Non-hypertrophic chondrogenesis of mesenchymal stem cells through mechano-hypoxia programing.

Cartilage tissue engineering aims to generate functional replacements to treat cartilage defects from damage and osteoarthritis. Human bone marrow-derived mesenchymal stem cells (hBM-MSC) are a promising cell source for making cartilage, but current differentiation protocols require the supplementation of growth factors like TGF-β1 or -β3. This can lead to undesirable hypertrophic differentiation of hBM-MSC that progress to bone.

TEMPO-Oxidized Cellulose Nanofiber-Alginate Hydrogel as a Bioink for Human Meniscus Tissue Engineering.

The avascular inner regions of the knee menisci cannot self-heal. As a prospective treatment, functional replacements can be generated by cell-based 3D bioprinting with an appropriate cell source and biomaterial. To that end, human meniscus fibrochondrocytes (hMFC) from surgical castoffs of partial meniscectomies as well as cellulose nanofiber-alginate based hydrogels have emerged as a promising cell source and biomaterial combination.

Mechano-Hypoxia Conditioning of Engineered Human Meniscus.

Meniscus fibrochondrocytes (MFCs) experience simultaneous hypoxia and mechanical loading in the knee joint. Experimental conditions based on these aspects of the native MFC environment may have promising applications in human meniscus tissue engineering. We hypothesized that "mechano-hypoxia conditioning" with mechanical loading such as dynamic compression (DC) and cyclic hydrostatic pressure (CHP) would enhance development of human meniscus fibrocartilage extracellular matrix .

Inability of Low Oxygen Tension to Induce Chondrogenesis in Human Infrapatellar Fat Pad Mesenchymal Stem Cells.

Objective: Articular cartilage of the knee joint is avascular, exists under a low oxygen tension microenvironment, and does not self-heal when injured. Human infrapatellar fat pad-sourced mesenchymal stem cells (IFP-MSC) are an arthroscopically accessible source of mesenchymal stem cells (MSC) for the repair of articular cartilage defects. Human IFP-MSC exists physiologically under a low oxygen tension (i.

Correction: Engineered human meniscus' matrix-forming phenotype is unaffected by low strain dynamic compression under hypoxic conditions.

[This corrects the article DOI: 10.1371/journal.pone.

Engineered human meniscus' matrix-forming phenotype is unaffected by low strain dynamic compression under hypoxic conditions.

Low oxygen and mechanical loading may play roles in regulating the fibrocartilaginous phenotype of the human inner meniscus, but their combination in engineered tissues remains unstudied. Here, we investigated how continuous low oxygen ("hypoxia") combined with dynamic compression would affect the fibrocartilaginous "inner meniscus-like" matrix-forming phenotype of human meniscus fibrochondrocytes (MFCs) in a porous type I collagen scaffold. Freshly-seeded MFC scaffolds were cultured for 4 weeks in either 3 or 20% O2 or pre-cultured for 2 weeks in 3% O2 and then dynamically compressed for 2 weeks (10% strain, 1 Hz, 1 h/day, 5 days/week), all with or without TGF-β3 supplementation.

Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression.

This study investigates the transcriptome response of meniscus fibrochondrocytes (MFCs) to the low oxygen and mechanical loading signals experienced in the knee joint using a model system. We hypothesized that short term exposure to the combined treatment would promote a matrix-forming phenotype supportive of inner meniscus tissue formation. Human MFCs on a collagen scaffold were stimulated to form fibrocartilage over 6 weeks under normoxic (NRX, 20% O) conditions with supplemented TGF-β3.

Bone Marrow Mesenchymal Stem Cell-Derived Tissues are Mechanically Superior to Meniscus Cells.

Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to form the mechanically responsive matrices of joint tissues, including the menisci of the knee joint. The purpose of this study is to assess BMSC's potential to engineer meniscus-like tissue relative to meniscus fibrochondrocytes (MFCs). MFCs were isolated from castoffs of partial meniscectomy from nonosteoarthritic knees.

Calcaneal Tendon Plasticity Following Gastrocnemius Muscle Injury in Rat.

Cross-talk between skeletal muscle and tendon is important for tissue homeostasis. Whereas the skeletal muscle response to tendon injury has been well-studied, to the best of our knowledge the tendon response to skeletal muscle injury has been neglected. Thus, we investigated calcaneal tendon extracellular matrix (ECM) remodeling after gastrocnemius muscle injury using a rat model.

Mimicking "J-Shaped" and Anisotropic Stress-Strain Behavior of Human and Porcine Aorta by Fabric-Reinforced Elastomer Composites.

An ex vivo heart perfusion device preserves the donor heart in a warm beating state during transfer between extraction and implantation surgeries. One of the current challenges includes the use of rigid and noncompliant plastic tubes, which causes injuries to the heart at the junction between the tissue and the tube. The compliant and rapidly strain-stiffening mechanical property that generates a "J-shaped" stress-strain behavior is necessary for producing the Windkessel effect, which ensures continuous flow of blood through the aorta.

Re-Differentiation of Human Meniscus Fibrochondrocytes Differs in Three-Dimensional Cell Aggregates and Decellularized Human Meniscus Matrix Scaffolds.

Decellularized matrix (DCM) derived from native tissues may be a promising supporting material to induce cellular differentiation by sequestered bioactive factors. However, no previous study has investigated the use of human meniscus-derived DCM to re-differentiate human meniscus fibrochondrocytes (MFCs) to form meniscus-like extracellular matrix (ECM). We expanded human MFCs and seeded them upon a cadaveric meniscus-derived DCM prepared by physical homogenization under hypoxia.

Hypoxia and TGF-β3 Synergistically Mediate Inner Meniscus-Like Matrix Formation by Fibrochondrocytes.

The interactions of hypoxia and TGF-β3 in aggregates of human meniscus fibrochondrocytes are synergistic in nature, suggesting combinatorial strategies using these factors are promising for tissue engineering the inner meniscus regions. Hypoxia alone in the absence of TGF-β supplementation may be insufficient to initiate an inner meniscus-like extracellular matrix-forming response in this model.

Chondrogenic differentiation of synovial fluid mesenchymal stem cells on human meniscus-derived decellularized matrix requires exogenous growth factors.

The objective of this study was to investigate whether meniscus-derived decellularized matrix (DCM) has the capacity to induce differentiation of synovial fluid-derived mesenchymal stem cells (SF-MSCs) towards a meniscus fibrochondrocyte (MFC) phenotype. The potential roles of transforming growth factor beta-3 (TGF-β) and insulin-like growth factor 1 (IGF-1) in the differentiation of SF-MSCs towards an MFC phenotype were also investigated. SF-MSCs were isolated via plastic adherence cell culture from the synovial fluid of five donors (5 male, average age 34 years).

Plasticity of Human Meniscus Fibrochondrocytes: A Study on Effects of Mitotic Divisions and Oxygen Tension.

Meniscus fibrochondrocytes (MFCs) may be the optimal cell source to repair non-healing meniscus injuries using tissue engineering strategies. In this study, we investigated the effects of mitotic divisions and oxygen tension on the plasticity of adult human MFCs. Our assessment techniques included gene expression, biochemical, histological, and immunofluorescence assays.