Conditioning the microenvironment for soft tissue regeneration in a cell free scaffold.
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ABSTRACT:
SUBMITTER: Gerges I
PROVIDER: S-EPMC8233309 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Soft tissue fillers are needed for restoration of a defect or augmentation of existing tissues. Autografts and lipotransfer have been under study for soft tissue reconstruction but yield inconsistent results, often with considerable resorption of the grafted tissue. A minimally invasive procedure would reduce scarring and recovery time as well as allow the implant and/or grafted tissue to be placed closer to existing vasculature. Here, the feasibility of an injectable silk foam for soft tissue regeneration is demonstrated. Adipose-derived stem cells survive and migrate through the foam over a 10-d period in vitro. The silk foams are also successfully injected into the subcutaneous space in a rat and over a 3-month period integrating with the surrounding native tissue. The injected foams are palpable and soft to the touch through the skin and returning to their original dimensions after pressure is applied and then released. The foams readily absorb lipoaspirate making the foams useful as a scaffold or template for existing soft tissue filler technologies, useful either as a biomaterial alone or in combination with the lipoaspirate.
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Project description:Tissue-engineered blood vessels (TEBV) can serve as vascular grafts and may also play an important role in the development of organs-on-a-chip. Most TEBV construction involves scaffolding with biomaterials such as collagen gel or electrospun fibrous mesh. Hypothesizing that a scaffold-free TEBV may be advantageous, we constructed a tubular structure (1 mm i.d.) from aligned human mesenchymal cell sheets (hMSC) as the wall and human endothelial progenitor cell (hEPC) coating as the lumen. The burst pressure of the scaffold-free TEBV was above 200 mmHg after three weeks of sequential culture in a rotating wall bioreactor and perfusion at 6.8 dynes/cm(2). The interwoven organization of the cell layers and extensive extracellular matrix (ECM) formation of the hMSC-based TEBV resembled that of native blood vessels. The TEBV exhibited flow-mediated vasodilation, vasoconstriction after exposure to 1 μM phenylephrine and released nitric oxide in a manner similar to that of porcine femoral vein. HL-60 cells attached to the TEBV lumen after TNF-α activation to suggest a functional endothelium. This study demonstrates the potential of a hEPC endothelialized hMSC-based TEBV for drug screening.
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Project description:Blinding corneal scarring is predominately treated with allogeneic graft tissue; however, there is a worldwide shortage of donor tissue leaving millions in need of therapy. Human corneal stromal stem cells (CSSC) have been shown produce corneal tissue when cultured on nanofibre scaffolding, but this tissue cannot be readily separated from the scaffold. In this study, scaffold-free tissue engineering methods were used to generate biomimetic corneal stromal tissue constructs that can be transplanted in vivo without introducing the additional variables associated with exogenous scaffolding. CSSC were cultured on substrates with aligned microgrooves, which directed parallel cell alignment and matrix organization, similar to the organization of native corneal stromal lamella. CSSC produced sufficient matrix to allow manual separation of a tissue sheet from the grooved substrate. These constructs were cellular and collagenous tissue sheets, approximately 4 μm thick and contained extracellular matrix molecules typical of corneal tissue including collagen types I and V and keratocan. Similar to the native corneal stroma, the engineered corneal tissues contained long parallel collagen fibrils with uniform diameter. After being transplanted into mouse corneal stromal pockets, the engineered corneal stromal tissues became transparent, and the human CSSCs continued to express human corneal stromal matrix molecules. Both in vitro and in vivo, these scaffold-free engineered constructs emulated stromal lamellae of native corneal stromal tissues. Scaffold-free engineered corneal stromal constructs represent a novel, potentially autologous, cell-generated, biomaterial with the potential for treating corneal blindness. Copyright © 2016 John Wiley & Sons, Ltd.
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Project description:Current limitations of exogenous scaffolds or extracellular matrix based materials have underlined the need for alternative tissue-engineering solutions. Scaffolds may elicit adverse host responses and interfere with direct cell-cell interaction, as well as assembly and alignment of cell-produced ECM. Thus, fabrication techniques for production of scaffold-free engineered tissue constructs have recently emerged. Here we report on a fully biological self-assembly approach, which we implement through a rapid prototyping bioprinting method for scaffold-free small diameter vascular reconstruction. Various vascular cell types, including smooth muscle cells and fibroblasts, were aggregated into discrete units, either multicellular spheroids or cylinders of controllable diameter (300-500 microm). These were printed layer-by-layer concomitantly with agarose rods, used here as a molding template. The post-printing fusion of the discrete units resulted in single- and double-layered small diameter vascular tubes (OD ranging from 0.9 to 2.5mm). A unique aspect of the method is the ability to engineer vessels of distinct shapes and hierarchical trees that combine tubes of distinct diameters. The technique is quick and easily scalable.
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Project description:A significant body of research has considered collagen as a scaffold material for soft tissue regeneration. The main structural component of extra-cellular matrix (ECM), collagen's advantages over synthetic polymers are numerous. However, for applications where higher stiffness and stability are required, significant cross-linking may affect bioactivity. A carbodiimide (EDC) cross-linking route consumes carboxylate groups that are key to collagen's essential cell recognition motifs (GxOGER). Fibrinogen was considered as a promising additive as it plays a key role in the process of wound repair and contains RGD integrin binding sites which bind to a variety of cells, growth factors and cytokines. Fibrinogen's binding sites however, also contain the same carboxylate groups as collagen. We have successfully produced highly interconnected, porous collagen-fibrinogen scaffolds using a lyophilisation technique and micro-computed tomography demonstrated minimal influence of either fibrinogen content or cross-linking concentration on the scaffold structure. The specific biological effect of fibrinogen additions into cross-linked collagen are considered by using films as a model for the struts of bulk scaffolds. By considering various additions of fibrinogen to the collagen film with increasing degrees of cross-linking, this study demonstrates a significant biological advantage with fibrinogen addition across the cross-linking concentrations typically applied to collagen-based scaffolds.
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Project description:Heterotopic ossification (HO) is a dynamic, complex pathologic process that often occurs after severe polytrauma trauma, resulting in an abnormal mesenchymal stem cell differentiation leading to ectopic bone growth in soft-tissues including tendons, ligaments, and muscles. The abnormal bone structure and location induce pain and loss of mobility. Recently, we observed that NGF (Nerve growth factor)-responsive TrkA (Tropomyosin receptor kinase A)-expressing nerves invade sites of soft-tissue trauma, and this is a necessary feature for heterotopic bone formation at sites of injury. Here, we assayed the effects of the partial TrkA agonist Gambogic amide (GA) in peritendinous heterotopic bone after extremity trauma. Mice underwent HO induction using the burn/tenotomy model with or without systemic treatment with GA, followed by an examination of the injury site via radiographic imaging, histology, and immunohistochemistry. Single-cell RNA Sequencing confirmed an increase in neurotrophin signaling activity after HO-inducing extremity trauma. Next, TrkA agonism led to injury site hyper-innervation, more brisk expression of cartilage antigens within the injured tendon, and a shift from FGF to TGFβ signaling activity among injury site cells. Nine weeks after injury, this culminated in higher overall levels of heterotopic bone among GA-treated animals. In summary, these studies further link injury site hyper-innervation with increased vascular ingrowth and ultimately heterotopic bone after trauma. In the future, modulation of TrkA signaling may represent a potent means to prevent the trauma-induced heterotopic bone formation and improve tissue regeneration.
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