendon regeneration practices Covers recent findings in tendon stem cells, cell therapies, and scaffold treatments, as well as examples of pre-clinical models for translational therapies and a view of the future of the field

This concise volume in the Encyclopaedia of Sports Medicine series, published under the auspices of the International Olympic Committee, provides a dependable source of current knowledge available on tendinopathy and covers both the basic science and clinical aspects of the subject. Despite its high incidence, the precise etiopathogenesis and effective treatment of tendinopathy remain elusive. Tendinopathy in Athletes draws on the expertise of an international and prolific collection of contributors, both clinicians and scientists, who provide new insights into this specialized area. This book: provides a comprehensive resource for both clinicians and researchers with information organized logically, with an easy-to-follow progression from the basic scientific findings to clinical applications discusses the full range of treatment modalities, including new molecular and biological approaches, plus surgical and alternative approaches to tendinopath contains “What We Need to Know” sections that suggest future areas of research for young investigators. As tendinopathy remains one of the most common injuries encountered, both in sports and at the workplace, this essential volume is sure to be a source of frequent consultation.

This book will be of considerable interest to students, practitioners (Doctors, Physiotherapists, and other health care professionals), and researchers who deal with the complex structure of tendons and the need to effectively address tendon disorders. The book is divided into three sections: (1) Basic Biology and Biochemical Markers; (2) Metabolic Disorders; and (3) Novel Therapies. The first section, devoted to the basic biology of tendons, is aimed at those individuals who want to gain basic information on tendons and the subsection on biochemical markers is chiefly aimed at researchers who are developing new studies within this field. The section on metabolic disorders is mainly directed at practitioners who desire to know how metabolic disorders can affect tendons in order to optimize treatment for their patients. Finally, the section on novel therapies is focused on some new treatment options within this field, and discussions regarding how management of tendon disorders needs to incorporate perspectives on current understanding of tendon metabolism.

This reference work presents the origins of cells for tissue engineering and regeneration, including primary cells, tissue-specific stem cells, pluripotent stem cells and trans-differentiated or reprogrammed cells. There is particular emphasis on current understanding of tissue regeneration based on embryology and evolution studies, including mechanisms of amphibian regeneration. The book covers the use of autologous versus allogeneic cell sources, as well as various procedures used for cell isolation and cell pre-conditioning , such as cell sorting, biochemical and biophysical pre-conditioning, transfection and aggregation. It also presents cell modulation using growth factors, molecular factors, epigenetic approaches, changes in biophysical environment, cellular co-culture and other elements of the cellular microenvironment. The pathways of cell delivery are discussed with respect to specific clinical situations, including delivery of ex vivo manipulated cells via local and systemic routes, as well as activation and migration of endogenous reservoirs of reparative cells. The volume concludes with an in-depth discussion of the tracking of cells in vivo and their various regenerative activities inside the body, including differentiation, new tissue formation and actions on other cells by direct cell-to-cell communication and by secretion of biomolecules.

This book introduces the exciting field of orthobiology, which will usher in a new array of therapeutic approaches that stimulate the body’s natural resources to regenerate musculoskeletal tissues damaged by trauma or disease. The book addresses a range of key topics and discusses emerging approaches that promise to offer effective alternatives to traditional treatments for injuries to bone, cartilage, muscles, ligaments, and tendons. It explains in detail how a variety of innovative products, including biomaterials, growth factors, and autogenous cells, together provide the basis for the regeneration of these musculoskeletal structures and how recent scientific progress has created unique opportunities to address pathological situations that until recently have been treated with unsatisfactory results. The authors are experts from across the world who come together to provide a truly global overview. The book is published in collaboration with ISAKOS. It will be invaluable for all with an interest in this area of medicine, which has already attained huge popularity in Orthopaedics and Sports Medicine and has also attracted the attention of the lay public.