siRNA Treatment Enhances Collagen Fiber Formation in Tissue-Engineered Meniscus via Transient Inhibition of Aggrecan Production.

The complex collagen network of the native meniscus and the gradient of the density and alignment of this network through the meniscal enthesis is essential for the proper mechanical function of these tissues. This architecture is difficult to recapitulate in tissue-engineered replacement strategies. Prenatally, the organization of the collagen fiber network is established and aggrecan content is minimal.

Bioengineered lubricin alters the lubrication modes of cartilage in a dose-dependent manner.

The low friction nature of articular cartilage has been attributed to the synergistic interaction between lubricin and hyaluronic acid in the synovial fluid (SF). Lubricin is a mucinous glycoprotein that lowers the boundary mode coefficient of friction of articular cartilage in a dose-dependent manner. While there have been multiple attempts to produce recombinant lubricin and lubricin mimetic cartilage lubricants over the last two decades, these materials have not found clinical use due to challenges associated with large scale production, manufacturing, and purification.

Timing of cartilage articulation following impact injury affects the response of surface zone chondrocytes.

Post-traumatic osteoarthritis develops following an inciting injury to a joint and results in cartilage degeneration. Mechanical loading, including articulation, drives anabolic responses in cartilage clinically, in vivo, and in vitro. Tribological articulation, or sliding of cartilage on a glass counterface, has long been used as an in vitro tool to study cartilage tissue behavior.

Specific Degradation of the Mucin Domain of Lubricin in Synovial Fluid Impairs Cartilage Lubrication.

Progressive cartilage degradation, synovial inflammation, and joint lubrication dysfunction are key markers of osteoarthritis. The composition of synovial fluid (SF) is altered in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. Lubricin's distinct bottlebrush mucin domain has been speculated to contribute to its lubricating ability, but the relationship between its structure and mechanical function in SF is not well understood.

Degradation of lubricating molecules in synovial fluid alters chondrocyte sensitivity to shear strain.

Articular joints facilitate motion and transfer loads to underlying bone through a combination of cartilage tissue and synovial fluid, which together generate a low-friction contact surface. Traumatic injury delivered to cartilage and the surrounding joint capsule causes secretion of proinflammatory cytokines by chondrocytes and the synovium, triggering cartilage matrix breakdown and impairing the ability of synovial fluid to lubricate the joint. Once these inflammatory processes become chronic, posttraumatic osteoarthritis (PTOA) development begins.

Antibacterial, Anti-Inflammatory, and Antioxidant Cotton-Based Wound Dressing Coated with Chitosan/Cyclodextrin-Quercetin Inclusion Complex Nanofibers.

Quercetin, recognized for its antioxidant, anti-inflammatory, and antibacterial properties, faces limited biomedical application due to its low solubility. Cotton, a preferred wound dressing material over synthetic ones, lacks inherent antibacterial and wound-healing attributes and can benefit from quercetin features. This study explores the potential of overcoming these challenges through the inclusion complexation of quercetin with cyclodextrins (CDs) and the development of a nanofibrous coating on a cotton nonwoven textile.

Heterogeneous distribution of viscosupplements in vivo is correlated to ex vivo frictional properties of equine cartilage.

Intra-articular injections of hyaluronic acid (HA) are the cornerstone of osteoarthritis (OA) treatments. However, the mechanism of action and efficacy of HA viscosupplementation are debated. As such, there has been recent interest in developing synthetic viscosupplements.

Customizable, biocompatible implants for dorsal nasal augmentation: An in vivo pilot study of eight polylactic acid scaffold designs.

Augmentation of the nasal dorsum often requires implantation of structural material. Existing methods include autologous, cadaveric or alloplastic materials and injectable hydrogels. Each of these options is associated with considerable limitations.

Application of a variational autoencoder for clustering and analyzing in situ articular cartilage cellular response to mechanical stimuli.

In various biological systems, analyzing how cell behaviors are coordinated over time would enable a deeper understanding of tissue-scale response to physiologic or superphysiologic stimuli. Such data is necessary for establishing both normal tissue function and the sequence of events after injury that lead to chronic disease. However, collecting and analyzing these large datasets presents a challenge-such systems are time-consuming to process, and the overwhelming scale of data makes it difficult to parse overall behaviors.

Bioengineering Full-scale auricles using 3D-printed external scaffolds and decellularized cartilage xenograft.

Reconstruction of the human auricle remains a formidable challenge for plastic surgeons. Autologous costal cartilage grafts and alloplastic implants are technically challenging, and aesthetic and/or tactile outcomes are frequently suboptimal. Using a small animal "bioreactor", we have bioengineered full-scale ears utilizing decellularized cartilage xenograft placed within a 3D-printed external auricular scaffold that mimics the size, shape, and biomechanical properties of the native human auricle.

Loss of effective lubricating viscosity is the primary mechanical marker of joint inflammation in equine synovitis.

Inflammation of the synovium, known as synovitis, plays an important role in the pathogenesis of osteoarthritis (OA). Synovitis involves the release of a wide variety of pro-inflammatory mediators in synovial fluid (SF) that damage the articular cartilage extracellular matrix and induce death and apoptosis in chondrocytes. The composition of synovial fluid is dramatically altered by inflammation in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF.

Finite element modeling to predict the influence of anatomic variation and implant placement on performance of biological intervertebral disc implants.

Background: Tissue-engineered intervertebral disc (TE-IVD) constructs are an attractive therapy for treating degenerative disc disease and have previously been investigated in vivo in both large and small animal models. The mechanical environment of the spine is notably challenging, in part due to its complex anatomy, and implants may require additional mechanical support to avoid failure in the early stages of implantation. As such, the design of suitable support implants requires rigorous validation.

Microscale strain concentrations in tissue-engineered osteochondral implants are dictated by local compositional thresholds and architecture.

Tissue-engineered osteochondral implants manufactured from condensed mesenchymal stem cell bodies have shown promise for treating focal cartilage defects. Notably, such manufacturing techniques have shown to successfully recapture the bulk mechanical properties of native cartilage. However, the relationships among the architectural features, local composition, and micromechanical environment within tissue-engineered cartilage from cell-based aggregates remain unclear.

Alginate Conjugation Increases Toughness in Auricular Chondrocyte Seeded Collagen Hydrogels.

Current auricular cartilage replacements for pediatric microtia fail to address the need for long-term integration and neocartilage formation. While collagen hydrogels have been successful in fostering neocartilage formation, the toughness and extensibility of these materials do not match that of native tissue. This study used the N-terminal functionalization of collagen with alginate oligomers to improve toughness and extensibility through metal-ion complexation.

Instabilities induced by mechanical loading determine the viability of chondrocytes grown on porous scaffolds.

Tissue-engineered cartilage constructs have shown promise to treat focal cartilage defects in multiple clinical studies. Notably, products in clinical use or in late-stage clinical trials often utilize porous collagen scaffolds to provide mechanical support and attachment sites for chondrocytes. Under loading, both the local mechanical responses of collagen scaffolds and the corresponding cellular outcomes are poorly understood, despite their wide use.

Understanding the Influence of Local Physical Stimuli on Chondrocyte Behavior.

Investigating the mechanobiology of chondrocytes is challenging due to the complex micromechanical environment of cartilage tissue. The innate zonal differences and poroelastic properties of the tissue combined with its heterogeneous composition create spatial- and temporal-dependent cell behavior, which further complicates the investigation. Despite the numerous challenges, understanding the mechanobiology of chondrocytes is crucial for developing strategies for treating cartilage related diseases as chondrocytes are the only cell type within the tissue.

Removal of GAGs Regulates Mechanical Properties, Collagen Fiber Formation, and Alignment in Tissue Engineered Meniscus.

The complex fibrillar architecture of native meniscus is essential for proper function and difficult to recapitulate in vitro. In the native meniscus, proteoglycan content is low during the development of collagen fibers and progressively increases with aging. In vitro, fibrochondrocytes produce glycosaminoglycans (GAGs) early in culture, in contrast to native tissue, where they are deposited after collagen fibers have formed.

Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress.

Articular cartilage has limited healing capacity and no drugs are available that can prevent or slow the development of osteoarthritis (OA) after joint injury. Mesenchymal stromal cell (MSC)-based regenerative therapies for OA are increasingly common, but questions regarding their mechanisms of action remain. Our group recently reported that although cartilage is avascular and relatively metabolically quiescent, injury induces chondrocyte mitochondrial dysfunction, driving cartilage degradation and OA.

STRAINS: A big data method for classifying cellular response to stimuli at the tissue scale.

Cellular response to stimulation governs tissue scale processes ranging from growth and development to maintaining tissue health and initiating disease. To determine how cells coordinate their response to such stimuli, it is necessary to simultaneously track and measure the spatiotemporal distribution of their behaviors throughout the tissue. Here, we report on a novel SpatioTemporal Response Analysis IN Situ (STRAINS) tool that uses fluorescent micrographs, cell tracking, and machine learning to measure such behavioral distributions.

Controlling collagen gelation pH to enhance biochemical, structural, and biomechanical properties of tissue-engineered menisci.

Collagen-based hydrogels have been widely used in biomedical applications due to their biocompatibility. Enhancing mechanical properties of collagen gels remains challenging while maintaining biocompatibility. Here, we demonstrate that gelation pH has profound effects on cellular activity, collagen fibril structure, and mechanical properties of the fibrochondrocyte-seeded collagen gels in both short- and long-terms.

Pre-glycation impairs gelation of high concentration collagen solutions.

There remains a need for stiffer collagen hydrogels for tissue engineering and disease modeling applications. Pre-glycation, or glycation of collagen in solution prior to gelation, has been shown to increase the mechanics of collagen hydrogels while maintaining high viability of encapsulated cells. The stiffness of glycated collagen gels can be increased by increasing the collagen concentration, sugar concentration, and glycation time.

Simple synthesis of soft, tough, and cytocompatible biohybrid composites.

Collagen is the most abundant component of mammalian extracellular matrices. As such, the development of materials that mimic the biological and mechanical properties of collagenous tissues is an enduring goal of the biomaterials community. Despite the development of molded and 3D printed collagen hydrogel platforms, their use as biomaterials and tissue engineering scaffolds is hindered by either low stiffness and toughness or processing complexity.

Efficient engineering of human auricular cartilage through mesenchymal stem cell chaperoning.

A major challenge to the clinical translation of tissue-engineered ear scaffolds for ear reconstruction is the limited auricular chondrocyte (hAuC) yield available from patients. Starting with a relatively small number of chondrocytes in culture results in dedifferentiation and loss of phenotype with subsequent expansion. To significantly decrease the number of chondrocytes required for human elastic cartilage engineering, we co-cultured human mesenchymal stem cells (hMSCs) with HAuCs to promote healthy elastic cartilage formation.