Stem cells respond to nanoscale surface features, with changes in cell growth and differentiation mediated by alterations in cell adhesion. The interaction of nanotopographical features with integrin ...receptors in the cells' focal adhesions alters how the cells adhere to materials surfaces, and defines cell fate through changes in both cell biochemistry and cell morphology. In this Review, we discuss how cell adhesions interact with nanotopography, and we provide insight as to how materials scientists can exploit these interactions to direct stem cell fate and to understand how the behaviour of stem cells in their niche can be controlled. We expect knowledge gained from the study of cell-nanotopography interactions to accelerate the development of next-generation stem cell culture materials and implant interfaces, and to fuel discovery of stem cell therapeutics to support regenerative therapies.
Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. ...However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the
Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity
In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries.
Abstract As materials technology and the field of biomedical engineering advances, the role of cellular mechanisms, in particular adhesive interactions with implantable devices, becomes more relevant ...in both research and clinical practice. A key tenet of medical device design has evolved from the exquisite ability of biological systems to respond to topographical features or chemical stimuli, a process that has led to the development of next-generation biomaterials for a wide variety of clinical disorders. In vitro studies have identified nanoscale features as potent modulators of cellular behavior through the onset of focal adhesion formation. The focus of this review is on the recent developments concerning the role of nanoscale structures on integrin-mediated adhesion and cellular function with an emphasis on the generation of medical constructs with regenerative applications. From the Clinical Editor In this review, recent developments related to the role of nanoscale structures on integrin-mediated adhesion and cellular function is discussed, with an emphasis on regenerative applications.
In biomaterials science, it is nowadays well accepted that improving the biointegration of dental and orthopedic implants with surrounding tissues is a major goal. However, implant surfaces that ...support osteointegration may also favor colonization of bacterial cells. Infection of biomaterials and subsequent biofilm formation can have devastating effects and reduce patient quality of life, representing an emerging concern in healthcare. Conversely, efforts toward inhibiting bacterial colonization may impair biomaterial–tissue integration. Therefore, to improve the long‐term success of medical implants, biomaterial surfaces should ideally discourage the attachment of bacteria without affecting eukaryotic cell functions. However, most current strategies seldom investigate a combined goal. This work reviews recent strategies of surface modification to simultaneously address implant biointegration while mitigating bacterial infections. To this end, two emerging solutions are considered, multifunctional chemical coatings and nanotopographical features.
Incomplete material biointegration and bacterial infection are regarded as the two major causes of implant failure. Multifunctional chemical coatings and nanotopographical features are proposed as emerging solutions to simultaneously improve cell adhesion and prevent bacterial colonization on the biomaterial surface.
Evidence suggests that altered gut microbiota composition may be involved in the development of obesity. Studies using mice made obese with refined high-fat diets have supported this; however, these ...have commonly used chow as a control diet, introducing confounding factors from differences in dietary composition that have a key role in shaping microbiota composition. We compared the effects of feeding a refined high-fat diet with those of feeding either a refined low-fat diet or a chow diet on gut microbiota composition and host physiology. Feeding both refined low- or high-fat diets resulted in large alterations in the gut microbiota composition, intestinal fermentation, and gut morphology, compared to a chow diet. However, body weight, body fat, and glucose intolerance only increased in mice fed the refined high-fat diet. The choice of control diet can dissociate broad changes in microbiota composition from obesity, raising questions about the previously proposed relationship between gut microbiota and obesity.
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•High-fat diet changes in mouse gut microbiota composition due to diet, not obesity•Glucose intolerance in mice linked to high-fat diet, not changes in gut microbiota•Cecal fermentation (energy harvest) decreased, not increased, by high-fat diet•Choice of control diet is vitally important to studies of microbiota composition
Dalby et al. show that high-fat-diet-induced changes in gut microbiota composition and cecal fermentation can be dissociated from obesity and glucose intolerance in mice by using a nutritionally more appropriate control diet. This highlights the importance of the control diet in interpreting microbiota studies.
Cell mechanotransduction is an area of intense research focus. Until now, very limited tools have existed to study how cells respond to changes in the extracellular matrix beyond, for example, ...mechanical deformation studies and twisting cytometry. However, emerging are a range of elastic, viscoelastic and even purely viscous materials that deform and dissipate on cellular length and timescales. This article reviews developments in these materials, typically translating from 2D model surfaces to 3D microenvironments and explores how cells interact with them. Specifically, it focuses on emerging concepts such as the molecular clutch model, how different extracellular matrix proteins engage the clutch under viscoelastic‐stress relaxation conditions, and how mechanotransduction can drive transcriptional control through regulators such as YAP/TAZ.
Extracellular matrices are viscoelastic in nature. However, most of the current understanding about mechanotransduction comes from cell cultures on elastic substrates, where the contribution of viscous interactions is not considered. This review discusses recent advances in the design of materials with controlled viscoelastic properties and the emergence of the crucial role of matrix viscosity in cell mechanotransductive responses.
There is currently an unmet need for the supply of autologous, patient-specific stem cells for regenerative therapies in the clinic. Mesenchymal stem cell differentiation can be driven by the ...material/cell interface suggesting a unique strategy to manipulate stem cells in the absence of complex soluble chemistries or cellular reprogramming. However, so far the derivation and identification of surfaces that allow retention of multipotency of this key regenerative cell type have remained elusive. Adult stem cells spontaneously differentiate in culture, resulting in a rapid diminution of the multipotent cell population and their regenerative capacity. Here we identify a nanostructured surface that retains stem-cell phenotype and maintains stem-cell growth over eight weeks. Furthermore, the study implicates a role for small RNAs in repressing key cell signalling and metabolomic pathways, demonstrating the potential of surfaces as non-invasive tools with which to address the stem cell niche.
Extracellular matrix (ECM)-derived matrices such as Matrigel are used to culture numerous cell types in vitro as they recapitulate ECM properties that support cell growth, organisation, migration and ...differentiation. These ECM-derived matrices contain various growth factors which make them highly bioactive. However, they suffer lot-to-lot variability, undefined composition and lack of controlled physical properties. There is a need to develop rationally designed biomaterials that can also recapitulate ECM roles. Here, we report the development of fibronectin (FN)-based 3D hydrogels of controlled stiffness and degradability that incorporate full-length FN to enable solid-phase presentation of growth factors in a physiological manner. We demonstrate, in vitro and in vivo, the effect of incorporating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) in these hydrogels to enhance angiogenesis and bone regeneration, respectively. These hydrogels represent a step-change in the design of well-defined, reproducible, synthetic microenvironments for 3D cell culture that incorporate growth factors to achieve functional effects.
Nanotopography presents an effective physical approach for biomaterial cell manipulation mediated through material-extracellular matrix interactions. The extracellular matrix that exists in the ...cellular microenvironment is crucial for guiding cell behaviours, such as determination of integrin ligation and interaction with growth factors. These interactions with the extracellular matrix regulate downstream mechanotransductive pathways, such as rearrangements in the cytoskeleton and activation of signal cascades. Protein adsorption onto nanotopography strongly influences the conformation and distribution density of extracellular matrix and, therefore, subsequent cell responses. In this review, we first discuss the interactive mechanisms of protein physical adsorption on nanotopography. Secondly, we summarise advances in creating nanotopographical features to instruct desired cell behaviours. Lastly, we focus on the cellular mechanotransductive pathways initiated by nanotopography. This review provides an overview of the current state-of-the-art designs of nanotopography aiming to provide better biomedical materials for the future.
●A comprehensive overview of nanotopography fabrication, and nanotopography regulates various cell behaviours.●The interactive physical adsorption between nanotopography and extracellular matrix.●Nanotopography initiates the cellular mechanotransductive pathways and downstream signalling cascades.
Engineered living biomaterials Rodrigo-Navarro, Aleixandre; Sankaran, Shrikrishnan; Dalby, Matthew J. ...
Nature reviews. Materials,
12/2021, Letnik:
6, Številka:
12
Journal Article
Recenzirano
Biomaterials have evolved from inert materials that lack interaction with the body to biologically active, instructive materials that host and provide signals to surrounding cells and tissues. ...Engineered living materials contain living cells (responsive function) and polymeric matrices (scaffolding function) and, thus, can be designed as active and response biomaterials. In this Review, we discuss engineered living materials that incorporate microorganisms as the living, bioactive component. Microorganisms can provide complex responses to environmental stimuli, and they can be genetically engineered to allow user control over responses and integration of numerous inputs. The engineered microorganisms can either generate their own matrix, such as in biofilms, or they can be incorporated in matrices using various technologies, such as coating, 3D printing, spinning and microencapsulation. We highlight biomedical applications of such engineered living materials, including biosensing, wound healing, stem-cell-based tissue engineering and drug delivery, and provide an outlook to the challenges and future applications of engineered living materials.Engineered living materials are composed of a matrix that encapsulates living cells, which endow the biomaterial with controllable responses and dynamic functions. This Review discusses the fabrication and biomedical applications of engineered living materials that contain microorganisms as the living, active component.
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