Author
Francesca Montemurro
Bio: Francesca Montemurro is an academic researcher from University of Pisa. The author has contributed to research in topics: Gelatin & Tissue engineering. The author has an hindex of 11, co-authored 31 publications receiving 639 citations.
Papers
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TL;DR: It is shown that the extracellular matrix protein collagen VI is a key component of the satellite cell niche and establishes a critical role for an extracllular matrix molecule in satellite cell self-renewal and open new venues for therapies of collagen VI-related muscle diseases.
Abstract: Adult muscle stem cells, or satellite cells have essential roles in homeostasis and regeneration of skeletal muscles. Satellite cells are located within a niche that includes myofibers and extracellular matrix. The function of specific extracellular matrix molecules in regulating SCs is poorly understood. Here, we show that the extracellular matrix protein collagen VI is a key component of the satellite cell niche. Lack of collagen VI in Col6a1(-/-) mice causes impaired muscle regeneration and reduced satellite cell self-renewal capability after injury. Collagen VI null muscles display significant decrease of stiffness, which is able to compromise the in vitro and in vivo activity of wild-type satellite cells. When collagen VI is reinstated in vivo by grafting wild-type fibroblasts, the biomechanical properties of Col6a1(-/-) muscles are ameliorated and satellite cell defects rescued. Our findings establish a critical role for an extracellular matrix molecule in satellite cell self-renewal and open new venues for therapies of collagen VI-related muscle diseases.
377 citations
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TL;DR: An in vitro vascularized bone model, using a gelatin-nanohydroxyapatite (gel-nHA) 3D bioprinted scaffold, simulating de novo morphogenesis of capillary vessels occurring during tissue development and highlighting how the inclusion of endothelial cells more realistically supports osteogenesis is highlighted.
Abstract: Bone is a highly vascularized tissue, in which vascularization and mineralization are concurrent processes during skeletal development. Indeed, both components should be included in any reliable and adherent in vitro model platform for the study of bone physiology and pathogenesis of skeletal disorders. To this end, we developed an in vitro vascularized bone model, using a gelatin-nanohydroxyapatite (gel-nHA) three-dimensional (3D) bioprinted scaffold. First, we seeded human mesenchymal stem cells (hMSCs) on the scaffold, which underwent osteogenic differentiation for 2 weeks. Then, we included lentiviral-GFP transfected human umbilical vein endothelial cells (HUVECs) within the 3D bioprinted scaffold macropores to form a capillary-like network during 2 more weeks of culture. We tested three experimental conditions: condition 1, bone constructs with HUVECs cultured in 1:1 osteogenic medium (OM): endothelial medium (EM); condition 2, bone constructs without HUVECs cultured in 1:1 OM:EM; condition 3: bone construct with HUVECs cultured in 1:1 growth medium:EM. All samples resulted in engineered bone matrix. In conditions 1 and 3, HUVECs formed tubular structures within the bone constructs, with the assembly of a complex capillary-like network visible by fluorescence microscopy in the live tissue and histology. CD31 immunostaining confirmed significant vascular lumen formation. Quantitative real-time PCR was used to quantify osteogenic differentiation and endothelial response. Alkaline phosphatase and runt-related transcription factor 2 upregulation confirmed early osteogenic commitment of hMSCs. Even when OM was removed under condition 3, we observed clear osteogenesis, which was notably accompanied by upregulation of osteopontin, vascular endothelial growth factor, and collagen type I. These findings indicate that we have successfully realized a bone model with robust vascularization in just 4 weeks of culture and we highlighted how the inclusion of endothelial cells more realistically supports osteogenesis. The approach reported here resulted in a biologically inspired in vitro model of bone vascularization, simulating de novo morphogenesis of capillary vessels occurring during tissue development.
71 citations
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TL;DR: The results show the great potential of using pectin crosslinked with GPTMS as biomaterial ink to fabricate patient specific scaffolds, which could be used to promote tissue regeneration in vivo.
48 citations
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TL;DR: Ciliogenesis in culture allowed the diagnosis of PCD in four of these patients, it was indicative of a secondary defect in two subjects, and it was not helpful in the remaining three patients, nevertheless it may offer diagnostic help in doubtful cases ofPCD.
Abstract: Background: The diagnosis of primary ciliary dyskinesia (PCD) can be challenging, and it may be particularly difficult to distinguish primary ciliary disease from the secondary changes after infections. Objectives: The purpose of the study was to evaluate if nasal epithelial cells, obtained with nasal brushing instead of a biopsy, could be used in a culture system for the diagnosis of PCD in difficult cases. Methods and main results: Ciliary motion analysis (CMA) and transmission electron microscopy (TEM) were performed on 59 subjects with persistent or recurrent pneumonia. These investigations allowed the diagnosis of PCD in 13 (22%) patients while the defect of the cilia was considered secondary to infections in 37 (63%) subjects. In the remaining nine (15%) patients the diagnostic evaluation with CMA and TEM remained inconclusive. Ciliogenesis in culture allowed the diagnosis of PCD in four of these patients, it was indicative of a secondary defect in two subjects, and it was not helpful in the remaining three patients. Conclusions: Culture of cells obtained with brushing of the nasal turbinate is not a perfect test, nevertheless it may offer diagnostic help in doubtful cases of PCD.
41 citations
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TL;DR: Bone TE uses a scaffold either to induce bone formation from surrounding tissue or to act as a carrier or template for implanted bone cells or other agents, and develops discrete functionally graded scaffolds (discrete FGSs) in order to mimic the graded structure of bone tissue.
40 citations
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TL;DR: Engineered biomaterials able to mimic the in vivo characteristics of stem cell niche provide suitable in vitro tools for dissecting the different roles exerted by the ECM and its molecular components on stem cell behavior.
1,022 citations
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TL;DR: An overview of the design of ideal biomimetic porous scaffolds for bone tissue engineering is presented, and concepts and techniques including the production of a hierarchical structure on both the macro- and nano-scales, the adjustment of biomechanical properties through structural alignment and chemical components, and the control of the biodegradability of the scaffold and its by-products are discussed.
Abstract: Increased use of reconstruction procedures in orthopedics, due to trauma, tumor, deformity, degeneration and an aging population, has caused a blossom, not only in surgical advancement, but also in the development of bone implants. Traditional synthetic porous scaffolds are made of metals, polymers, ceramics or even composite biomaterials, in which the design does not consider the native structure and properties of cells and natural tissues. Thus, these synthetic scaffolds often poorly integrate with the cells and surrounding host tissue, thereby resulting in unsatisfactory surgical outcomes due to poor corrosion and wear, mechanical mismatch, unamiable surface environment, and other unfavorable properties. Musculoskeletal tissue reconstruction is the ultimate objective in orthopedic surgery. This objective can be achieved by (i) prosthesis or fixation device implantation, and (ii) tissue engineered bone scaffolds. These devices focus on the design of implants, regardless of the choice of new biomaterials. Indeed, metallic materials, e.g. 316L stainless steel, titanium alloys and cobalt chromium alloys, are predominantly used in bone surgeries, especially in the load-bearing zone of prostheses. The engineered scaffolds take biodegradability, cell biology, biomolecules and material mechanical properties into account, in which these features are ideally suited for bone tissue repair and regeneration. Therefore, the design of the scaffold is extremely important to the success of clinical outcomes in musculoskeletal surgeries. The ideal scaffolds should mimic the natural extracellular matrix (ECM) as much as possible, since the ECM found in natural tissues supports cell attachment, proliferation, and differentiation, indicating that scaffolds should consist of appropriate biochemistry and nano/micro-scale surface topographies, in order to formulate favorable binding sites to actively regulate and control cell and tissue behavior, while interacting with host cells. In addition, scaffolds should also possess a similar macro structure to what is found in natural bone. This feature may provide space for the growth of cells and new tissues, as well as for the carriers of growth factors. Another important concern is the mechanical properties of scaffolds. It has been reported that the mechanical features can significantly influence the osteointegration between implants and surrounding tissues, as well as cell behaviors. Since natural bone exhibits super-elastic biomechanical properties with a Young's modulus value in the range of 1–27 GPa, the ideal scaffolds should mimic strength, stiffness and mechanical behavior, so as to avoid possible post-operation stress shielding effects, which induce bone resorption and consequent implant failure. In addition, the rate of degradation and the by-products of biodegradable materials are also critical in the role of bone regeneration. Indeed, the mechanical integrity of a scaffold will be significantly reduced if the degradation rate is rapid, thereby resulting in a pre-matured collapse of the scaffold before the tissue is regenerated. Another concern is that the by-products upon degradation may alter the tissue microenvironment and then challenge the biocompatibility of the scaffold and the subsequent tissue repair. Therefore, these two factors should be carefully considered when designing new biomaterials for tissue regeneration. To address the aforementioned questions, an overview of the design of ideal biomimetic porous scaffolds is presented in this paper. Hence, a number of original engineering processes and techniques, including the production of a hierarchical structure on both the macro- and nano-scales, the adjustment of biomechanical properties through structural alignment and chemical components, the control of the biodegradability of the scaffold and its by-products, the change of biomimetic surface properties by altering interfacial chemistry, and micro- and nano-topographies will be discussed. In general, the concepts and techniques mentioned above provide insights into designing superior biomimetic scaffolds for bone tissue engineering.
786 citations
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TL;DR: An exploration of the structural, mechanical, biochemical and biological information present in native human tissue for bioengineering applications is focused on to provide inspiration for the design of future biomaterials.
754 citations
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TL;DR: In this article, the current state of wound healing and wound management products, with emphasis on the demand for more advanced forms of wound therapy and some of the current challenges and driving forces behind this demand, are reviewed.
580 citations
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TL;DR: This review encapsulates where recent advances appear to leave the ever-shifting state of the art in the cell microenvironment, and it highlights areas in which substantial potential and uncertainty remain.
Abstract: The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell–microenvironment interactions continue to overturn much earl...
541 citations