and evaluation of periosteum-derived cells and iPSC-derived chondrocytes encapsulated in GelMA for osteochondral tissue engineering.

Osteochondral defects are deep joint surface lesions that affect the articular cartilage and the underlying subchondral bone. In the current study, a tissue engineering approach encompassing individual cells encapsulated in a biocompatible hydrogel is explored and . Cell-laden hydrogels containing either human periosteum-derived progenitor cells (PDCs) or human induced pluripotent stem cell (iPSC)-derived chondrocytes encapsulated in gelatin methacryloyl (GelMA) were evaluated for their potential to regenerate the subchondral mineralized bone and the articular cartilage on the joint surface, respectively.

Robotics-Driven Manufacturing of Cartilaginous Microtissues for Skeletal Tissue Engineering Applications.

Automated technologies are attractive for enhancing the robust manufacturing of tissue-engineered products for clinical translation. In this work, we present an automation strategy using a robotics platform for media changes, and imaging of cartilaginous microtissues cultured in static microwell platforms. We use an automated image analysis pipeline to extract microtissue displacements and morphological features as noninvasive quality attributes.

Integration of Cognitive Behavioral Therapy for Insomnia in Best-Practice Care for Patients With Knee Osteoarthritis and Insomnia: A Randomized Controlled Trial Protocol.

Objective: Knee osteoarthritis (KOA) is a common musculoskeletal problem worldwide and its key symptom is pain. Guidelines recommend incorporating comorbidity-specific therapies into patient-centered care. Patients diagnosed with KOA frequently have insomnia, which is associated with higher-pain severity.

Identifying Fibroblast Growth Factor Receptor 3 as a Mediator of Periosteal Osteochondral Differentiation through the Construction of microRNA-Based Interaction Networks.

Human periosteum-derived progenitor cells (hPDCs) have the ability to differentiate towards both the chondrogenic and osteogenic lineages. This coordinated and complex osteochondrogenic differentiation process permits endochondral ossification and is essential in bone development and repair. We have previously shown that humanised cultures of hPDCs enhance their osteochondrogenic potentials in vitro and in vivo; however, the underlying mechanisms are largely unknown.

The interplay between symptoms of insomnia and pain in people with osteoarthritis: A narrative review of the current evidence.

Osteoarthritis (OA) is a leading cause of disability worldwide and clinical pain is the major symptom of OA. This clinical OA-related pain is firmly associated with symptoms of insomnia, which are reported in up to 81% of people with OA. Since understanding the association between both symptoms is critical for their appropriate management, this narrative review synthesizes the existing evidence in people with OA on i) the mechanisms underlying the association between insomnia symptoms and clinical OA-related pain, and ii) the effectiveness of conservative non-pharmacological treatments on insomnia symptoms and clinical OA-related pain.

Stirred culture of cartilaginous microtissues promotes chondrogenic hypertrophy through exposure to intermittent shear stress.

Cartilage microtissues are promising tissue modules for bottom up biofabrication of implants leading to bone defect regeneration. Hitherto, most of the protocols for the development of these cartilaginous microtissues have been carried out in static setups, however, for achieving higher scales, dynamic process needs to be investigated. In the present study, we explored the impact of suspension culture on the cartilage microtissues in a novel stirred microbioreactor system.

Disease modification and symptom relief in osteoarthritis using a mutated GCP-2/CXCL6 chemokine.

We showed that the chemokine receptor C-X-C Motif Chemokine Receptor 2 (CXCR2) is essential for cartilage homeostasis. Here, we reveal that the CXCR2 ligand granulocyte chemotactic protein 2 (GCP-2) was expressed, during embryonic development, within the prospective permanent articular cartilage, but not in the epiphyseal cartilage destined to be replaced by bone. GCP-2 expression was retained in adult articular cartilage.

Engineering bone-forming biohybrid sheets through the integration of melt electrowritten membranes and cartilaginous microspheroids.

Bone fractures are one of the most common traumatic large-organ injuries and although many fractures can heal on their own, 2-12% of fractures are slow healing or do not heal (non-unions). Autologous grafts are currently used for treatment of non-unions but are associated with limited healthy bone tissue. Tissue engineered cell-based products have promise for an alternative treatment method.

In vitro and in vivo evaluation of 3D constructs engineered with human iPSC-derived chondrocytes in gelatin methacryloyl hydrogel.

Articular cartilage defects have limited healing potential and, when left untreated, can lead to osteoarthritis. Tissue engineering focuses on regenerating the damaged joint surface, preferably in an early stage. Here, we investigate the regenerative potential of three-dimensional (3D) constructs consisting of human induced pluripotent stem cell (iPSC)-derived chondrocytes in gelatin methacryloyl (GelMA) hydrogel for stable hyaline cartilage production.

In vivo potency assay for the screening of bioactive molecules on cartilage formation.

Cartilage regeneration is a priority in medicine for the treatment of osteoarthritis and isolated cartilage defects. Several molecules with potential for cartilage regeneration are under investigation. Unfortunately, in vitro chondrogenesis assays do not always predict the stability of the newly formed cartilage in vivo.

Human pluripotent stem cell-derived cartilaginous organoids promote scaffold-free healing of critical size long bone defects.

Background: Bones have a remarkable capacity to heal upon fracture. Yet, in large defects or compromised conditions healing processes become impaired, resulting in delayed or non-union. Current therapeutic approaches often utilize autologous or allogeneic bone grafts for bone augmentation.

Early-stage symptomatic osteoarthritis of the knee - time for action.

Osteoarthritis (OA) remains the most challenging arthritic disorder, with a high burden of disease and no available disease-modifying treatments. Symptomatic early-stage OA of the knee (the focus of this Review) urgently needs to be identified and defined, as efficient early-stage case finding and diagnosis in primary care would enable health-care providers to proactively and substantially reduce the burden of disease through proper management including structured education, exercise and weight management (when needed) and addressing lifestyle-related risk factors for disease progression. Efforts to define patient populations with symptomatic early-stage knee OA on the basis of validated classification criteria are ongoing.

Cartilaginous spheroid-assembly design considerations for endochondral ossification: towards robotic-driven biomanufacturing.

Spheroids have become essential building blocks for biofabrication of functional tissues. Spheroid formats allow high cell-densities to be efficiently engineered into tissue structures closely resembling the native tissues. In this work, we explore the assembly capacity of cartilaginous spheroids (∼ 150m) in the context of endochondral bone formation.

Reduced knee extensor torque production at low to moderate velocities in postmenopausal women with knee osteoarthritis.

This study aimed to determine deficits in knee extensor muscle function through the torque-time and torque-velocity relationships and whether these deficits are associated with reduced functional performance in postmenopausal women with knee osteoarthritis (KOA). A clinical sample of postmenopausal women with established KOA (n = 18, ≥55 years) was compared to an age-matched healthy control sample (CON) (n = 26). The deficits in different parameters of the knee extensor torque-time (maximal isometric torque and rate of torque development) and torque-velocity relationship (maximum muscle power, maximal velocity and torque at 0-500°·s ) were assessed through a protocol consisting of isometric, isotonic and isokinetic tests.

Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies.

Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates.

Impaired soft and hard callus formation during fracture healing in diet-induced obese mice as revealed by 3D contrast-enhanced computed tomography imaging.

The impact of diabetes mellitus on bone fracture healing is clinically relevant as the patients experience delayed fracture healing. Even though efforts have been made to understand the detrimental effects of type 2 diabetes mellitus (T2DM) on the fracture healing process, the exact mechanisms causing the pathophysiological outcomes remain unclear. The aim of this study was to assess alterations in bone fracture healing (tibial fracture surgery, intramedullary pinning) of diet-induced obese (DIO) mice, and to investigate the in vitro properties of osteochondroprogenitors derived from the diabetic micro-environment.

Patterned, organoid-based cartilaginous implants exhibit zone specific functionality forming osteochondral-like tissues in vivo.

Tissue engineered constructs have the potential to respond to the unmet medical need of treating deep osteochondral defects. However, current tissue engineering strategies struggle in the attempt to create patterned constructs with biologically distinct functionality. In this work, a developmentally-inspired modular approach is proposed, whereby distinct cartilaginous organoids are used as living building blocks.

Towards classification criteria for early-stage knee osteoarthritis: A population-based study to enrich for progressors.

Objective: To facilitate a greater likelihood of favorable response to new disease-modifying therapies, recruitment of patients at an earlier stage of their disease into clinical trials may be an attractive strategy. Hence, there is a need to develop widely accepted classification criteria for early-stage knee osteoarthritis (OA). We have proposed a set of classification criteria for early-stage knee OA (2018 classification criteria) now being further refined.

The Bone-Forming Properties of Periosteum-Derived Cells Differ Between Harvest Sites.

The development of alternatives for autologous bone grafts is a major focus of bone tissue engineering. To produce living bone-forming implants, skeletal stem and progenitor cells (SSPCs) are envisioned as key ingredients. SSPCs can be obtained from different tissues including bone marrow, adipose tissue, dental pulp, and periosteum.

Developmental engineering of living implants for deep osteochondral joint surface defects.

Introduction: The repair of deep osteochondral joint surface defects represents a significant unmet clinical need. Importantly, untreated lesions lead to a high rate of osteoarthritis. The current strategies to repair these defects include osteochondral autograft transplantation or "sandwich" strategies combining bone autografts with autologous chondrocyte implantation, with poorly documented long-term outcomes.

A cell-based combination product for the repair of large bone defects.

Regenerative cell-based implants using periosteum-derived stem cells were developed for the treatment of large 3 cm fresh and 4.5 centimeter biological compromised bone gaps in a tibial sheep model and compared with an acellular ceramic-collagen void filler. It was hypothesized that the latter is insufficient to heal large skeletal defects due to reduced endogenous biological potency.

Mapping human serum-induced gene networks as a basis for the creation of biomimetic periosteum for bone repair.

Background: The periosteum is a highly vascularized, collagen-rich tissue that plays a crucial role in directing bone repair. This is orchestrated primarily by its resident progenitor cell population. Indeed, preservation of periosteum integrity is critical for bone healing.