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Bioactive Materials Jul 2023The necessity of disease models for bone/cartilage related disorders is well-recognized, but the barrier between cell culture, animal models and the real human body has... (Review)
Review
The necessity of disease models for bone/cartilage related disorders is well-recognized, but the barrier between cell culture, animal models and the real human body has been pending for decades. The organoid-on-a-chip technique showed opportunity to revolutionize basic research and drug screening for diseases like osteoporosis and arthritis. The bone/cartilage organoid on-chip (BCoC) system is a novel platform of multi-tissue which faithfully emulate the essential elements, biologic functions and pathophysiological response under real circumstances. In this review, we propose the concept of BCoC platform, summarize the basic modules and current efforts to orchestrate them on a single microfluidic system. Current disease models, unsolved problems and future challenging are also discussed, the aim should be a deeper understanding of diseases, and ultimate realization of generic tools for further therapeutic strategies of pathological conditions.
PubMed: 37056252
DOI: 10.1016/j.bioactmat.2023.01.016 -
Nature Communications Oct 2023Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we...
Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we present an injectable, biodegradable piezoelectric hydrogel, made of short electrospun poly-L-lactic acid nanofibers embedded inside a collagen matrix, which can be injected into the joints and self-produce localized electrical cues under ultrasound activation to drive cartilage healing. In vitro, data shows that the piezoelectric hydrogel with ultrasound can enhance cell migration and induce stem cells to secrete TGF-β1, which promotes chondrogenesis. In vivo, the rabbits with osteochondral critical-size defects receiving the ultrasound-activated piezoelectric hydrogel show increased subchondral bone formation, improved hyaline-cartilage structure, and good mechanical properties, close to healthy native cartilage. This piezoelectric hydrogel is not only useful for cartilage healing but also potentially applicable to other tissue regeneration, offering a significant impact on the field of regenerative tissue engineering.
Topics: Humans; Animals; Rabbits; Hydrogels; Cartilage; Collagen; Wound Healing; Cells, Cultured; Chondrogenesis; Tissue Engineering; Tissue Scaffolds; Cartilage, Articular
PubMed: 37802985
DOI: 10.1038/s41467-023-41594-y -
Bioactive Materials Sep 2023The regeneration of hierarchical osteochondral units is challenging due to difficulties in inducing spatial, directional and controllable differentiation of mesenchymal...
The regeneration of hierarchical osteochondral units is challenging due to difficulties in inducing spatial, directional and controllable differentiation of mesenchymal stem cells (MSCs) into cartilage and bone compartments. Emerging organoid technology offers new opportunities for osteochondral regeneration. In this study, we developed gelatin-based microcryogels customized using hyaluronic acid (HA) and hydroxyapatite (HYP), respectively for inducing cartilage and bone regeneration (denoted as CH-Microcryogels and OS-Microcryogels) through self-assembly into osteochondral organoids. The customized microcryogels showed good cytocompatibility and induced chondrogenic and osteogenic differentiation of MSCs, while also demonstrating the ability to self-assemble into osteochondral organoids with no delamination in the biphasic cartilage-bone structure. Analysis by mRNA-seq showed that CH-Microcryogels promoted chondrogenic differentiation and inhibited inflammation, while OS-Microcryogels facilitated osteogenic differentiation and suppressed the immune response, by regulating specific signaling pathways. Finally, the engraftment of pre-differentiated customized microcryogels into canine osteochondral defects resulted in the spontaneous assembly of an osteochondral unit, inducing simultaneous regeneration of both articular cartilage and subchondral bone. In conclusion, this novel approach for generating self-assembling osteochondral organoids utilizing tailor-made microcryogels presents a highly promising avenue for advancing the field of tissue engineering.
PubMed: 37096194
DOI: 10.1016/j.bioactmat.2023.04.002 -
Advanced Science (Weinheim,... Sep 2023In clinical practice, repairing osteochondral defects presents a challenge due to the varying biological properties of articular cartilages and subchondral bones. Thus,...
In clinical practice, repairing osteochondral defects presents a challenge due to the varying biological properties of articular cartilages and subchondral bones. Thus, elucidating how spatial microenvironment-specific biomimetic scaffolds can be used to simultaneously regenerate osteochondral tissue is an important research topic. Herein, a novel bioinspired double-network hydrogel scaffold produced via 3D printing with tissue-specific decellularized extracellular matrix (dECM) and human adipose mesenchymal stem cell (MSC)-derived exosomes is described. The bionic hydrogel scaffolds promote rat bone marrow MSC attachment, spread, migration, proliferation, and chondrogenic and osteogenic differentiation in vitro, as determined based on the sustained release of bioactive exosomes. Furthermore, the 3D-printed microenvironment-specific heterogeneous bilayer scaffolds efficiently accelerate the simultaneous regeneration of cartilage and subchondral bone tissues in a rat preclinical model. In conclusion, 3D dECM-based microenvironment-specific biomimetics encapsulated with bioactive exosomes can serve as a novel cell-free recipe for stem cell therapy when treating injured or degenerative joints. This strategy provides a promising platform for complex zonal tissue regeneration whilst holding attractive clinical translation potential.
Topics: Rats; Humans; Animals; Tissue Scaffolds; Osteogenesis; Hydrogels; Exosomes; Cartilage; Bone Regeneration; Printing, Three-Dimensional
PubMed: 37424038
DOI: 10.1002/advs.202303650 -
Cureus Oct 2023Platelet-rich plasma (PRP) as a treatment modality has been around for the last four decades, but only truly gained popularity over the last 10 to 15 years in medicine,... (Review)
Review
Platelet-rich plasma (PRP) as a treatment modality has been around for the last four decades, but only truly gained popularity over the last 10 to 15 years in medicine, in a variety of fields ranging from regenerative medicine to infertility treatment. It has gained popularity, especially in treating musculoskeletal conditions where the bulk of research has been performed and published. There is level I evidence available supporting its efficacy in the treatment of osteoarthritis (OA), epicondylitis, bursitis, compressive neuropathy, plantar fasciitis, muscular injuries and osteochondral lesions. Most published research with regards to PRP has been focused on knee OA (limited research in shoulder, elbow, and foot and ankle OA), lateral epicondylitis and carpal tunnel syndrome, whereas spinal and hand conditions have limited research available. Tendinopathies and partial tendon tears have conflicting evidence available, with level I evidence supporting PRP's use in rotator cuff tendinopathies and tears, with contradictory level I evidence discouraging its use in patella and Achilles tendinopathies and tears. The available evidence regarding the use of PRP continues to produce conflicting results, but despite this, there is an ongoing increase in the popularity and use of PRP in patients with musculoskeletal conditions.
PubMed: 38021947
DOI: 10.7759/cureus.47176 -
Journal of Clinical Medicine Oct 2023Many patients, particularly those aged above 40, experience knee joint pain, which hampers both sports activities and daily living. Treating isolated chondral and... (Review)
Review
Many patients, particularly those aged above 40, experience knee joint pain, which hampers both sports activities and daily living. Treating isolated chondral and osteochondral defects in the knee poses a significant clinical challenge, particularly in younger patients who are not typically recommended partial or total knee arthroplasty as alternatives. Several surgical approaches have been developed to address focal cartilage defects. The treatment strategies are characterized as palliation (e.g., chondroplasty and debridement), repair (e.g., drilling and microfracture), or restoration (e.g., autologous chondrocyte implantation, osteochondral autograft, and osteochondral allograft). This review offers an overview of the commonly employed clinical methods for treating articular cartilage defects, with a specific focus on the clinical trials conducted in the last decade. Our study reveals that, currently, no single technology fully meets the essential requirements for effective cartilage healing while remaining easily applicable during surgical procedures. Nevertheless, numerous methods are available, and the choice of treatment should consider factors such as the location and size of the cartilage lesion, patient preferences, and whether it is chondral or osteochondral in nature. Promising directions for the future include tissue engineering, stem cell therapies, and the development of pre-formed scaffolds from hyaline cartilage, offering hope for improved outcomes.
PubMed: 37892577
DOI: 10.3390/jcm12206434