Fibroblast growth factor 8b (FGF-8b) enhances myogenesis and inhibits adipogenesis in rotator cuff muscle cell populations in vitro.

Fatty expansion is one of the features of muscle degeneration due to muscle injuries, and its presence interferes with muscle regeneration. Specifically, poor clinical outcomes have been linked to fatty expansion in rotator cuff tears and repairs. Our group recently found that fibroblast growth factor 8b (FGF-8b) inhibits adipogenic differentiation and promotes myofiber formation of mesenchymal stem cells in vitro. This led us to hypothesize that FGF-8b could similarly control the fate of muscle-specific cell populations derived from rotator cuff muscle involved in muscle repair following rotator cuff injury. In this study, we isolate fibro-adipogenic progenitor cells (FAPs) and satellite stem cells (SCs) from rat rotator cuff muscle tissue and analyzed the effects of FGF-8b supplementation. Utilizing a cell plating protocol, we successfully isolate FAPs-rich fibroblasts (FIBs) and SCs-rich muscle progenitor cells (MPCs). Subsequently, we demonstrate that FIB adipogenic differentiation can be inhibited by FGF-8b, while MPC myogenic differentiation can be enhanced by FGF-8b. We further demonstrate that phosphorylated ERK due to FGF-8b leads to the inhibition of adipogenesis in FIBs and SCs maintenance and myofiber formation in MPCs. Together, these findings demonstrate the powerful potential of FGF-8b for rotator cuff repair by altering the fate of muscle undergoing degeneration.

Development of porcine skeletal muscle extracellular matrix-derived hydrogels with improved properties and low immunogenicity.

Hydrogels derived from decellularized extracellular matrices (ECM) of animal origin show immense potential for regenerative applications due to their excellent cytocompatibility and biomimetic properties. Despite these benefits, the impact of decellularization protocols on the properties and immunogenicity of these hydrogels remains relatively unexplored. In this study, porcine skeletal muscle ECM (smECM) underwent decellularization using mechanical disruption (MD) and two commonly employed decellularization detergents, sodium deoxycholate (SDC) or Triton X-100. To mitigate immunogenicity associated with animal-derived ECM, all decellularized tissues were enzymatically treated with α-galactosidase to cleave the primary xenoantigen-the α-Gal antigen. Subsequently, the impact of the different decellularization protocols on the resultant hydrogels was thoroughly investigated. All methods significantly reduced total DNA content in hydrogels. Moreover, α-galactosidase treatment was crucial for cleaving α-Gal antigens, suggesting that conventional decellularization methods alone are insufficient. MD preserved total protein, collagen, sulfated glycosaminoglycan, laminin, fibronectin, and growth factors more efficiently than other protocols. The decellularization method impacted hydrogel gelation kinetics and ultrastructure, as confirmed by turbidimetric and scanning electron microscopy analyses. MD hydrogels demonstrated high cytocompatibility, supporting satellite stem cell recruitment, growth, and differentiation into multinucleated myofibers. In contrast, the SDC and Triton X-100 protocols exhibited cytotoxicity. Comprehensive in vivo immunogenicity assessments in a subcutaneous xenotransplantation model revealed MD hydrogels' biocompatibility and low immunogenicity. These findings highlight the significant influence of the decellularization protocol on hydrogel properties. Our results suggest that combining MD with α-galactosidase treatment is an efficient method for preparing low-immunogenic smECM-derived hydrogels with enhanced properties for skeletal muscle regenerative engineering and clinical applications.

Hyaluronic acid-British anti-Lewisite as a safer chelation therapy for the treatment of arthroplasty-related metallosis.

Cobalt-containing alloys are useful for orthopedic applications due to their low volumetric wear rates, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. Unfortunately, these prosthetics release significant levels of cobalt ions, which was only discovered after their widespread implantation into patients requiring hip replacements. These cobalt ions can result in local toxic effects-including peri-implant toxicity, aseptic loosening, and pseudotumor-as well as systemic toxic effects-including neurological, cardiovascular, and endocrine disorders. Failing metal-on-metal (MoM) implants usually necessitate painful, risky, and costly revision surgeries. To treat metallosis arising from failing MoM implants, a synovial fluid-mimicking chelator was designed to remove these metal ions. Hyaluronic acid (HA), the major chemical component of synovial fluid, was functionalized with British anti-Lewisite (BAL) to create a chelator (BAL-HA). BAL-HA effectively binds cobalt and rescues in vitro cell vitality (up to 370% of cells exposed to IC50 levels of cobalt) and enhances the rate of clearance of cobalt in vivo (t1/2 from 48 h to 6 h). A metallosis model was also created to investigate our therapy. Results demonstrate that BAL-HA chelator system is biocompatible and capable of capturing significant amounts of cobalt ions from the hip joint within 30 min, with no risk of kidney failure. This chelation therapy has the potential to mitigate cobalt toxicity from failing MoM implants through noninvasive injections into the joint.

Regenerative engineering of long bones using the small molecule forskolin.

Bone grafting procedures have become increasingly common in the United States, with approximately 500,000 cases occurring each year at a societal cost exceeding $2.4 billion. Recombinant human bone morphogenetic proteins (rhBMPs) are therapeutic agents that have been widely used by orthopedic surgeons to stimulate bone tissue formation alone and when paired with biomaterials. However, significant limitations such as immunogenicity, high production cost, and ectopic bone growth from these therapies remain. Therefore, efforts have been made to discover and repurpose osteoinductive small-molecule therapeutics to promote bone regeneration. Previously, we have demonstrated that a single-dose treatment with the small-molecule forskolin for just 24 h induces osteogenic differentiation of rabbit bone marrow-derived stem cells in vitro, while mitigating adverse side effects attributed with prolonged small-molecule treatment schemes. In this study, we engineered a composite fibrin-PLGA [poly(lactide-co-glycolide)]-sintered microsphere scaffold for the localized, short-term delivery of the osteoinductive small molecule, forskolin. In vitro characterization studies showed that forskolin released out of the fibrin gel within the first 24 h and retained its bioactivity toward osteogenic differentiation of bone marrow-derived stem cells. The forskolin-loaded fibrin-PLGA scaffold was also able to guide bone formation in a 3-mo rabbit radial critical-sized defect model comparable to recombinant human bone morphogenetic protein-2 (rhBMP-2) treatment, as demonstrated through histological and mechanical evaluation, with minimal systemic off-target side effects. Together, these results demonstrate the successful application of an innovative small-molecule treatment approach within long bone critical-sized defects.

The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering.

Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also may contain factors antagonistic to targeted tissue regeneration. We have therefore engineered a synthetic artificial stem cell (SASC) system which mimics the paracrine effect of the stem cell secretome and provides tailorability of the composition for targeted tissue regeneration. We report the first of many applications of the SASC system we have formulated to treat osteoarthritis (OA). Choosing growth factors important to chondrogenesis and encapsulating respective recombinant proteins in poly (lactic-coglycolic acid) 85:15 (PLGA) we fabricated the SASC system. We compared the antiinflammatory and chondroprotective effects of SASC to that of adipose-derived stem cells (ADSCs) using in vitro interleukin 1B-induced and in vivo collagenase-induced osteoarthritis rodent models. We have designed SASC as an injectable therapy with controlled release of the formulated secretome. In vitro, SASC showed significant antiinflammatory and chondroprotective effects as seen by the up-regulation of SOX9 and reduction of nitric oxide, ADAMTS5, and PRG4 genes compared to ADSCs. In vivo, treatment with SASC and ADSCs significantly attenuated cartilage degeneration and improved the biomechanical properties of the articular cartilage in comparison to OA control. This SASC system demonstrates the feasibility of developing a completely synthetic, tailorable stem cell secretome which reinforces the possibility of developing a new therapeutic strategy that provides better control over targeted tissue engineering applications.

Muscle degeneration in chronic massive rotator cuff tears of the shoulder: Addressing the real problem using a graphene matrix.

Massive rotator cuff tears (MRCTs) of the shoulder cause disability and pain among the adult population. In chronic injuries, the tendon retraction and subsequently the loss of mechanical load lead to muscle atrophy, fat accumulation, and fibrosis formation over time. The intrinsic repair mechanism of muscle and the successful repair of the torn tendon cannot reverse the muscle degeneration following MRCTs. To address these limitations, we developed an electroconductive matrix by incorporating graphene nanoplatelets (GnPs) into aligned poly(l-lactic acid) (PLLA) nanofibers. This study aimed to understand 1) the effects of GnP matrices on muscle regeneration and inhibition of fat formation in vitro and 2) the ability of GnP matrices to reverse muscle degenerative changes in vivo following an MRCT. The GnP matrix significantly increased myotube formation, which can be attributed to enhanced intracellular calcium ions in myoblasts. Moreover, the GnP matrix suppressed adipogenesis in adipose-derived stem cells. These results supported the clinical effects of the GnP matrix on reducing fat accumulation and muscle atrophy. The histological evaluation showed the potential of the GnP matrix to reverse muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 wk after the chronic MRCTs of the rat shoulder. The pathological evaluation of internal organs confirmed the long-term biocompatibility of the GnP matrix. We found that reversing muscle degenerative changes improved the morphology and tensile properties of the tendon compared with current surgical techniques. The long-term biocompatibility and the ability of the GnP matrix to treat muscle degeneration are promising for the realization of MRCT healing and regeneration.

Injectable amnion hydrogel-mediated delivery of adipose-derived stem cells for osteoarthritis treatment.

Current treatment strategies for osteoarthritis (OA) predominantly address symptoms with limited disease-modifying potential. There is a growing interest in the use of adipose-derived stem cells (ADSCs) for OA treatment and developing biomimetic injectable hydrogels as cell delivery systems. Biomimetic injectable hydrogels can simulate the native tissue microenvironment by providing appropriate biological and chemical cues for tissue regeneration. A biomimetic injectable hydrogel using amnion membrane (AM) was developed which can self-assemble in situ and retain the stem cells at the target site. In the present study, we evaluated the efficacy of intraarticular injections of AM hydrogels with and without ADSCs in reducing inflammation and cartilage degeneration in a collagenase-induced OA rat model. A week after the induction of OA, rats were treated with control (phosphate-buffered saline), ADSCs, AM gel, and AM-ADSCs. Inflammation and cartilage regeneration was evaluated by joint swelling, analysis of serum by cytokine profiling and Raman spectroscopy, gross appearance, and histology. Both AM and ADSC possess antiinflammatory and chondroprotective properties to target the sites of inflammation in an osteoarthritic joint, thereby reducing the inflammation-mediated damage to the articular cartilage. The present study demonstrated the potential of AM hydrogel to foster cartilage tissue regeneration, a comparable regenerative effect of AM hydrogel and ADSCs, and the synergistic antiinflammatory and chondroprotective effects of AM and ADSC to regenerate cartilage tissue in a rat OA model.

Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits.

The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(l-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. This study aims to 1) accelerate the rate of regeneration using the bioengineered ACL matrix by supplementation with bone marrow aspirate concentrate (BMAC) and growth factors (BMP-2, FGF-2, and FGF-8) and 2) increase matrix strength retention. Histological evaluation showed robust tissue regeneration in all groups. The presence of cuboidal cells reminiscent of ACL fibroblasts and chondrocytes surrounded by an extracellular matrix rich in anionic macromolecules was up-regulated in the BMAC group. This was not observed in previous studies and is indicative of enhanced regeneration. Additionally, intraarticular treatment with FGF-2 and FGF-8 was found to suppress joint inflammation. To increase matrix strength retention, we incorporated nondegradable fibers, polyethylene terephthalate (PET), into the PLLA bioengineered ACL matrix to fabricate a "tiger graft." The tiger graft demonstrated the greatest peak loads among the experimental groups and the highest to date in a rabbit model. Moreover, the tiger graft showed superior osteointegration, making it an ideal bioengineered ACL matrix. The results of this study illustrate the beneficial effect bioactive factors and PET incorporation have on ACL regeneration and signal a promising step toward the clinical translation of a functional bioengineered ACL matrix.

Biodegradable Polyphosphazenes for Regenerative Engineering.

Regenerative engineering is a field that seeks to regenerate complex tissues and biological systems, rather than simply restore and repair individual tissues or organs. Since the first introduction of regenerative engineering in 2012, numerous research has been devoted to the development of this field. Biodegradable polymers such as polyphosphazenes in particular have drawn significant interest as regenerative engineering materials for their synthetic flexibility in designing into materials with a wide range of mechanical properties, degradation rates, and chemical functionality. These polyphosphazenes can go through complete hydrolytic degradation and provide harmlessly and pH neutral buffering degradation products such as phosphates and ammonia, which is crucial for reducing inflammation in vivo. Here, we discuss the current accomplishments of polyphosphazene, different methods for synthesizing them, and their applications in tissue regeneration such as bones, nerves, and elastic tissues.

Phosphate graphene as an intrinsically osteoinductive scaffold for stem cell-driven bone regeneration.

Synthetic, resorbable scaffolds for bone regeneration have potential to transform the clinical standard of care. Here, we demonstrate that functional graphenic materials (FGMs) could serve as an osteoinductive scaffold: recruiting native cells to the site of injury and promoting differentiation into bone cells. By invoking a Lewis acid-catalyzed Arbuzov reaction, we are able to functionalize graphene oxide (GO) to produce phosphate graphenes (PGs) with unprecedented control of functional group density, mechanical properties, and counterion identity. In aqueous environments, PGs release inducerons, including Ca2+ and PO43- Calcium phosphate graphene (CaPG) intrinsically induces osteogenesis in vitro and in the presence of bone marrow stromal cells (BMSCs), can induce ectopic bone formation in vivo. Additionally, an FGM can be made by noncovalently loading GO with the growth factor recombinant human bone morphogenetic protein 2 (rhBMP-2), producing a scaffold that induces ectopic bone formation with or without BMSCs. The FGMs reported here are intrinsically inductive scaffolds with significant potential to revolutionize the regeneration of bone.

Selective Unique Signs of Meniscus Tears as Visualized by Magnetic Resonance Imaging.

ABSTRACT: The meniscus is an organized collection of fibrocartilaginous tissue that is located between the femoral condyles and the tibial plateau of the knee which primarily assists with load transmission. The complex composition of articulating soft-tissue structures in the knee causes the menisci to become a common source of injury, especially in the realm of athletic trauma. Magnetic resonance imaging (MRI) has become the imaging modality of choice for evaluating patients with suspected meniscal pathology because of its numerous advantages over plain radiographs. Most forms of meniscal tears have classic MRI findings and are used in correlation with physical examination findings to confirm or rule out a diagnosis. These imaging findings are referred to as signs and have been well studied, and the associated eponyms for each sign are well published throughout the literature. This article will review and describe a unique selection of meniscal pathology as visualized by MRI that is more commonly published in musculoskeletal radiology literature when compared with orthopedics and sports medicine literature.

Biodegradable Piezoelectric Force Sensor.

Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here, we present a strategy for material processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-l-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0-18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices.

Spatial alignment of 3D printed scaffolds modulates genotypic expression in pre-osteoblasts.

3D printing, an advent from rapid prototyping technology is emerging as a suitable solution for various regenerative engineering applications. In this study, blended gelatin-sodium alginate 3D printed scaffolds with different pore geometries were developed by altering the spatiotemporal alignment of even layered struts in the scaffolds. A significant difference in compression modulus and osteogenic expression due to the difference in spatiotemporal printing was demonstrated. Pore geometry was found to be more dominant than the compressive modulus of the scaffold in regulating osteogenic gene expression. A shift in pore geometry by at least 45° was critical for significant increase in osteogenic gene expression in MC3T3-E1 cells.

Generational Biodegradable and Regenerative Polyphosphazene Polymers and their Blends with Poly (lactic-co-glycolic acid).

New fields such as regenerative engineering have driven the design of advanced biomaterials with a wide range of properties. Regenerative engineering is a multidisciplinary approach that integrates the fields of advanced materials science and engineering, stem cell science, physics, developmental biology, and clinical translation for the regeneration of complex tissues. The complexity and demands of this innovative approach have motivated the synthesis of new polymeric materials that can be customized to meet application-specific needs. Polyphosphazene polymers represent this fundamental change and are gaining renewed interest as biomaterials due to their outstanding synthetic flexibility, neutral bioactivity (buffering degradation products), and tunable properties across the range. Polyphosphazenes are a unique class of polymers composed of an inorganic backbone with alternating phosphorus and nitrogen atoms. Each phosphorus atom bears two substituents, with a wide variety of side groups available for property optimization. Polyphosphazenes have been investigated as potential biomaterials for regenerative engineering. Polyphosphazenes for use in regenerative applications have evolved as a class to include different generations of degradable polymers. The first generation of polyphosphazenes for tissue regeneration entailed the use of hydrolytically active side groups such as imidazole, lactate, glycolate, glucosyl, or glyceryl groups. These side groups were selected based on their ability to sensitize the polymer backbone to hydrolysis, which allowed them to break down into non-toxic small molecules that could be metabolized or excreted. The second generation of degradable polyphosphazenes developed consisted of polymers with amino acid ester side groups. When blended with poly (lactic acid-co-glycolic acid) (PLGA), the feasibility of neutralizing acidic degradation products of PLGA was demonstrated. The blends formed were mostly partially miscible. The desire to improve miscibility led to the design of the third generation of degradable polyphosphazenes by incorporating dipeptide side groups which impart significant hydrogen bonding capability to the polymer for the formation of completely miscible polyphosphazene-PLGA blends. Blend system of the dipeptide-based polyphosphazene and PLGA exhibit a unique degradation behavior that allows the formation of interconnected porous structures upon degradation. These inherent pore-forming properties have distinguished degradable polyphosphazenes as a potentially important class of biomaterials for further study. The design considerations and strategies for the different generations of degradable polyphosphazenes and future directions are discussed.

Microsphere-Based Scaffolds in Regenerative Engineering.

Microspheres have long been used in drug delivery applications because of their controlled release capabilities. They have increasingly served as the fundamental building block for fabricating scaffolds for regenerative engineering because of their ability to provide a porous network, offer high-resolution control over spatial organization, and deliver growth factors/drugs and/or nanophase materials. Because they provide physicochemical gradients via spatiotemporal release of bioactive factors and nanophase ceramics, microspheres are a desirable tool for engineering complex tissues and biological interfaces. In this review we describe various methods for microsphere fabrication and sintering, and elucidate how these methods influence both micro- and macroscopic scaffold properties, with a special focus on the nature of sintering. Furthermore, we review key applications of microsphere-based scaffolds in regenerating various tissues. We hope to inspire researchers to join a growing community of investigators using microspheres as tissue engineering scaffolds so that their full potential in regenerative engineering may be realized.

Regenerative Engineering and Bionic Limbs.

Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next two decades.

Adopt-A-Classroom Program: A Potential Platform to Address the Root of Health Disparities in the US.

The underrepresentation of Black doctors is a significant issue in the US that led to the perpetuation of health disparities in the African American community. Racial and ethnic minorities in the US have been shown to have higher rates of chronic diseases, such as hypertension, diabetes, and cardiovascular disease, as well as higher rates of obesity and premature death compared to White people. While Blacks make up more than 13% of the US population, they comprise only 4% of US doctors and less than 7% of medical students. It is believed that this problem requires more deliberate efforts by policymakers and the educational establishment, not only at the undergraduate and medical school level, but earlier in the educational "pipeline"-the K-12 school system. While the medical field is rooted in Science, Technology, Engineering, and Mathematics (STEM), we have launched a new initiative that will provide year-round STEM development activities for K-12 education in Connecticut in Hartford and Waterbury districts, especially among populations with health disparities.

Animal Models of Osteoarthritis: Updated Models and Outcome Measures 2016-2023.

Purpose: Osteoarthritis (OA) is a global musculoskeletal disorder that affects primarily the knee and hip joints without any FDA-approved disease-modifying therapies. Animal models are essential research tools in developing therapies for OA; many animal studies have provided data for the initiation of human clinical trials. Despite this, there is still a need for strategies to recapitulate the human experience using animal models to better develop treatments and understand pathogenesis. Since our last review on animal models of osteoarthritis in 2016, there have been exciting updates in OA research and models. The main purpose of this review is to update the latest animal models and key features of studies in OA research. Method: We used our existing classification method and screened articles in PubMed and bibliographic search for animal OA models between 2016 and 2023. Relevant and high-cited articles were chosen for inclusion in this narrative review. Results: Recent studies were analyzed and classified. We also identified ex vivo models as an area of ongoing research. Each animal model offers its own benefit in the study of OA and there are a full range of outcome measures that can be assessed. Despite the vast number of models, each has its drawbacks that have limited translating approved therapies for human use. Conclusion: Depending on the outcome measures and objective of the study, researchers should pick the best model for their work. There have been several exciting studies since 2016 that have taken advantage of regenerative engineering techniques to develop therapies and better understand OA. Lay Summary: Osteoarthritis (OA) is a chronic debilitating disease without any cure that affects mostly the knee and hip joints and often results in surgical joint replacement. Cartilage protects the joint from mechanical forces and degrades with age or in response to injury. The many contributing causes of OA are still being investigated, and animals are used for preclinical research and to test potential new treatments. A single consensus OA animal model for preclinical studies is non-existent. In this article, we review the many animal models for OA and provide a much-needed update on studies and model development since 2016.

Functions and Effectiveness of Unloader, Patellofemoral, and Knee Sleeve Orthoses: A Review.

Background: Knee orthoses have been extensively used as a nonsurgical approach to improving knee deficiencies. Currently, arthritic knee conditions remain the leading cause of disability, and this number is expected to increase. As the use of knee orthoses varies widely, so has their effectiveness which is still largely debatable. Here, we present the functions and effectiveness of the three most prominent knee orthotic models dedicated to supporting knee osteoarthritis-unloader, patellofemoral, and knee sleeves. Purpose/Research Question: Considering the depth and diversity of the many clinical studies and documented laboratory reports published to date, this literature review was created to educate the clinician, patient, and researcher on common knee orthoses used for the management of arthritic knee conditions. In doing so, we discuss their design, biomechanical effects, and clinical efficacy, as well as broader outcomes, limitations, and recommendations for use. Results/Synthesis: The knee orthoses discussed within the scope of this paper are dedicated to protecting the knee against strenuous compressive loads that may affect the patellofemoral and tibiofemoral joints of the knee. Since the knee has multiple axes of motion and articulating surfaces that experience different loads during functional activities, it can be implied that, to a large extent, knee brace designs can differ drastically. Unloader knee orthoses are designed to decrease tibiofemoral and patellofemoral joint pressures. Patellofemoral knee orthoses are designed to decrease strain on the patellofemoral and quadriceps tendons while stabilizing the patella. Knee sleeves are designed to stabilize movements, reduce pain in joints, and improve proprioception across the knee joint. Conclusion: Although patients often report benefits from wearing braces, these benefits have not been confirmed by clinicians and scientific investigators. Results from these three orthosis types show that clinical efficacy is still elusive due to the different methodologies used by researchers. Layman Summary: Knee orthoses also referred to as knee brace are commonly used for support and stability of the knee. Unloader knee braces are designed to relieve and support those suffering from knee osteoarthritis by improving physical impairment and reducing pain. Patellofemoral knee braces aim to help patients manage patellofemoral pain syndrome. Rehabilitative compression sleeves, also known as knee sleeves, are often used to assist patients suffering from knee pain and laxity. Important findings on the three knee braces discussed show discrepancies in results. Their effectiveness and validity are yet to be understood.