Cellular therapy aims to replace damaged resident cells by restoring cellular and molecular environments suitable for tissue repair and regeneration. Among several candidates, mesenchymal stem/stromal cells (MSCs) represent a critical component of stromal niches known to be involved in tissue homeostasis. In vitro, MSCs appear as fibroblast-like plastic adherent cells regardless of the tissue source. The therapeutic value of MSCs is being explored in several conditions, including immunological, inflammatory and degenerative diseases, as well as cancer. An improved understanding of their origin and function would facilitate their clinical use. The stemness of MSCs is still debated and requires further study. Several terms have been used to designate MSCs, although consensual nomenclature has yet to be determined. The presence of distinct markers may facilitate the identification and isolation of specific subpopulations of MSCs. Regarding their therapeutic properties, the mechanisms underlying their immune and trophic effects imply the secretion of various mediators rather than direct cellular contact. These mediators can be packaged in extracellular vesicles, thus paving the way to exploit therapeutic cell-free products derived from MSCs. Of importance, the function of MSCs and their secretome are significantly sensitive to their environment. Several features, such as culture conditions, delivery method, therapeutic dose and the immunobiology of MSCs, may influence their clinical outcomes. In this review, we will summarize recent findings related to MSC properties. We will also discuss the main preclinical and clinical challenges that may influence the therapeutic value of MSCs and discuss some optimization strategies.

/pdf/therapeutic-mesenchymal-stem-stromal-cells-value-challenges-1myqbwhp.pdf

Therapeutic Mesenchymal Stem/Stromal Cells: Value, Challenges and Optimization

Musculoskeletal diseases continue to rise on a global scale, causing significant socioeconomic impact and decreased quality of life. The most common disorders affecting musculoskeletal structures are osteoarthritis and tendinopathies, complicated orthopedic conditions responsible for major pain and debilitation. Intra-articular hyaluronic acid (HA) has been a safe, effective, and minimally invasive therapeutic tool for treating these diseases. Several studies from bedside to clinical practice reveal the multiple benefits of HA such as lubrication, anti-inflammation, and stimulation of cellular activity associated with proliferation, differentiation, migration, and secretion of additional molecules. Collectively, these effects have demonstrated positive outcomes that assist in the regeneration of chondral and tendinous tissues which are otherwise destroyed by the predominant catabolic and inflammatory conditions seen in tissue injury. The literature describes the physicochemical, mechanical, and biological properties of HA, their commercial product types, and clinical applications individually, while their interfaces are seldom reported. Our review addresses the frontiers of basic sciences, products, and clinical approaches. It provides physicians with a better understanding of the boundaries between the processes that lead to diseases, the molecular mechanisms that contribute to tissue repair, and the benefits of the HA types for a conscientious choice. In addition, it points out the current needs for the treatments.

/pdf/intra-articular-hyaluronic-acid-in-osteoarthritis-and-20eye9op.pdf

Intra-Articular Hyaluronic Acid in Osteoarthritis and Tendinopathies: Molecular and Clinical Approaches

The physiologic process of blood clot formation is well understood and occurs naturally in the setting of tissue injury to achieve hemostasis and begin the process of wound healing. While the investigation of blood clots as a biomaterial is still in the early stages, there has been some research with similar biomaterials made of the components of blood clots that support the innovative idea of using an autologous blood clot as a scaffold or delivery method for therapeutic agents. Here, we review the physiology of blood clots in wound healing and how using blood clots as a biomaterial and delivery system can potentially promote wound healing, provide targeted therapeutic agent delivery and use it as an innovative tool in regenerative medicine.

The advances of blood clots used as biomaterials in regenerative medicine.

PURPOSE OF REVIEW A wide array of joint-preserving surgical techniques exists in the management of acetabular chondral defects (ACDs). The purpose of this review is to summarize the clinical outcomes of the recent biologics used to treat ACDs during hip arthroscopy. RECENT FINDINGS Increasing evidence is available for different biological solutions used in the hip. Studies have shown promising outcomes with minimal complications when using biologics as augmentation to microfracture (MF), including different scaffolds or stem cells, or to enhance autologous chondrocyte implantation (ACI). However, data so far is scarce, and more trials and longer follow-ups are needed to better delineate the appropriate indications and benefits for each technique. Presently, the level of evidence is low, but in general, biologics appear safe and trend toward beneficial compared to standard surgical techniques. Augmented MF is recommended for small to medium ACDs, and matrix-assisted ACI or three-dimensional ACI is recommended for medium to large defects.

https://link.springer.com/content/pdf/10.1007/s12178-021-09721-8.pdf

Biological Augments for Acetabular Chondral Defects in Hip Arthroscopy-A Scoping Review of the Current Clinical Evidence.

Femoroacetabular impingement (FAI) is one of the most common causes of labral and early cartilage damage in the nondysplastic hip. FAI is increasingly recognized as a cause for hip and groin pain in the young, active patient, and the surgical treatment of FAI with hip arthroscopy has risen exponentially. Although our understanding of FAI and the progression to degenerative osteoarthritis of the hip has historically been considered a mechanical "wear-and-tear" disease of an imperfectly shaped, aspherical, femoral head within a deep or overcovering acetabulum leading to cartilage injury, our understanding of the intrinsic pathophysiologic mechanisms underlying the development of FAI and joint degeneration of the hip remains poor. For example, many patients with FAI morphology may never develop hip pain or osteoarthritis; there remains more to discover regarding the pathophysiology of arthritis in the setting of FAI. Recent work has begun to identify a strong inflammatory and immunologic component to the FAI disease process that affects the hip synovium, labrum, and cartilage and may be detectable from peripheral clinical samples (blood and urine). This review highlights our current understanding of the inflammatory and immunologic contributions to FAI and potential therapeutic strategies to supplement and augment the surgical management of FAI. 

Inflammatory and Immunologic Contributions in Femoroacetabular Impingement Syndrome

Orthobiologics are biological materials that are intended for the regeneration or healing of bone, cartilage and soft tissues. In this review we discuss the use of orthobiologics for hip disorders providing an update. The orthobiologics included in this article are hyaluronic acid, platelet rich plasma, bone marrow, adipose tissue and expanded mesenchymal stem cells. We explain the concepts and definitions of each orthobiological product, and the literature regarding its use in the hip joint. The paucity of guidelines for the production and characterization of the biological products leads to uneven results across the literature. Each biologic therapy has indications and benefits; however, noteworthy are the characterization of the orthobiologics, the application method and outcome analysis for further improvement of each technique.

Orthobiologics in the treatment of hip disorders

This chapter addresses several aspects of spine disorders and their implications for pain, functional impairment, and their problems and treatments.

Paulo David Fortis Gusmão

Papers

Orthobiologics in the treatment of hip disorders

The Role of Biological Treatments in Spine Disorders