Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine - Free Essay Example

Sample details Pages: 6 Words: 1784 Downloads: 7 Date added: 2019/06/26 Category Biology Essay Level High school Tags: Stem Cell Essay Did you like this example? Biomaterials for stem cell delivery in cardiovascular regeneration Cardiovascular diseases (CVDs) are disorders of the heart and the blood vessels which are the leading cause of morbidity and mortality worldwide and related with 31% global deaths every year.[64] Although pharmacological and interventional treatments are well-established to relief the symptoms and complications (e.g. arrhythmia) to prevent sudden cardiac death, these strategies mainly delay the death with a poor long-term prognosis rather than provide functional recovery of cardiovascular system.[1b, 65] Due to the limited regenerative capacity of mature caridomyocytes (CMs), stem cell based therapies are considered as one of the most promising treatments to restore the compromised function and regenerate lost tissue for cardiovascular system. Although clinical trials using various types of stem cells such as MSCs,[66] hematopoietic stem cells (HSCs),[67] and bone marrow-derived mononuclear cells (BMMNCs)[68] showed modest improvement in functional recovery of myocardium and blood ve ssels, the effect of cell treatment is still limited due to the low survival and retention of the transplanted cells. Don’t waste time! Our writers will create an original "Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine" essay for you Create order Therefore, development of more efficient delivery strategies for applications of stem cell-based therapies in CVDs treatment is urgently needed. Regenerate the Cardiac Tissue The heart pumps blood with rhythmic contractions to support circulatory system which is crucial for vertebrate life.[69] Most cardiac diseases, such as myocarial infarction (MI), are caused by insufficient supply of oxygen and nutrients occurs during ischemic conditions resulted from blockage of coronary artery. These are fatal and will result in irreversible damage of CMs. Stem cell-based therapies hold great promise of effective treatment to recover cardiac function and attenuate adverse ventricular remodeling. However, there are still many obstacles to regenerate cardiac tissue via stem cell-based therapies including cell survival and maturity, anisotropic structure and alignment of CMs, electromechanical integration of transplanted cells with the native myocardium, and angiogenesis of neonatal cardiac tissue. One of the major hurdles associated with current clinical application of stem cell therapy for cardiac regeneration is the low survival and retention during and after transplantation. To overcome the issues, diverse biomaterials have been developed and utilized in preclinical trails especially for MI treatment. The initial concern was providing mechanical protection to prevent cell necrosis caused by shear and extensional forces during injection process. Polymer- and protein-based shear-thinning hydrogels such as hyaluronic acid shear-thinning hydrogel was shown to be an effective delivery biomaterial to salvage cell viability, thus improve myocardium remodeling and functional recovery.[70] Stimuli-sensitive polymers which are viscoelastic liquid during injection but can be rapid polymerized under physiological conditions also act as an excellent candidate for stem cell delivery in cardiac regeneration.[71] Combination of shear-thing and stimuli-responsive properties can increase the mechanical strength and providing controllable degradation which is critical for cell integration.[47b] Single cell encapsulation represents another major technique for cell protection with advantages of higher encapsulation efficiency and permeability of nutrients compared to conventional hydrogel delivery.[53, 72] A recent research reported by Davis group encapsulated single explant-derived cardiac stem cells (EDCs) in nanoporous gel (NPG) cocoons consist of ECM and low melt agarose with an average diameter around 60 m (Figure 2).[73] The ECM component provided the adhesive site which protected cells through integrin-dependent pro-survival signaling. Meanwhile, incorporation of ECM component promoted cell migration potential which would benefit integration of the delivered cells to the host myocardium. Increasing agarose concentration from 2% to 3.5% in NPG promoted cell survival in short time by reducing cell apoptosis and enhance cell proliferation, which attributed to the incr eased stiffness of the matrix. Although the increased stiffness did not further improve long-term cell retention, it enhanced the exosome production and secretion of cytokines including interleukin-6 (IL-6) and beta fibroblast growth factor (bFGF) from EDCs which play critical roles in post infarct healing.[74] Intramyocardial injection of NPG capsule compositions indicated the importance of matrix stiffness in the cardiac regeneration as the 3.5% NPG-EDCs showed significant decrease in infarct size, and increase in ejection fraction and peri-infarct vessels formation compared to suspended EDCs and 2% NPG-EDCs. Besides the mechanical stress during delivery, the specific local microenvironments of MI region also induce diverse stresses which limited the survival and retention of transplanted cells. The oxidative stress occurred post MI, especially after reperfusion, induces damage of cell membrane and causes cell death.[75] Therefore, biomaterials with antioxidant properties which could reduce reactive oxygen species (ROS) can also improve stem cell survival and cardiac regeneration after delivery. For instance, a recent study from Wang group delivered the brown adipose-derived stem cells (BADSCs) using a fullerenol/ alginate hydrogel for MI treatment.[27] The water soluble fullerenol nanoparticles had great antioxidant property due to the abundance of electron-deficient position which is capable to absorb reactive oxygen species (ROS) and quench the ROS via electron transfer.[76] This antioxidant property promoted cell survival under ROS rich environment. The fullerenol nanoparticles increa sed expression level of phosphorylated ERK and p38 while inhibited expression of phosphor-JNK, which reduced the apoptosis of BADSCs induced by H2O2. Meanwhile, activation of p38-MAPK pathway by fullerenol nanoparticles facilitated the cardiomyogenic differentiation of BADSCs with higher expression of cTnT, ? ±-actinin, and Cx-43 which are cariomyocyte-specific markers. In vivo experiments further proved that the fullerenol/ alginate hydrogel improved survival and retention of BADSCs at the injection site, which contributed to the remodeling of myocardium by reducing infarct size, enhancing ventricular wall thickness of MI zone, and promoting angiogenesis leading to a functional recovery of the MI hearts. Immune responses from host tissue is also a critical point to affect the efficacy of delivered stem cells. Infiltration of immune cells such as macrophages, neutrophils and T-cells will attack transplanted stem cells leading to cell death and granuloma formation.[77] A recent delivery of stem cells using a thermo-responsive nanogel with coploymer of poly(N-isopropylacrylamine-co-acrylic acid) (P(NIPAM-AA)) into immunocompetent mice avoided the elicit of immunoresponse, as the circulating level of pro-inflammatory factors and presence of immune cells including T-cells and macrophages were significantly reduced compared to hCSCs injected with PBS.[78] Besides synthetic polymer, nature polymer were also observed with anti-inflammatory property to salvage transplanted cells. An alginate-chitosan micromatrix (ACM) which could degrade within 3 d after transplantation were used to encapsulate ESC aggregates.[29] The ACM layer minimized the host immune response to the implanted cell aggregat es within short time which allowed the cells to adapt to the MI microenvironment, and avoided the teratoma formation. This strategy enhanced the cell survival and retention after in vivo delivery compare to saline treated, single cells treated, bare cell aggregates treated and ACM treated groups. Another important factor for functional recovery of myocardium hinges on the structure of regenerated cardiac tissue. Native CMs have a cylindrical shape with length approximately 100 m, diameter of 10-25 m, and assemble anisotropically.[79] The key features of native extracellular matrix (ECM) structure need to be taken into account when regenerate cardiac tissue to acquire native tissue equivalent functions. Linear and honeycomb-like geometries have been widely used to mimic the native ECM structures to guide anisotropic alignment of CMs.[80] More advanced strategies allow fabrication of subcellular-structures mimicking native microenvironment in cardiac tissue. For instance, a recent study fabricated a substrate with multiscale topography that replicated from primary human mature CMs to construct the submicrometer structure of myofibrils in CMs (Figure 3).[81] A micropatterned PDMS substrate with a dimension similar to mature human CMs were firstly prepared and seeded with CMs. Wh en majority of CMs expressed mature cardiomyocyte markers, cells were fixed and further used as template for a second PDMS substrate fabrication. The fully micropatterned surfaces inherited the submicrometer topography features of primary CMs and improved the differentiation and maturation of iPSC-CMs. According to another report from Zhang group, translation of cardiac patches with a native-like cardiac ECM architecture further proved the influences of structure on cardiac regeneration in vivo.[82] The multiphoton-excited (MPE) 3D printing were used to fabricate the gelatin scaffolds replicating the size and distribution of ECM (mainly fibronectin) features that mapped from native myocardial tissue of mouse with resolutions of less than 1 m. Human iPSC-derived cardiac linage cells cultured on the 3D printed scaffold showed similar morphology and alignment as the primary CMs, which leading to a stable and robust contraction, calcium transients, and electrical signal propagation amon g the engineered human-induced pluripotent stem cell-derived cardiac muscle patch (hCMP). Transplantation of hCMP improved the remodeling and functional recovery of infarcted myocardium, indicating regulation of engineered cardiac tissue morphogenesis would significantly improve the efficacy of stem cell treatment for ischemic myocardial injury. Electromechanical integration of delivered cells to host tissue is another issue that hindered the application of stem cells therapies in cardiac regeneration. Mismatch of electrical and mechanical support will cause complications including heart failure, diastolic dysfunction and arrhythmias.[83] Association of conductive nanomaterials[84] and conjugation of conductive polymers[85] have been widely used to improve conductivity of biomaterials. Enhanced bioelectrical signal propagation contributes to the differentiation and maturation of stem cell-derived cardiomyocytes, and improves infarcted myocardium recovery. Meanwhile, more and more researches have focused on the influence of the mechanical properties on cell functions. A consensus has emerged that the mechanical properties of the biomaterials are critical to tissue regeneration especially for ischemic heart treatment.[80c, 83a, 86] The native cardiac tissue has anisotropic mechanical properties and dynamic Youngs modulus in sy stole or diastole. The unique mechanical properties can be achieved by designing of microstructured cardiac patch. For instance, a recent research from Stevens group designed a bow-tie shaped cardiac patch based on chitosan-polyaniline complex.[85c] The conductive polyaniline was deposited on a chitosan film which provided mechanical support. The two positive charged component were ionically crosslinked by phytic acid which also acted as dopant.[85b] By designing a bow-tie shape, the auxetic patch showed native tissue comparabled mechanical properties. And in vivo data showed that the cardiac patches attenuated the hypertrophy of the MI hearts. Although the electromechanical properties can be easily achieved, the thoracic surgery for cell delivery to myocardium is considered more invasive which results in additional stresses. However, a recent report from Radisic group invented a flexible shape-memory film which gave a hint on development of novel injectable cardiac patches.[61a] The patch was fabricated using poly(octamethylene maleate (anhydride) citrate) (POMAC) elastomer (Figure 4). The citrate-based biopolymers have excellent anti-oxidant properties[87] and the abundant carboxyl groups can be easily functionalized with conductive properties[85d], which makes it one of the suitable biomaterials for cardiac regeneration. Micropatterning of the POMAC film with a diamond-like design enabled returning of its original shape after folding. This shape-memory property allowed injection of the cardiac patches into heart tissue without any compromise in cell viability. Meanwhile, the anisotropic structure of the patches leaded to different elasticity in longitudinal and transversal directions which mimic the anisotropic elasticity of native heart tissue. Delivery of the ESC-CMs seeded cardiac patch into rat and porcine infarcted cardiac tissue significantly improved the recovery of a functional myocardium.

Understanding Evidence-Based Public Health Strategies Essay

Introduction In this assignment the author is going to be explaining what public health is and describing the key aspects of public health strategies. P1 Public health is all about preventing disease and prolonging life through the use of promotions of services which are provided by the government to ensure the publics health. The NHS is an example of a service which is provided for the public for their health by the government. The official definition of public health is ‘the science and art of preventing disease, prolonging life, and promoting health through the organised efforts of society’ BTEC National Health and Social Care, Book 2, Stretch, B, Whitehouse, B, page115 Most individuals see public health being about disease and illness†¦show more content†¦There are five main key aspects to public health when implementing strategies to improve the health of the public. Monitoring the health status of the public. Monitoring the health status of the public is done through c ollecting data from a variety of sources through doctors, hospitals or sales etc. this data is collected locally and nationally and produced as statistics. This process allows us to notice how the health is of the public and if anything needs implementing due to there being a concern at that present time or if there are patterns and trends which could potentially be a health issue/concern or threats. An example of monitoring the health status of the population both national and local is smoking. The national statistics of the population smoking in the UK is 27% the local area of Leeds statistics of that area of smoking is 30% both Leeds as an area and nationally realised there needs to be something done to reduce the amount of individuals smoking and both have decided to put strategies into place to decrease the amount of smoking to 21% the realisation of theses statistics is that Leeds as an area has a higher statistic then the national statistic of smoking. 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Can Dickens be Considered a Marxist Writer Free Essays

Abstract: This paper considers Dicken’s as a Marxist writer by examining his interest in the stories that lie behind mass-produced objects; in particular it closely considers Dicken’s article entitled ‘Early Workers at Sorting’. Paper: On July 14th, 1877, Dickens published in All the Year Round an article entitled â€Å"Early Workers: At Sorting†. Under this somewhat uninspiring title, Dickens proceeds to describe what can only be identified as a nineteenth-century paper recycling plant, where: ‘(crumpled up, and otherwise deteriorated from prime value) bits of white paper, brown paper, blue paper, other coloured paper; bits of all these papers with the further subdivision of being soft, hard, ruled, written on; bits of that fine foreign â€Å"tissue,† that is mere phantom, yet tough enough, seemingly, to be bishop’s lawn etherealised†¦ bits of cardboard, straw-board, grayish pulpy oatmeal-like board, and the thin woodboard that, when whole, is curved round into band boxes†¦ tufts of wadding; clips of straw-plait; ends of window-rubbers; emptied cotton reels; lengths of tape, binding, gimp, ribbon’[1] and so forth are ‘gathered and re-gathered†¦ used and reuse d’[2] by a collection of ragged but cheerful sorters. We will write a custom essay sample on Can Dickens be Considered a Marxist Writer? or any similar topic only for you Order Now It is not often that we associate the idea of ecological sustainability with the Victorian period – and with good reason, as this era is more frequently remembered for the massive increases in consumption, carbon emissions, and urban development which marked the heyday of the industrial revolution; for its factories, railways, mines, and quaint Dickensian shops stuffed with the excesses of a global imperial economy. A. G. Hill condemns Dickens as the downfall of the novel from social responsibility to sensationalist entertainment (Hill, 1963 : 155); nevertheless, as this little article by Dickens demonstrates, both recycling, and the accompanying awareness of ecological loss, were recognised in the Victorian era and had a part to play in the literary works produced therein. What is perhaps the most important aspect of â€Å"Early Workers at Sorting† is that, as well as being concerned with the re-use and appropriation of waste materials, it is also concerned with the recycling of human experience that accompanies these materials; a process which ensures that: ‘†¦the word â€Å"rubbish† does not exist, since every item under hand is absolutely wanted, and since there are merchants waiting to buy up all, and to pay for all, at proper market price.’[3] It is in this sense that Dickens can be described as a Marxist writer, in the sense suggested by Terry Eagleton in Marxism and Literature (Eagleton, 2006); concerned as he was with the human experience of production, he criticises waste of both material and human resources: It is the science of adjustment, grown to a good height; rising far superior to that lavish waste that fancies itself so wealthy and so generous, and that is always so full of scorn for what it delights to call the meanness of taking care†¦ this – being impossible without combination, without cheap transit and exact knowledge – is one of the results rendered possible by civilisation, is one of the results that renders rich reward to civilisation in return, since, by means of it, material is gathered and re-gathered, is used and re-used, requiring therefore much less real replenishment, and leaving no chance either for that prohibiting price that would follow upon scarcity, or for that famine otherwise inevitable.[4] In addition to demonstrating a clear awareness of the potential for non-sustainability in the (then) newly burgeoning consumerist culture which has become such a cliche of the Victorian era, this passage raises a number of interesting points. In the first place, the reuse of cast-off materials has a clear moral purpose here, which is at odds with consumerist ideals of consumption; Dickens is echoing the fundamentally Marxist view that that the ‘wealthy and generous’ are in fact guilty of ‘lavish waste’, of which the inevitable result will be scarcity and famine, and the alienation of skilled workers. The focus of the article on the ‘little girl[s] of twelve or thirteen years of age’, ‘stained and ragged and utterly unpolished and raw’[5] who are the ‘Early Workers’ of the title, links this piece to the numerous other writings, such as those found in Sketches by Boz, which question the exploitation and miserable living conditions of the poor who occupy the lowest tiers of the consumerist society. Recycling, then, offers support and sustenance to the poor, as well as a chance to sample the pickings of what they could otherwise never afford; materials filter down through the social system and have their particular value for all ranks of society. However, this chance to recycle is also a result of, as well as a benefit to, human civilisation, and one which ‘renders rich reward’ to those who practice it. As the rest of the article makes clear, this reward is bound up with memory, and with the train of associations which each object carries with it, building up a repository of experiences with each new appropriation which binds the object firmly into human tradition. It is this human connection to the processes of production that was so highly valued by Marx, and which both he and Dickens championed in their separate ways. Scraps of wood, for example, are not just scraps of wood, but rather: ‘smashed wooden boxes that have contained toys, scent, chignons, Paris bonnets, and the like; cotton-reels; useless part of broken wooden toys’, all of which bring echoes with them of their previous human owners. Whether in his novels, such as The Old Curiosity Shop, in his journalistic Sketches by Boz, or in h is ghost stories (such as The Queer Chair), Dickens combines an overarching interest in consumerist objects with a fascination for the humans whose stories are concentrated in and told by those objects, be they items of furniture, books, clothes, or buildings. By cataloguing and bringing to life the human histories of mass-produced objects, Dickens seeks – like all good Marxist writers – to fight against the anonymity and disempowerment that consumerism imposes upon workers, returning to them a sense of identity and connection, and illustrating their irreplaceability in society. Word Count: 1,002 Bibliography: Dickens, C. (1877), â€Å"Early Workers: At Sorting†, All the Year Round, July 14th. Eagleton, T. (2006), Marxism and Literaure, London: Taylor and Francis. Hill, A. G. (1963), â€Å"Marxist Aesthetics†, Critical Survey, Vol. 1, No. 3 (AUTUMN), pp. 153-157. [1] Dickens, Charles. â€Å"Early Workers: At Sorting†. All the Year Round, July 14th, 1877. pp. 463-64. [2] Ibid. p. 464. [3] Ibid. p. 464. [4] Ibid. p. 464. [5] Ibid. p. 462. How to cite Can Dickens be Considered a Marxist Writer?, Essay examples