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Wound healing is facilitated by biomaterials-based grafts and substantially impacted by orchestrated inflammatory responses that are essential to the normal repair process. Tropoelastin (TE) based materials are known to shorten the period for wound repair but the mechanism of anti-inflammatory performance is not known. To explore this, we compared the performance of the gold standard Integra Dermal Regeneration Template (Integra), polyglycerol sebacate (PGS), and TE blended with PGS, in a murine full-thickness cutaneous wound healing study. Systemically, blending with TE favorably increased the F4/80+ macrophage population by day 7 in the spleen and contemporaneously induced elevated plasma levels of anti-inflammatory IL-10. In contrast, the PGS graft without TE prompted prolonged inflammation, as evidenced by splenomegaly and greater splenic granulocyte and monocyte fractions at day 14. Locally, the inclusion of TE in the graft led to increased anti-inflammatory M2 macrophages and CD4+ T cells at the wound site, and a rise in Foxp3+ regulatory T cells in the wound bed by day 7. We conclude that the TE-incorporated skin graft delivers a pro-healing environment by modulating systemic and local tissue responses. Tropoelastin (TE) has shown significant benefits in promoting the repair and regeneration of damaged human tissues. In this study, we show that TE promotes an anti-inflammatory environment that facilitates cutaneous wound healing. In a mouse model, we find that inserting a TE-containing material into a full-thickness wound results in defined, pro-healing local and systemic tissue responses. These findings advance our understanding of TE's restorative value in tissue engineering and regenerative medicine, and pave the way for clinical applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Elastin is a key elastomeric protein responsible for the elasticity of many organs, including heart, skin, and blood vessels. Due to its intrinsic long life and low turnover rate, damage in elastin induced by pathophysiological conditions, such as hypercalcemia and hyperglycemia, accumulates during biological aging and in aging-associated diseases, such as diabetes mellitus and atherosclerosis. Prior studies have shown that calcification induced by hypercalcemia deteriorates the function of aortic tissues. Glycation of elastin is triggered by hyperglycemia and associated with elastic tissue damage and loss of mechanical functions via the accumulation of advanced glycation end products. To evaluate the effects on elastin's structural conformations and elasticity by hypercalcemia and hyperglycemia at the molecular scale, we perform classical atomistic and steered molecular dynamics simulations on tropoelastin, the soluble precursor of elastin, under different conditions. We characterize the interaction sites of glucose and calcium and associated structural conformational changes. Additionally, we find that elevated levels of calcium ions and glucose hinder the extensibility of tropoelastin by rearranging structural domains and altering hydrogen bonding patterns, respectively. Overall, our investigation helps to reveal the behavior of tropoelastin and the biomechanics of elastin biomaterials in these physiological environments. Elastin is a key component of elastic fibers which endow many important tissues and organs, from arteries and veins, to skin and heart, with strength and elasticity. During aging and aging-associated diseases, such as diabetes mellitus and atherosclerosis, physicochemical stressors, including hypercalcemia and hyperglycemia, induce accumulated irreversible damage in elastin, and consequently alter mechanical function. Yet, molecular mechanisms associated with these processes are still poorly understood. Here, we present the first study on how these changes in elastin structure and extensibility are induced by hypercalcemia and hyperglycemia at the molecular scale, revealing the essential roles that calcium and glucose play in triggering structural alterations and mechanical stiffness. Our findings yield critical insights into the first steps of hypercalcemia- and hyperglycemia-mediated aging. [Display omitted] [ABSTRACT FROM AUTHOR]

Recreating the cell niche of virtually all tissues requires composite materials fabricated from multiple extracellular matrix (ECM) macromolecules. Due to their wide tissue distribution, physical attributes and purity, collagen, and more recently, tropoelastin, represent two appealing ECM components for biomaterials development. Here we blend tropoelastin and collagen, harnessing the cell-modulatory properties of each biomolecule. Tropoelastin was stably co-blended into collagen biomaterials and was retained after EDC-crosslinking. We found that human dermal fibroblasts (HDF), rat glial cells (Rugli) and HT1080 fibrosarcoma cells ligate to tropoelastin via EDTA-sensitive and EDTA-insensitive receptors or do not ligate with tropoelastin, respectively. These differing elastin-binding properties allowed us to probe the cellular response to the tropoelastin-collagen composites assigning specific bioactivity to the collagen and tropoelastin component of the composite material. Tropoelastin addition to collagen increased total Rugli cell adhesion, spreading and proliferation. This persisted with EDC-crosslinking of the tropoelastin-collagen composite. Tropoelastin addition did not affect total HDF and HT1080 cell adhesion; however, it increased the contribution of cation-independent adhesion, without affecting the cell morphology or, for HT1080 cells, proliferation. Instead, EDC-crosslinking dictated the HDF and HT1080 cellular response. These data show that a tropoelastin component dominates the response of cells that possess non-integrin based tropoelastin receptors. EDC modification of the collagen component directs cell function when non-integrin tropoelastin receptors are not crucial for cell activity. Using this approach, we have assigned the biological contribution of each component of tropoelastin-collagen composites, allowing informed biomaterial design for directed cell function via more physiologically relevant mechanisms. Biomaterials fabricated from multiple extracellular matrix (ECM) macromolecules are required to fully recreate the native tissue niche where each ECM macromolecule engages with a specific repertoire of cell-surface receptors. Here we investigate combining tropoelastin with collagen as they interact with cells via different receptors. We identified specific cell lines, which associate with tropoelastin via distinct classes of cell-surface receptor. These showed that tropoelastin, when combined with collagen, altered the cell behaviour in a receptor-usage dependent manner. Integrin-mediated tropoelastin interactions influenced cell proliferation and non-integrin receptors influenced cell spreading and proliferation. These data shed light on the interplay between biomaterial macromolecular composition, cell surface receptors and cell behaviour, advancing bespoke materials design and providing functionality to specific cell populations. [Display omitted] [ABSTRACT FROM AUTHOR]

Electrospun yarns offer substantial opportunities for the fabrication of elastic scaffolds for flexible tissue engineering applications. Currently available yarns are predominantly made of synthetic elastic materials. Thus scaffolds made from these yarns typically lack cell signaling cues. This can result in poor integration or even rejection on implantation, which drive demands for a new generation of yarns made from natural biologically compatible materials. Here, we present a new type of cell-attractive, highly twisted protein-based yarns made from blended tropoelastin and silk fibroin. These yarns combine physical and biological benefits by being rendered elastic and bioactive through the incorporation of tropoelastin and strengthened through the presence of silk fibroin. Remarkably, the process delivered multi-meter long yarns of tropoelastin-silk mixture that were conducive to fabrication of meshes on hand-made frames. The resulting hydrated meshes are elastic and cell interactive. Furthermore, subcutaneous implantation of the meshes in mice demonstrates their tolerance and persistence over 8 weeks. This combination of mechanical properties, biocompatibility and processability into diverse shapes and patterns underscores the value of these materials and platform technology for tissue engineering applications. Synthetic yarns are used to fabricate textile materials for various applications such as surgical meshes for hernia repair and pelvic organ prolapse. However, synthetic materials lack the attractive biological and physical cues characteristic of extracellular matrix and there is a demand for materials that can minimize postoperative complications. To address this need, we made yarns from a combination of recombinant human tropoelastin and silk fibroin using a modified electrospinning approach that blended these proteins into functional yarns. Prior to this study, no protein-based yarns using tropoelastin were available for the fabrication of functional textile materials. Multimeter-long, uniform and highly twisted yarns based on these proteins were elastic and cell interactive and demonstrated processing to yield textile fabrics. By using these yarns to weave fabrics, we demonstrate that an elastic human matrix protein blend can deliver a versatile platform technology to make textiles that can be explored for efficacy in tissue repair. [ABSTRACT FROM AUTHOR]

Native elastin is inherently difficult to purify due to its insolubility. As a result, elastin-like polypeptides, recombinant human tropoelastin, and solubilized animal elastin fragments are the focus of elastin-based research. All of these elastin-derivatives possess the ability to self-assemble by coacervation in a temperature-dependent manner. These properties have led to great interest in creating a new class of materials for regenerative medicine including injectable, photo cross-linkable, or thermally responsive hydrogels, elastin fibers that can be combined with other materials, and conjugated to other bioactive components for therapeutic delivery. Elastin is an extracellular matrix protein polymer that imparts tissues with the ability to endure stretch-recoil cycles. The formation of elastin has been explored through its major components, such as the natural precursor tropoelastin and mimics in elastin-like polypeptides, and involves a remarkable process of hierarchical self-assembly at physiological temperatures through interactions principally between their hydrophobic sequences. These properties have made elastin an attractive candidate for incorporation into biomaterials for a range of applications in regenerative medicine. This review summarizes the recent advances in understanding how the sequence and structure of elastin influence the thermodynamics that govern the functionality of elastin and its derivatives, and describes innovations in harnessing these mechanisms to create tunable elastin-based biomaterials. [ABSTRACT FROM AUTHOR]

We demonstrate a novel approach for the production of tunable quantities of elastic fibers. We also show that exogenous tropoelastin is rate-limiting for elastin synthesis regardless of the age of the dermal fibroblast donor. Additionally, we provide a strategy to further enhance synthesis by older cells through the application of conditioned media. We show that this approach delivers an elastin layer on one side of the leading dermal repair template for contact with the deep dermis in order to deliver prefabricated elastic fibers to a physiologically appropriate site during subsequent surgery. This system is attractive because it provides for the first time a viable path for sufficient, histologically detectable levels of patient elastin into full-thickness wound sites that have until now lacked this elastic underlayer. Statement of Significance The scars of full thickness wounds typically lack elasticity. Elastin is essential for skin elasticity and is enriched in the deep dermis. This paper is significant because it shows that: (1) we can generate elastic fibers in tunable quantities, (2) tropoelastin is the rate-limiting component in elastin synthesis in vitro , (3) we can generate elastin fibers regardless of donor age, (4) we describe a novel approach to further increase the numbers and thickness of elastic fibers for older donors, (5) we improve on Integra Dermal Regeneration Template and generate a new hybrid biomaterial intended to subsequently surgically deliver these elastic fibers, (6) the elastic fiber layer is presented on the side of Integra that is intended for delivery into its physiologically appropriate site i.e. the deep dermis. [ABSTRACT FROM AUTHOR]

Neointimal hyperplasia, which results from the activation, proliferation and migration of vascular smooth muscle cells (SMCs), is a detrimental condition for vascular stents or vascular grafts that leads to stenosis. Preventing neointimal hyperplasia of vascular grafts is critically important for the success of arterial vascular grafts. We hypothesized that tropoelastin seeding onto the luminal surface of the graft would prevent neointimal hyperplasia through suppressing neointimal smooth muscle cell proliferation. In this study, we investigated the efficacy of tropoelastin seeding in preventing neointimal hyperplasia of bioresorbable arterial vascular grafts. Poly (glycolic acid) (PGA) fiber mesh coated with poly ( l -lactic-co-ε-caprolactone) (PLCL) scaffolds reinforced by poly ( l -lactic acid) (PLA) nano-fibers were prepared as bioresorbable arterial grafts. Tropoelastin was then seeded onto the luminal surface of the grafts. Tropoelastin significantly reduced the thickness of the intimal layer. This effect was mainly due to a substantial reduction the number of cells that stained positive for SMC (α-SMA) and PCNA in the vessel walls. Mature elastin and collagen type I and III were unchanged with tropoelastin treatment. This study demonstrates that tropoelastin seeding is beneficial in preventing SMC proliferation and neointimal hyperplasia in bioresorbable arterial vascular grafts. Statement of Significance Small resorbable vascular grafts can block due to the over-proliferation of smooth muscle cells in neointimal hyperplasia. We show here that the proliferation of these cells is restricted in this type of graft. This is achieved with a simple dip, non-covalent coating of tropoelastin. It is in principle amendable to other grafts and is therefore an attractive process. This study is particularly significant because: (1) it shows that smooth muscle cell proliferation can be reduced while still accommodating the growth of endothelial cells, (2) small vascular grafts with an internal diameter of less than 1 mm are amenable to this process, and (3) this process works for resorbable grafts. [ABSTRACT FROM AUTHOR]

Peripheral nerve regeneration may be enhanced through the use of biodegradable thin film biomaterials as highly tuned inner nerve conduit liners. Dorsal root ganglion neuron and Schwann cell responses were studied on protein films comprising silk fibroin blended with recombinant human tropoelastin protein. Tropoelastin significantly improved neurite extension and enhanced Schwann cell process length and cell area, while the silk provided a robust biomaterial template. Silk–tropoelastin blends afforded a 2.4-fold increase in neurite extension, when compared to silk films coated with poly- d -lysine. When patterned by drying on grooved polydimethylsiloxane (3.5 μm groove width, 0.5 μm groove depth), these protein blends induced both neurite and Schwann cell process alignment. Neurons were functional as assessed using patch-clamping, and displayed action potentials similar to those cultured on poly(lysine)-coated glass. Taken together, silk–tropoelastin films offer useful biomaterial interfacial platforms for nerve cell control, which can be considered for neurite guidance, disease models for neuropathies and surgical peripheral nerve repairs. [ABSTRACT FROM AUTHOR]

Abstract: Elastin provides structural integrity, biological cues and persistent elasticity to a range of important tissues, including the vasculature and lungs. Its critical importance to normal physiology makes it a desirable component of biomaterials that seek to repair or replace these tissues. The recent availability of large quantities of the highly purified elastin monomer, tropoelastin, has allowed for a thorough characterization of the mechanical and biological mechanisms underpinning the benefits of mature elastin. While tropoelastin is a flexible molecule, a combination of optical and structural analyses has defined key regions of the molecule that directly contribute to the elastomeric properties and control the cell interactions of the protein. Insights into the structure and behavior of tropoelastin have translated into increasingly sophisticated elastin-like biomaterials, evolving from classically manufactured hydrogels and fibers to new forms, stabilized in the absence of incorporated cross-linkers. Tropoelastin is also compatible with synthetic and natural co-polymers, expanding the applications of its potential use beyond traditional elastin-rich tissues and facilitating finer control of biomaterial properties and the design of next-generation tailored bioactive materials. [Copyright &y& Elsevier]

Abstract: We present an electrospun synthetic human elastin:collagen composite scaffold aimed at dermal tissue engineering. The panel of electrospun human tropoelastin and ovine type I collagen blends comprised 80% tropoelastin+20% collagen, 60% tropoelastin+40% collagen and 50% tropoelastin+50% collagen. Electrospinning efficiency decreased with increasing collagen content under the conditions used. Physical and mechanical characterization encompassed fiber morphology, porosity, pore size and modulus, which were prioritized to identify the optimal candidate for dermal tissue regeneration. Scaffolds containing 80% tropoelastin and 20% collagen (80T20C) were selected on this basis for further cell interaction and animal implantation studies. 80T20C enhanced proliferation and migration rates of dermal fibroblasts in vitro and were well tolerated in a mouse subcutaneous implantation study where they persisted over 6weeks. The 80T20C scaffolds supported fibroblast infiltration, de novo collagen deposition and new capillary formation. [Copyright &y& Elsevier]

Abstract: The interaction of proteins and cells with polymers is critical to their use in scientific and medical applications. In this study, plasma immersion ion implantation (PIII) was used to modify the surface of the conducting polymer, polypyrrole, which possesses electrical properties. PIII treatment enabled persistent, covalent binding of the cell adhesive protein, tropoelastin, without employing chemical linking molecules. In contrast tropoelastin was readily eluted from the untreated surface. Through this differential persistence of binding, surface bound tropoelastin supported cell adhesion and spreading on the PIII treated but not the untreated polypyrrole surface. The application of a steel shadow mask during PIII treatment allowed for spatial definition of tropoelastin exclusively to PIII treated regions. The general applicability of this approach to other extracellular matrix proteins was illustrated using collagen I, which displayed similar results to tropoelastin but required extended washing conditions. This approach allowed fine patterning of cell adhesion and spreading to tropoelastin and collagen, specifically on PIII treated polypyrrole regions. We therefore present a methodology to alter the functionality of polypyrrole surfaces, generating surfaces that can spatially control cellular interactions through protein functionalization with the potential for electrical stimulation. [Copyright &y& Elsevier]

Abstract: Small-diameter synthetic vascular graft materials fail to match the patency of human tissue conduits used in vascular bypass surgery. The foreign surface retards endothelialization and is highly thrombogenic, while the mismatch in mechanical properties induces intimal hyperplasia. Using recombinant human tropoelastin, we have developed a synthetic vascular conduit for small-diameter applications. We show that tropoelastin enhances endothelial cell attachment (threefold vs. control) and proliferation by 54.7±1.1% (3days vs. control). Tropoelastin, when presented as a monomer and when cross-linked into synthetic elastin for biomaterials applications, had low thrombogenicity. Activation of the intrinsic pathway of coagulation, measured by plasma clotting time, was reduced for tropoelastin (60.4±8.2% vs. control). Platelet attachment was also reduced compared to collagen. Reductions in platelet interactions were mirrored on cross-linked synthetic elastin scaffolds. Tropoelastin was subsequently incorporated into a synthetic elastin/polycaprolactone conduit with mechanical properties optimized to mimic the human internal mammary artery, including permeability, compliance, elastic modulus and burst pressure. Further, this multilayered conduit presented a synthetic elastin internal lamina to circulating blood and demonstrated suturability and mechanical durability in a small scale rabbit carotid interposition model. [ABSTRACT FROM AUTHOR]

Abstract: Elastin is a key extracellular matrix protein in a range of tissues and a viable candidate for elastic tissue engineering. Elastin is not typically incorporated into engineered scaffolds because of lack of access to pure, homogeneous human elastin. Recombinant human tropoelastin, the monomer precursor of elastin, can be chemically cross-linked to form a polymer and used to generate biomaterials with physical properties similar to native elastin. In this study, we use electrospinning to generate versatile tropoelastin microfibers. Tropoelastin retained structural and biological properties, including secondary structure and coacervation temperature, after fiber formation but was solubilized on exposure to an aqueous environment prior to cross-linking. Two cross-linking methods were utilized to generate synthetic elastin microfibers that were stable in aqueous environments. Microfibers stably persisted for up to 180days at 37°C. Three primary human cell types derived from elastic tissues were assessed and found to attach and proliferate on both types of microfibers. [Copyright &y& Elsevier]

Abstract: Polymers are used for the fabrication of many prosthetic implants. It is desirable for these polymers to promote biological function by promoting the adhesion, differentiation and viability of cells. Here we have used plasma immersion ion implantation (PIII) treatment of polystyrene to modify the polymer surface, and so modulate the binding of the extracellular matrix protein tropoelastin. PIII treated, but not untreated polystyrene, bound tropoelastin in a sodium dodecyl sulfate (SDS)-resistant manner, consistent with previous enzyme-binding data that demonstrated the capability of these surfaces to covalently attach proteins without employing chemical linking molecules. Furthermore sulfo-NHS acetate (SNA) blocking of tropoelastin lysine side chains eliminated the SDS-resistant binding of tropoelastin to PIII-treated polystyrene. This implies tropoelastin is covalently attached to the PIII-treated surface via its lysine side chains. Cell spreading was only observed on tropoelastin coated, PIII-treated polystyrene surfaces, indicating that tropoelastin was more biologically active on the PIII-treated surface compared to the untreated surface. A contact mask was used to pattern the PIII treatment. Following tropoelastin attachment, cells spread preferentially on the PIII-treated sections of the polystyrene surface. This demonstrates that PIII treatment of polystyrene improves the polymer’s tropoelastin binding properties, with advantages for tissue engineering and prosthetic design. [Copyright &y& Elsevier]

Abstract: Tropoelastin is a 60–72kDa alternatively spliced extracellular matrix protein and a key component of elastic fibres. It is found in all vertebrates except for cyclostomes. Secreted tropoelastin is tethered to the cell surface, where it aggregates into organised spheres for cross-linking and incorporation into growing elastic fibres. Tropoelastin is characterised by alternating hydrophobic and hydrophilic domains and is highly flexible. The conserved C-terminus is an area of the molecule of particular biological importance in that it is required for both incorporation into elastin and for cellular interactions. Mature cross-linked tropoelastin gives elastin, which confers resilience and elasticity on a diverse range of tissues. Elastin gene disruptions in disease states and knockout mice emphasise the importance of proper tropoelastin production and assembly, particularly in vascular tissue. Tropoelastin constructs hold promise as biomaterials as they mimic many of elastin''s physical and biological properties with the capacity to replace damaged elastin-rich tissue. [Copyright &y& Elsevier]

Abstract: Elastin is a key structural component of the extracellular matrix. Tropoelastin is the soluble precursor of elastin. In addition to providing elastic recoil to various tissues such as the aorta and lung, elastin, tropoelastin and elastin degradation products are able to influence cell function and promote cellular responses. These responses include chemotaxis, proliferation and cell adhesion. The interaction of elastin products with cells has been attributed to the elastin receptor. However, additional cell-surface receptors have also been identified. These include G protein-coupled receptors and integrins. The potential roles of these receptors in cell–elastin interactions, with particular focus on elastin formation are discussed. [Copyright &y& Elsevier]

Tropoelastin is the soluble precursor of the essential resilient connective tissue protein elastin. We examined the binding of integrin αvβ3 to tropoelastin. In quantitative colorimetric solid-phase assays, purified αvβ3 demonstrated saturable, divalent cation-dependent, single-site binding behavior on tropoelastin with a dissociation constant of 3.8 ± 0.9 nM in the presence of 1 mM Mn2+ which increased to 23 ± 5 nM in the presence of 1 mM Ca2+. Association with αvβ3 was localized to the C-terminal 16 residues of tropoelastin, encompassing the region encoded by exon 36. This region comprises a unique disulfide loop in tropoelastin that is not essential for the interaction. This is the first identification of a specific, single binding site on tropoelastin and the first observation of direct binding of an integrin to a tropoelastin domain. [Copyright &y& Elsevier]

• Intact elastin is required for normal lung function. • High-resolution ECM visualization assists in elastin imaging. • Improved lung imaging and modeling enhance ECM visualization. • Better knowledge of the spatial distribution of elastin in lung disease is needed. Elastic fibers are an essential part of the pulmonary extracellular matrix (ECM). Intact elastin is required for normal function and its damage contributes profoundly to the etiology and pathology of lung disease. This highlights the need for novel lung-specific imaging methodology that enables high-resolution 3D visualization of the ECM. We consider elastin's involvement in chronic respiratory disease and examine recent methods for imaging and modeling of the lung in the context of advances in lung tissue engineering for research and clinical application. [ABSTRACT FROM AUTHOR]

Wound healing has historically relied on endogenous processes, but engineered materials are increasingly being used to assist tissue repair. Elastin is an essential functional component of the dermal extracellular matrix and is an important part of skin wound repair that encompasses an elastic dermis. Advances in modern technology have better elucidated the specific signaling factors and cells that contribute to the physiological process and have led to new developments in wound care technology. We review elastin-based materials that are used to encourage wound repair. Elastin-related biomaterials, particularly those based on tropoelastin, are particularly promising because tropoelastin is assembled to make elastin. We present insights into the roles of elastin-related biomaterials and their associated in vitro and in vivo benefits on wound healing. Novel elastin-based scaffolds have demonstrated efficacy. Elastin-based skin substitutes improve clinical outcomes in burn wounds when transplanted beneath split-thickness skin grafts. Functionalized elastin recombinamers enhance in vitro endothelial and fibroblast cell proliferation as well as in vivo angiogenesis. Recombinant human tropoelastin promotes early angiogenesis and harmonizes with the therapeutic benefits of existing dermal dressings. Tropoelastin improves wound healing and promotes de novo elastin synthesis. Tropoelastin-based constructs can be polymerized using a range of methods, including photocrosslinking, chemical crosslinking and heat to enhance healing. [ABSTRACT FROM AUTHOR]

Soluble elastin-like peptides (ELPs) can be engineered into a range of physical forms, from hydrogels and scaffolds to fibers and artificial tissues, finding numerous applications in medicine and engineering as “smart polymers”. Elastin-like peptides are attractive candidates as a platform for novel biomaterial design because they exhibit a highly tunable response spectrum, with reversible phase transition capabilities. Here, we report the design of the first virtual library of elastin-like protein models using methods for enhanced sampling to study the effect of peptide chemistry, chain length, and salt concentration on the structural transitions of ELPs, exposing associated molecular mechanisms. We describe the behavior of the local molecular structure under increasing temperatures and the effect of peptide interactions with nearest hydration shell water molecules on peptide mobility and propensity to exhibit structural transitions. Shifts in the magnitude of structural transitions at the single-molecule scale are explained from the perspective of peptide-ion-water interactions in a library of four unique elastin-like peptide systems. Predictions of structural transitions are subsequently validated in experiment. This library is a valuable resource for recombinant protein design and synthesis as it elucidates mechanisms at the single-molecule level, paving a feedback path between simulation and experiment for smart material designs, with applications in biomedicine and diagnostic devices. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have emerged as promising cell-based therapies in the treatment of degenerative and inflammatory conditions. However, despite accumulating evidence of the breadth of MSC functional potency, their broad clinical translation is hampered by inconsistencies in therapeutic efficacy, which is at least partly due to the phenotypic and functional heterogeneity of MSC populations as they progress towards senescence in vitro. MSC senescence, a natural response to aging and stress, gives rise to altered cellular responses and functional decline. This review describes the key regenerative properties of MSCs; summarises the main triggers, mechanisms, and consequences of MSC senescence; and discusses current cellular and extracellular strategies to delay the onset or progression of senescence, or to rejuvenate biological functions lost to senescence. • Mesenchymal stem cells are important therapeutic tools, but face age-related functional decline. • Senescence is induced by exogenous and endogenous stimuli such as oxidative or replicative stress. • Senescence induces phenotypic changes that may be used to identify and isolate aging or aged cells. • Mitigating senescence involves disrupting senescence signalling or capturing niche-like culture conditions. [ABSTRACT FROM AUTHOR]

An abstract of the article "Elastin," by Suzanne M. Mithieux and Anthony S. Weiss is presented.

Elastomers are popular in vascular engineering applications, as they offer the ability to design implants that match the compliance of native tissue. By mimicking the natural tissue environment, elastic materials are able to integrate within the body to promote repair and avoid the adverse physiological responses seen in rigid alternatives that often disrupt tissue function. The design of elastomers has continued to evolve, moving from a focus on long term implants to temporary resorbable implants that support tissue regeneration. This has been achieved through designing chemistries and processing methodologies that control material behavior and bioactivity, while maintaining biocompatibility in vivo. Here we review the latest developments in synthetic and natural elastomers and their application in cardiovascular treatments. [ABSTRACT FROM AUTHOR]

The elastomeric proteins elastin and resilin have been used extensively in the fabrication of biomaterials for tissue engineering applications due to their unique mechanical and biological properties. Tropoelastin is the soluble monomer component of elastin. Tropoelastin and resilin are both highly elastic with high resilience, substantial extensibility, high durability and low energy loss, which makes them excellent candidates for the fabrication of elastic tissues that demand regular and repetitive movement like the skin, lung, blood vessels, muscles and vocal folds. Combinations of these proteins with silk fibroin further enhance their biomechanical and biological properties leading to a new class of protein alloy materials with versatile properties. In this review, the properties of tropoelastin-based and resilin-based biomaterials with and without silk are described in concert with examples of their applications in tissue engineering. [ABSTRACT FROM AUTHOR]

[Display omitted] • New approaches in bone tissue engineering have been developed. • The generation of synthetic bone tissues reflective of native tissue structure and function presents a frontier challenge. • Prospects for cutting-edge solutions to repair large bone defects are considered. Human bone has a strong regenerative capacity that allows for restoration of its function and structure after damage. For degenerative bone diseases or large defects, bone regeneration requirements exceed the natural potential for self-healing, so bone grafts or bone substitute materials are required to support the regeneration of bone tissue. Compared to the plethora of endogenous bioactive molecules and cells in native bone grafts, the regenerative capacity of tissue-engineered materials is limited. The modest clinical impact of tissue-engineered strategies in this domain can be attributed to a failure to fully recognize key physical and biological events during bone healing, and to recapitulate the structure and composition of the target tissue to generate truly biomimetic grafts. This limitation has motivated the emergence of new strategies such as immunomodulation, endochondral ossification routes, engineered microtissues and hematoma regulation, and the development of advanced biomaterials including gene-activated matrices, soft microgels and hierarchically designed materials. [ABSTRACT FROM AUTHOR]