Biocompatibility Study of Purified and Low-Temperature-Sterilized Injectable Collagen for Soft Tissue Repair: Intramuscular Implantation in Rats.

The clinical application of collagen-based biomaterials is expanding rapidly, especially in tissue engineering and cosmetics. While oral supplements and injectable skin boosters are popular for enhancing skin health, clinical evidence supporting their effectiveness remains limited. Injectable products show potential in revitalizing skin, but safety concerns persist due to challenges in sterilization and the risk of biological contamination.

Challenges Facing the Translation of Embryonic Stem Cell Therapy for the Treatment of Cartilage Lesions.

Osteoarthritis is a common disease resulting in significant disability without approved disease-modifying treatment (other than total joint replacement). Stem cell-based therapy is being actively explored for the repair of cartilage lesions in the treatment and prevention of osteoarthritis. Embryonic stem cells are a very attractive source as they address many of the limitations inherent in autologous stem cells, such as variability in function and limited expansion.

ALK-5 Inhibitors for Efficient Derivation of Mesenchymal Stem Cells from Human Embryonic Stem Cells.

Successful tissue regeneration requires a clinically viable source of mesenchymal stem cells (MSCs). We explored activin receptor-like kinase (ALK)-5 inhibitors to rapidly derive an MSC-like phenotype with high cartilage forming capacity from a xeno-free human embryonic cell line. Embryonic stem cell (ESC) lines (H9 and HADC100) were treated with the ALK-5 inhibitor SB431542; HADC100 cells were additionally treated with ALK-5 inhibitors SB525334 or GW788388.

Pneumatospinning Biomimetic Scaffolds for Meniscus Tissue Engineering.

Nanofibrous scaffolds fabricated via electrospinning have been proposed for meniscus tissue regeneration. However, the electrospinning process is slow, and can only generate scaffolds of limited thickness with densely packed fibers, which limits cell distribution within the scaffold. In this study, we explored whether pneumatospinning could produce thicker collagen type I fibrous scaffolds with higher porosity, that can support cell infiltration and neo-fibrocartilage tissue formation for meniscus tissue engineering.

Mohawk is a transcription factor that promotes meniscus cell phenotype and tissue repair and reduces osteoarthritis severity.

Meniscus tears are common knee injuries and a major osteoarthritis (OA) risk factor. Knowledge gaps that limit the development of therapies for meniscus injury and degeneration concern transcription factors that control the meniscus cell phenotype. Analysis of RNA sequencing data from 37 human tissues in the Genotype-Tissue Expression database and RNA sequencing data from meniscus and articular cartilage showed that transcription factor Mohawk (MKX) is highly enriched in meniscus.

Meniscal tissue repair with nanofibers: future perspectives.

The knee menisci are critical to the long-term health of the knee joint. Because of the high incidence of injury and degeneration, replacing damaged or lost meniscal tissue is extremely clinically relevant. The multiscale architecture of the meniscus results in unique biomechanical properties.

FOXO1 and FOXO3 transcription factors have unique functions in meniscus development and homeostasis during aging and osteoarthritis.

The objective of this study was to examine FoxO expression and FoxO function in meniscus. In menisci from human knee joints with osteoarthritis (OA), FoxO1 and 3 expression were significantly reduced compared with normal menisci from young and old normal donors. The expression of FoxO1 and 3 was also significantly reduced in mouse menisci during aging and OA induced by surgical meniscus destabilization or mechanical overuse.

Cartilage tissue engineering combining microspheroid building blocks and microneedle arrays.

: Scaffold-free cartilage tissue engineering circumvents issues with scaffold seeding, potential toxicity response, and impaired host integration. However, precisely controlling and maintaining a scaffold-free construct shape have been challenging. We explored the feasibility of microneedle arrays to print tissue using cellular microspheroids as building blocks.

Development of an Murine Osteochondral Repair Model.

Objective: Mouse models are commonly used in research applications due to the relatively low cost, highly characterized strains, as well as the availability of many genetically modified phenotypes. In this study, we characterized an murine osteochondral repair model using human infrapatellar fat pad (IPFP) progenitor cells.

Design: Femurs from euthanized mice were removed and clamped in a custom multidirectional vise to create cylindrical osteochondral defects 0.

Gene expression profiles of the meniscus avascular phenotype: A guide for meniscus tissue engineering.

Avascular (Avas) meniscus regeneration remains a challenge, which is partly a consequence of our limited knowledge of the cells that maintain this tissue region. In this study, we utilized microarrays to characterize gene expression profiles of intact human Avas meniscus tissue and of cells following culture expansion. Using these data, we examined various 3D culture conditions to redifferentiate Avas cells toward the tissue phenotype.

Meniscal Tissue Engineering Using Aligned Collagen Fibrous Scaffolds: Comparison of Different Human Cell Sources.

Hydrogel and electrospun scaffold materials support cell attachment and neotissue development and can be tuned to structurally and mechanically resemble native extracellular matrix by altering either electrospun fiber or hydrogel properties. In this study, we examined meniscus tissue generation from different human cell sources including meniscus cells derived from vascular and avascular regions, human bone marrow-derived mesenchymal stem cells, synovial cells, and cells from the infrapatellar fat pad (IPFP). All cells were seeded onto aligned electrospun collagen type I scaffolds and were optionally encapsulated in a tricomponent hydrogel.

Relevance of meniscal cell regional phenotype to tissue engineering.

Purpose: Meniscus contains heterogeneous populations of cells that have not been fully characterized. Cell phenotype is often lost during culture; however, culture expansion is typically required for tissue engineering. We examined and compared cell-surface molecule expression levels on human meniscus cells from the vascular and avascular regions and articular chondrocytes while documenting changes during culture-induced dedifferentiation.

Repair of Avascular Meniscus Tears with Electrospun Collagen Scaffolds Seeded with Human Cells.

The self-healing capacity of an injured meniscus is limited to the vascularized regions and is especially challenging in the inner avascular regions. As such, we investigated the use of human meniscus cell-seeded electrospun (ES) collagen type I scaffolds to produce meniscal tissue and explored whether these cell-seeded scaffolds can be implanted to repair defects created in meniscal avascular tissue explants. Human meniscal cells (derived from vascular and avascular meniscal tissue) were seeded on ES scaffolds and cultured.

Control of Retinal Ganglion Cell Positioning and Neurite Growth: Combining 3D Printing with Radial Electrospun Scaffolds.

Retinal ganglion cells (RGCs) are responsible for the transfer of signals from the retina to the brain. As part of the central nervous system, RGCs are unable to regenerate following injury, and implanted cells have limited capacity to orient and integrate in vivo. During development, secreted guidance molecules along with signals from extracellular matrix and the vasculature guide cell positioning, for example, around the fovea, and axon outgrowth; however, these changes are temporally regulated and are not the same in the adult.

Evaluation of bound and pore water in cortical bone using ultrashort-TE MRI.

Bone water exists in different states with the majority bound to the organic matrix and to mineral, and a smaller fraction in 'free' form in the pores of cortical bone. In this study, we aimed to develop and evaluate ultrashort-TE (UTE) MRI techniques for the assessment of T2*, T1 and concentration of collagen-bound and pore water in cortical bone using a 3-T clinical whole-body scanner. UTE MRI, together with an isotope study using tritiated and distilled water (THO-H2O) exchange, as well as gravimetric analysis, were performed on ten sectioned bovine bone samples.

Meniscus tissue engineering using a novel combination of electrospun scaffolds and human meniscus cells embedded within an extracellular matrix hydrogel.

Meniscus injury and degeneration have been linked to the development of secondary osteoarthritis (OA). Therapies that successfully repair or replace the meniscus are, therefore, likely to prevent or delay OA progression. We investigated the novel approach of building layers of aligned polylactic acid (PLA) electrospun (ES) scaffolds with human meniscus cells embedded in extracellular matrix (ECM) hydrogel to lead to formation of neotissues that resemble meniscus-like tissue.

Atomic force microscopy reveals age-dependent changes in nanomechanical properties of the extracellular matrix of native human menisci: implications for joint degeneration and osteoarthritis.

Unlabelled: With aging, the menisci become more susceptible to degeneration due to sustained mechanical stress accompanied by age-related changes in the extracellular matrix (ECM). However, the mechanistic relationship between age-related meniscal degeneration and osteoarthritis (OA) development is not yet fully understood. We have examined the nanomechanical properties of the ECM of normal, aged, and degenerated human menisci using atomic force microscopy (AFM).

Repair of cartilage defects in arthritic tissue with differentiated human embryonic stem cells.

Chondrocytes have been generated in vitro from a range of progenitor cell types and by a number of strategies. However, achieving reconstitution of actual physiologically relevant, appropriately-laminated cartilage in situ that would be applicable to conditions, such as arthritis and cartilage degeneration remains elusive. This lack of success is multifactorial and includes limited cell source, decreased proliferation rate of mature chondrocytes, lack of maintenance of phenotype, reduced matrix synthesis, and poor integration with host tissue.

Influence of cartilage extracellular matrix molecules on cell phenotype and neocartilage formation.

Interaction between chondrocytes and the cartilage extracellular matrix (ECM) is essential for maintaining the cartilage's role as a low-friction and load-bearing tissue. In this study, we examined the influence of cartilage zone-specific ECM on human articular chondrocytes (HAC) in two-dimensional and three-dimensional (3D) environments. Two culture systems were used.

Digital micromirror device projection printing system for meniscus tissue engineering.

Meniscus degeneration due to age or injury can lead to osteoarthritis. Although promising, current cell-based approaches show limited success. Here we present three-dimensional methacrylated gelatin (GelMA) scaffolds patterned via projection stereolithography to emulate the circumferential alignment of cells in native meniscus tissue.

Osteoarthritis: detection, pathophysiology, and current/future treatment strategies.

Osteoarthritis (OA) is a disease of the joint, and age is the major risk factor for its development. Clinical manifestation of OA includes joint pain, stiffness, and loss of mobility. Currently, no pharmacological treatments are available to treat this specific joint disease; only symptom-modifying drugs are available.

Zone-specific gene expression patterns in articular cartilage.

Objective: To identify novel genes and pathways specific to the superficial zone (SZ), middle zone (MZ), and deep zone (DZ) of normal articular cartilage.

Methods: Articular cartilage was obtained from the knees of 4 normal human donors. The cartilage zones were dissected on a microtome.

Effects of perfusion and dynamic loading on human neocartilage formation in alginate hydrogels.

Dynamic loading and perfusion culture environments alone are known to enhance cartilage extracellular matrix (ECM) production in dedifferentiated articular chondrocytes. In this study, we explored whether a combination of these factors would enhance these processes over a free-swelling (FS) condition using adult human articular chondrocytes embedded in 2% alginate. The alginate constructs were placed into a bioreactor for perfusion (P) only (100 μL/per minute) or perfusion and dynamic compressive loading (PL) culture (20% for 1 h, at 0.

In situ tissue engineering using magnetically guided three-dimensional cell patterning.

Manipulation of cell patterns in three dimensions in a manner that mimics natural tissue organization and function is critical for cell biological studies and likely essential for successfully regenerating tissues--especially cells with high physiological demands, such as those of the heart, liver, lungs, and articular cartilage.(1, 2) In the present study, we report on the feasibility of arranging iron oxide-labeled cells in three-dimensional hydrogels using magnetic fields. By manipulating the strength, shape, and orientation of the magnetic field and using crosslinking gradients in hydrogels, multi-directional cell arrangements can be produced in vitro and even directly in situ.