Co-transfection of decorin and interleukin-10 modulates pro-fibrotic extracellular matrix gene expression in human tenocyte culture

Extracellular matrix synthesis and remodelling are driven by increased activity of transforming growth factor beta 1 (TGF-beta 1). In tendon tissue repair, increased activity of TGF-beta 1 leads to progressive fibrosis. Decorin (DCN) and interleukin 10 (IL-10) antagonise pathological collagen synthesis by exerting a neutralising effect via downregulation of TGF-beta 1. Herein, we report that the delivery of DCN and IL-10 transgenes from a collagen hydrogel system supresses the constitutive expression of TGF-beta 1 and a range of pro-fibrotic extracellular matrix genes

Co-transfection of decorin and interleukin-10 modulates pro-fibrotic extracellular matrix gene expression in human tenocyte culture

Extracellular matrix synthesis and remodelling are driven by increased activity of transforming growth factor beta 1 (TGF-beta 1). In tendon tissue repair, increased activity of TGF-beta 1 leads to progressive fibrosis. Decorin (DCN) and interleukin 10 (IL-10) antagonise pathological collagen synthesis by exerting a neutralising effect via downregulation of TGF-beta 1. Herein, we report that the delivery of DCN and IL-10 transgenes from a collagen hydrogel system supresses the constitutive expression of TGF-beta 1 and a range of pro-fibrotic extracellular matrix genes

D-glucosamine-based supramolecular hydrogels to improve wound healing

A simple supramolecular hydrogel based on D-glucosamine, a naturally occurring aminosaccharide, promises new biomaterials for applications such as wound healing

Implantation of hyaluronic acid hydrogel prevents the pain phenotype in a rat model of intervertebral disc injury

Painful intervertebral disc degeneration is mediated by inflammation that modulates glycosylation and induces hyperinnervation and sensory sensitization, which result in discogenic pain. Hyaluronic acid (HA) used as a therapeutic biomaterial can reduce inflammation and pain, but the effects ofHA therapy on glycosylation and pain associated with disc degeneration have not been previously determined. We describe a novel rat model of pain induced by intervertebral disc injury, with validation of the pain phenotype by morphine treatment. Using this model, we assessed the efficacy of HA hydrogel for the alleviation of pain, demonstrating that it reduced nociceptive behavior, an effect associated with down-regulation of nociception markers and inhibition of hyperinnervation. Furthermore, HA hydrogel altered glycosylation and modulated key inflammatory and regulatory signaling pathways, resulting in attenuation of inflammation and regulation of matrix components. Our results suggest that HA hydrogel is a promising clinical candidate for the treatment of back pain caused by degenerated discs

Harnessing hierarchical nano- and micro-fabrication technologies for musculoskeletal tissue engineering

Cells within a tissue are able to perceive, interpret and respond to the biophysical, biomechanical, and biochemical properties of the 3D extracellular matrix environment in which they reside. Such stimuli regulate cell adhesion, metabolic state, proliferation, migration, fate and lineage commitment, and ultimately, tissue morphogenesis and function. Current scaffold fabrication strategies in musculoskeletal tissue engineering seek to mimic the sophistication and comprehensiveness of nature to develop hierarchically assembled 3D implantable devices of different geometric dimensions (nano-to macrometric scales) that will offer control over cellular functions and ultimately achieve functional regeneration. Herein, advances and shortfalls of bottom-up (self-assembly, freeze-drying, rapid prototype, electrospinning) and top-down (imprinting) scaffold fabrication approaches, specific to musculoskeletal tissue engineering, are discussed and critically assessed

Harnessing hierarchical nano- and micro-fabrication technologies for musculoskeletal tissue engineering

Cells within a tissue are able to perceive, interpret and respond to the biophysical, biomechanical, and biochemical properties of the 3D extracellular matrix environment in which they reside. Such stimuli regulate cell adhesion, metabolic state, proliferation, migration, fate and lineage commitment, and ultimately, tissue morphogenesis and function. Current scaffold fabrication strategies in musculoskeletal tissue engineering seek to mimic the sophistication and comprehensiveness of nature to develop hierarchically assembled 3D implantable devices of different geometric dimensions (nano-to macrometric scales) that will offer control over cellular functions and ultimately achieve functional regeneration. Herein, advances and shortfalls of bottom-up (self-assembly, freeze-drying, rapid prototype, electrospinning) and top-down (imprinting) scaffold fabrication approaches, specific to musculoskeletal tissue engineering, are discussed and critically assessed

Harnessing hierarchical nano- and micro-fabrication technologies for musculoskeletal tissue engineering

Cells within a tissue are able to perceive, interpret and respond to the biophysical, biomechanical, and biochemical properties of the 3D extracellular matrix environment in which they reside. Such stimuli regulate cell adhesion, metabolic state, proliferation, migration, fate and lineage commitment, and ultimately, tissue morphogenesis and function. Current scaffold fabrication strategies in musculoskeletal tissue engineering seek to mimic the sophistication and comprehensiveness of nature to develop hierarchically assembled 3D implantable devices of different geometric dimensions (nano-to macrometric scales) that will offer control over cellular functions and ultimately achieve functional regeneration. Herein, advances and shortfalls of bottom-up (self-assembly, freeze-drying, rapid prototype, electrospinning) and top-down (imprinting) scaffold fabrication approaches, specific to musculoskeletal tissue engineering, are discussed and critically assessed

Silk Fibroin-Based Complex Particles with Bioactive Encrustation for Bone Morphogenetic Protein 2 Delivery

Application of bone morphogenetic protein 2 (BMP-2) currently faces its challenges, and its efficacy of delivery has to be improved. The proper dosage of the powerful bioactive molecule is still under discussion and needs to be investigated further. In this work, pure silk fibroin particles and particles with calcium carbonate encrustation (complex particles) are designed, developed, and functionalized by BMP-2. These are used to deliver the bioactive molecule to mesenchymal stem cells (MSCs) to induce osteogenic differentiation. Results are compared with those of control groups of BMP-2 carriers under the same condition. Silk fibroin-based particles with size and component variations are prepared by self-assembly, desolvation, and soft template formation to improve BMP-2 loading efficiency. Results show that the particles significantly enhance osteogenic differentiation of MSCs, which is evident in the high ALP enzyme activity as well as the increased level of expression of osteogenic genes. Specifically, the combination of calcium compound and BMP-2 in the silk fibroin–calcium carbonate complex particles synergistically enhances osteogenesis. Release tests and mathematical modeling are applied to describe BMP-2 dissolution profiles, and the release mechanism is based on diffusion and polymer chain relaxation. In summary, the particles show high efficacies of BMP-2 delivery, and introduction of the complex particle can progressively enhance osteogenesis