Tissue engineering for skin

Tissue engineering for skin TISSUE ENGINEERING OF THE SKIN (MECH 5510M) LITERATURE REVIEW SID: 200507638 ABSTRACT: This essay is a literature review on the tissue engineering for skin replacement, with regard to the clinical need, approaches various commercially-available products. Skin is undoubtedly crucial in the maintenance of the bodys internal balance also protecting externally. It gets severely compromised in burns, non-healing ulcers, reconstructive surgeries etc. bringing down the patients quality of life drastically. Tissue engineering is a more efficient approach than traditional skin grafting. It is a research area that is forever evolving, where researchers are always working towards one united goal, i.e. to develop in bulk quantities, a skin substitute that can be handled with less care, integrates faster with the bodys natural matrix and costs reasonable. INTRODUCTION: A lot of research has been undertaken in the past to realize that it is possible to generate skin by applying engineering techniques. This is done by growing skin at a faster rate than normal and in an artificial manner4. Skin is the largest most widely spread organ in the human body. Its role is to protect the bodys internal environment from harshness of the external conditions and restrict entry of microbes, by acting as a barrier4. Several situations diseases arise, due to which the skin gets irreparably damaged, thus requiring interventional help in restoring it back to health. Tissue engineering is the application of engineering techniques to develop biological substitutes1. Burns (acute) ulcers (chronic) are the most common conditions which require the replacement of skin. In developing countries (Fig 1)2,3, due to lack of knowledge on safety, a very high number of burns accidents occur every year, and mostly of fatal nature. The fatality is mainly due to pain, infection, loss of body fluids incapability of the body to self-regenerate large amounts of lost skin5. Thus, experimentation in this field was triggered. Many skin diseases, which lead to necrosis, pigmentation problems, also require engineered skin4. CLINICAL NEED FOR SKIN TISSUE ENGINEERING: In most incidents, both the epidermal and dermal layers require replacement. Conventionally, the treatment method involved skin grafting i.e. autologous (self) split-thickness and full-thickness grafting, where healthy skin was taken from other areas of the body and replaced at the injury site. Split-thickness (comprising of the epidermis a part of the dermis) grafting is not a logical method to use, when a large area of the body (>50%) is affected less healthy skin is available. But, it is todays gold standard approach6. Further trauma, due to grafting, can be painful to a patient who is already in a critical state. Also, scar formation post-operatively is another reason for its reduced usage. Full-thickness grafts are suitable to use when the burned area is less than 2% of the total area. These problems could be avoided if skin (of full or partial thickness) were grown artificially and substituted in the place of real skin6. LITERATURE REVIEW: The skin can be broadly divided into two layers i.e. the epidermis dermis. The epidermis is made up of several layers and may/may not consist of extra-cellular matrix (ECM). The layers from surface to deep are: cornified, granular, spinosal and basalar layers. The most commonly found cells here are the keratinocytes melanocytes. The dermis is constituted by GAGs proteins. Within the dermis, fibroblasts are most commonly found8. Several skin substitutes exist for wound coverage in tissue engineering4. It can be broadly divided into temporary and permanent skin substitutes. The table below (Table 1) is a list of all the material options available for skin replacement: Table 1: Temporary and Permanent Skin Substitutes8 Permanent tissue engineering of the skin can be broadly divided into three categories6, 8: Epidermal replacements Generally, using autologous keratinocyte sheets. Replaces only the epidermis, but â€Å"take rates† are very poor, suitable for superficial burn treatment only. Dermal replacements Replaces only the dermal layer. In most cases, it is applied along with an epidermal graft to improve â€Å"take rates†. Dermo-epidermal (bilayer skin) replacements Replaces both the epidermis and dermis. Suitable for full-thickness burns. Skin replacements have two main components i.e. cells and the scaffold. In wound coverage, three types of cells can be used autologous, allogenic or stem cells. Autologous (self) cell usage is the most preferred as it is easily accepted by the patients body does not need incite and anti-immune responses. Allogenic (donor) cells, if used directly can lead to the eventual rejection of the transplant. However, it is used in an acellular fashion, where the donor keratinocytes are removed prior to culturing9. Stem cells have trans-germal pluripotential properties are currently being researched for their poteintial application in skin engineering. Less information is obtained on keratinocyte stem cells. The suggested reason for their longevity is that KSC cycles very slowly and is resistant to mutations8. The type of biodegradable scaffold, either natural or synthetic permits cells to attach onto them and facilitate handling during transplantation6, 9. Rheinwald Green Experiment8: The experiment carried out in 1975 by Rheinwald and Green where human (autologous) keratinocytes were produced in-vitro, proved to be a breakthrough in this field and modified versions of this method are used nowadays. Extracted keratinocytes were allowed to form colonies on a plastic substrate. These colonies expanded to form a sheet. Stratifications arose as the daughter cells, usually at the centre, started multiplying vertically and a 12-cell layer was achieved. To increase the multiplicative capacity of keratinocytes, a feeder layer (comprising murine Swiss 3T3 lethally irradiated fibroblasts) mitogens were introduced to the culture. Epidermal Replacements: A small skin biopsy of the patient is harvested, which is cultured to produce a patch. The full-thickness biopsy of the patients skin is cut finely and enzymes are added to cause disaggregation of the skin into cells. A feeder layer, as mentioned previously, is used to culture these cells in culture flasks. To promote proliferation, epidermal growth factors, enzymes such as insulin, hydrocortisone, cholera-toxin and bovine serum are used. After colonies have been formed, trypsin is added. The KCs are cultured to confluence and later, the sheets are removed from the flasks (using dispase) for use8. The result of this method compared to the split-thickness gold standard is quite poor, as the dermal layer is missing and it depends upon the health of the dermis existing. Also, it is prone to scarring, takes too long, expensive, extremely fragile and has varying â€Å"take† rates6. Dermal Replacements: It was claimed, in 1952, that using only pure epidermal sheets, success would be lesser than compared to those with a dermis10. To accentuate the success of the epidermal transplantation, dermal replacements were constructed. A dermal replacement that covered the affected area with cryoprserved allogenic skin was used minus the epidermal layer was used11, 12. Also, an observation that allogenic keratinocytes elicited more anti-immune response than allogenic fibroblasts, was reported. To reconstruct the dermis, the two-stage Integra application is most widely used now13. This dermis functions as a scaffold for the attachment of keratinocytes and improves vascularization9. Burke et al (1981) developed a dermal replacement, where a collagen sponge was covered with a silastic layer (synthetic). The sponge behaves as a scaffold for the fibroblast cells. This technique was commercialized into a product (Integra Dermal Regeneration Template) 9, 14. A modification to this employed GAGs along with collagen, in the scaffold. Here, a precipitated mixture of bovine collagen fibres and a chondrotin-6-sulfate (GAG from shark cartilage) was freeze dried. This generated a collagen-GAG sponge scaffold, which had a mean pore size. Cross-linkage to strengthen the matrix was done using gluteraldehyde. Finally, the silastic layer was applied. This is available as a product; Integra Artificial Skin (Chamberlain and Yannas, 1999)9, 15. According to Heimbach et al (1988), this is most suitable for burns patients. The concept of using absorbable polymer scaffolds (synthetic) such as polyglactin 910 or polyglycolic acid was the next improvement in dermal replacements. Here, allogenic fibroblasts are enzymatically cultured and this culture is mounted on the polymer scaffold for integration). Due to this, an ECM consisting of collagen, growth factors, GAGs etc. is formed, which stays active even after it is frozen17. This was commercialized as Dermagraft 8, 16. Two-stage dermis application has shown proven results, and now clinical trials are being conducted to examine the applicability of one-stage dermis, such as Matriderm 6. The dermal replacements essentially require an epidermal covering. Dermo-Epidermal Replacements: These are available both as autologous or off-the-shelf products. In autologous DED replacements, both keratinocytes and fibroblasts are harvested from the patient and are added to the collagen-GAG scaffold. Cultivation of this in culture medium is for around four weeks. This is a more permanent solution 6, 18, 19. The first model of todays Apligraf was done by Bell et al (1979)20. DEDs use human keratinocytes fibroblast cells (allogenic) within a scaffold. Morphological studies after using Apligraf reported the presence of a well-defined epidermis, with all four layers, as in the natural skin, and seeded allogenic fibroblasts aligned in a normal manner within the collagen matrix 8, 21. COMMERCIALLY AVAILABLE PRODUCTS: CONCLUSION FUTURE AIMS: Tissue engineering of the skin was the first to be approved by the FDA has evolved a great deal, from the first application of only cultured keratinocytes to the use of biological skin substitutes. Research is still in-progress to develop skin in bulk quantities, mainly for burns patients, and to mimic all the mechanical and properties and functions of the natural skin. The state of the art results can be achieved now by using cultured keratinocyte cells with the dermal replacement, Integra, in full-thickness, small and clean wounds. This has shown optimal results in cosmesis and wound closure8. However, this branch of tissue engineering is still very much in a developing level. Studies to analyse how to reduce various risks in patients, who receive donor cells should be done. Also, a main difficulty is in getting the cells to attach to the dermis, post-transplantation. Burns patients are highly susceptible to various problems, thus there is a need for materials that present lower risk than animal/human materials. Mainly, it is ideal if the graft starts to behave like natural skin soon after grafting, which is possible only with rapid vascularization and cell implantation. Also, low expense of these products is extremely desirable. REFERENCES: Nerem R M. 1992. Tissue engineering in the USA. Medical Biological Engineering Computing, Vol 30, pp. CE8-CE 12. Burn Incidence and Treatment in the United States: 1999 Fact Sheet (The Burn Foundation, Philadelphia, 1999). Rose, J. K. Herndon, D. N. Advances in the treatment of burn patients. Burns 23 (suppl. 1), S19-S26 (1997). McNeil S. 2007. Progress and opportunities for tissue-engineered skin. Nature. Vol 445 (22), pp. 874-880. Pomahac B, T. Svensjà ¶, F. Yao, H. Brown and E. Eriksson. 1998. Critical Reviews in Oral Bioogy and Medicine. Vol9; pp. 333-344. Bottcher-Haberzeth S, T Bedermann, E Reichmann. 2009. Tissue engineering of skin. Burns, doi:10.1016/j.burns.2009.08.016 Burn Injury Occurrence is higher in Developing Countries. Available from: http://en.wikipedia.org/wiki/Burn Price R, E Anthony, S Myers and H Navsaria. Chapter 17: Tissue engineering for Skin Transplantation. In: Clemens van Blitterswijk, Peter Thomsen, Anders Lindahl, Jeffrey Hubbell, David F. Williams, Ranieri Cancedda, Joost D. de Bruijn and Jà ©rà ´me Sohier eds., Tissue Engineering. Elsevier Inc, Pp. 507-532. Morgan J R, R L Sheridian, R G Tompkins, M L Yarmush and J F Burke. 2004. Chapter 7: Applications of Materials in Medicine, Biology and Artificial Organs (7.12). In: B D Ratner, A S Hoffman, F J Schoen and J E Lemons eds., Biomaterials Science. Elsevier Academic Press, pp. 602-614. Billingham, R.E. and Reynolds, J. 1952. Transplantation studies on sheets of pure epidermal epithelium and on epidermal cell suspensions. British Journal of Plastic Surgery, Vol 5, pp. 25 36. Cuono , C.B. , Langdon , R. , e t al. 1987. Composite autologous-allogeneic skin replacement: development and clinical application. Plastic Reconstruction Surgery, Vol 80, pp 626 637. Heck , E.L. , Bergstresser , P.R. , e t al. 1985. Composite skin graft: frozen dermal allografts support the engraftment and expansion of autologous epidermis . Journal of Trauma, Vol 25, pp. 106 112. Heimbach, D .M., W arden, G .D., e t al. ( 2003 ). Multicenter postapproval clinical trial of Integra dermal regeneration template for burn treatment. Journal of Burn Care Rehabilitation, Vol 24, pp. 42 48 . Burke, J.F. , Yannas , I.V. , e t al. ( 1981 b ). Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury. Annals of Surgery, Vol 194, pp. 413 428. Chamberlain L J, Yannas I V. 1999. Preparation of collagen-glycosaminoglycan copolymers for tissue regeneration. In Methods in Tissue Engineering, J R Morgan and M L Yarmush eds. Humana Press, pp. 3-17. Hansbrough, J.F. , Cooper , M.L., et al. 1992a. Evaluation of a biodegradable matrix containing cultured human fibroblasts as a dermal replacement beneath meshed skin grafts on athymic mice. Surgery, Vol. 111, pp. 438 446. Cooper , M.L. , Hansbrough , J.F. , e t al. 1991. In vivo optimization of a living dermal substitute employing cultured human fibroblasts on a biodegradable polyglycolic acid or polyglactin mesh. Biomaterials, Vol. 12, pp. 243 248. Pham C, Greenwood J, Cleland H, Woodruff P, Maddern G. 2007. Bioengineered skin substitutes for the management of burns: a systematic review. Burns; Vol. 33, pp. 946-57. Boyce ST. 2001 Design principles for composition and performance of cultured skin substitutes. Burns; Vol. 27, pp. 523-33. Bell , E. , Ivarsson , B. , e t al. 1979. Production of a tissue like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proceedings of the National Academy of Science, Vol. 76, pp. 1274 1278. Parenteau , N.L. , Bilbo , P. , et al. 1992. The organotypic culture of human skin keratinocytes and fibroblasts to achieve form and function. Cytotechnology, Vol. 9, pp. 163 171. Apligraf Structure vs. Skin Structure. Available from: http://www.organogenesis.com/images/apligraf_main3.jpg Fig. 3, Collagen GAG scaffolds for Tissue Engineering. Pek et al, 2004, Biomaterials. Available from: http://web.mit.edu/dmse/csg/Tissue_Regeneration.html Fig. 3, Collagen GAG scaffolds for Tissue Engineering. OBrien et al, 2004, Biomaterials. Available from:http://web.mit.edu/dmse/csg/Tissue_Regeneration.html

Analyze the Ways in “Jeffersonian Democracy”

During Jefferson’s Presidency two things changed â€Å"Jeffersonian Democracy†, the War of 1812 contributed because until the war hawks and a growing desire to obtain Florida and Canada Jefferson did not want to get involved in war with Europe, and the Louisiana Purchase also changed his views because he was very Constitutional and when the treaty for the Louisiana Purchase was presented it was argued to be Constitutional. Americans in the South wanted to gain Florida and the people in the North wanted Canada. Jefferson didn’t want to just invade and capture these territories.With the attacks from Natives across the Florida border in the South and the issue of impressment it was hard not to go to war. Jefferson did not want to go to war with Great Britain. A group called the war hawks was born, men who were eager to go to war and get territory. After persuading Jefferson agreed to go to war with Great Britain, and because Spain and Britain were allies they could claim Florida as well. The reason this changed his democracy is he did not want to go to war with European nations, or at all I believe, but he gave in and went to war anyway because of pressure from the war hawks.Another factor in the changing of Jeffersonian Democracy was the Louisiana Purchase. Robert Livingston and James Monroe were sent to France to discuss a treaty with Napoleon. When they returned they had purchased the Louisiana Territory form Napoleon. Jefferson was both pleased and embarrassed. He was glad to have the territory, but being constitutional as he was, he was not sure it was Constitutional, until his advisors assured him that it fell under his ability to make treaties.This changed his view because it had changed him to be less strict constitutionally and he was already exploring the territory (and beyond) before the treaty was already made. Jefferson went through a lot of events that changed his view of Democracy and how he ran the nation, but two big ones were the War of 1812, because he went to war even though he personally didn’t want to, and the Louisiana Purchase, because of his belief that the Federal government only had powers expressed in the Constitution.

Motivation, Satisfaction, and Performance

Motivation, Satisfaction and Performance Plan LDR 531 Table of Contents The Team1 Motivation, Satisfaction, and Performance1 Motivation1 Satisfaction2 Performance2 The Plan2 References4 The Team The team is composed of four team members and one team manager; Mike, James, Mary, Katy and Barb. The team does a good job staying motivated and satisfied, and also performs well. However, there are moments the team struggles due to differences in attitudes, emotions, and values. The team manager strives to implement ways to keep the team where it should be.The plan will address the ways to keep the team motivated, satisfied and preforming well. Motivation, Satisfaction, and Performance The team currently has one thing that motivates them, satisfies them, and keeps them performing well, bonuses. The team works on different projects throughout the year. Meeting the deadlines on these projects keeps the team performing well which in turn earns them a bigger bonus check which motivates and satis fies them. However, there have been several instances where the team has not met a deadline and it has caused them their bonus for the project.This then causes issues between the team members and keeps them from performing well, being satisfied, and being motivated. Motivation In order to increase team motivation, the manager has come up with two suggestions; get connected and show the team appreciation. The best way to get connected with your team is to build relationships with them. It is very important to let your team know you have their best interest in mind. By doing so, you also build trust. Very rarely do employees do more than just the minimum when they do not feel like you will do more for them. The key here is to establish a professional relationship, not a friendship.By establishing these relationships and getting connected with your team, you will increase their motivation. (Kearns, 2010) Showing the team appreciation is also something that will increase the motivation within a team. Doing simple gestures like bringing in donuts or bagels (something your team enjoys), shows you are thinking of them and appreciate their hard work. It is important that when deciding to do this, it is not overdone. Team members can start to expect such a gesture and you don’t want that happening. Satisfaction The team has expressed major dissatisfaction when it comes to working long days for several weeks at a time.In order to overcome this dissatisfaction, the team manager has proposed the team take turns in deciding a schedule for the week. There are several rules that need to be taken into account, like hours of operation. By implementing this type of plan, the employees will be allowed to work out schedules that satisfy all of them and they get a sense of more than just work back. (Improve Your Employees' Job Satisfaction, 2004) Performance The most important thing to increase performance is to give regular performance reviews. This ensures that the team m embers and the team manager are all on the same page.While in a team, it’s important to discuss team reviews as well. As a manager, it is important to do this so that the team as a whole knows how they are doing. It allows for corrections and for the team to know how well they are doing. Strengths are a great focus point, however it is also important to address the weaknesses so they can be corrected. (McCormick, 2012) The Plan The following is a detail of what the plan is for motivation, satisfaction, and performance. Months 1-3 * Inform team members of the plan * 1st individual and team performance reviews * Set expectations Start developing a professional relationship * Set expectations * Team manager only: Treat the team (bagels, donuts, etc. ) * Set schedule * Discuss rules for schedules during long projects * Set expectations Months 4-6 * 2nd individual and performance reviews * Evaluate schedule setting for long projects * Evaluate professional relationships Months 7-1 2 * 3rd and 4th individual and performance reviews * Schedule setting for long projects * Continue building professional relationships At the end of the year, there will be a yearly evaluation taking into account all the evaluations for the year.It is a good way to show your team how far they’ve come. At this time, any changes that the team believes should be made can be addressed. References Improve Your Employees' Job Satisfaction. (2004, March 22). Retrieved from Entrepreneur: http://www. entrepreneur. com/article/70060# Kearns, K. (2010). Top 7 Tips for Motivating Your Team. Retrieved from Top 7 Business: http://top7business. com/? Top-7-Tips-for-Motivating-Your-Team&id=567 McCormick, M. (2012). Chron. Retrieved from How to Increase Employee Performance in the Workplace: http://smallbusiness. chron. com/increase-employee-performance-workplace-1950. html

The Death Of A Slaughter House - 1189 Words

â€Å"In the beginning God created the heavens and the earth†¦Ã¢â‚¬  (Genesis 1:1) He made animals for humans to eat, the truth is simple, yet humanity exacerbates it. Humans don’t cease to kill animals, void of mercy. And have managed to create the worst possible way to murder these priceless creatures. The death chamber that the humans use is called a slaughterhouse. A slaughter house is a large facility where humans keep the animals they will kill for meat. Below is the typical process of a slaughter house. â€Å"Slaughtering In slaughterhouses animals are received and kept around in stockyards and pens for 1 day. The animals are watered, but in most cases not fed unless they are kept more than 1 day. The animals are then driven from the holding†¦show more content†¦The cut is intended to kill, but on many occasions the workers cut off limbs of animals that are completely awake. Imagine being shot in the head by a stun gun, hung by your legs, your throat slit, and watching as your blood pours out of your body. Never thought of it like that, huh? That’s truth, it s about time someone said something that sends chills down your spine, because the truth should send chills up your spine. The truth should show you that it is wrong. The area of a slaughterhouse is very large, but to the animals inside, it is nothing but a bowl to a fish. How do humans live knowing that they are eating an animal that has been shown freedom, but never felt it? What is wrong with the world, more specifically, what is wrong with America? As a country America has worked off every part of its body to grant freedom to every people, as well as equality, and then they turn around and torture other beings. We are the land of the free, the land of the brave! Yet we cage animals as slaves, and cower from having anything to do with the matter. Many humans are very aware of the tragedies that take place in the slaughter houses, yet are persistent to supply the money to extend the torture of guiltless