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The Extracellular Matrix of diseased lung scaffolds and its role in 3D Bioprinting

Andersson, Isabel LU (2022) KBKM05 20221
Pure and Applied Biochemistry
Computational Chemistry
Abstract
Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death worldwide and for patients with end-stage disease, the only viable treatment is lung transplantation. In order to meet this clinical need, novel approaches of tissue engineering have emerged. 3D bioprinting technologies are one such rapidly evolving approach and show promising results in terms of biocompatibility, resolution and 3D distribution but still much research needs to be done in order to generate a bioengineered tissue that fully mimics the natural microenvironment and physiology of the human body. Using human extracellular matrix (ECM) as a starting material for 3D bioprinting could facilitate in accurately recapitulating these conditions.... (More)
Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death worldwide and for patients with end-stage disease, the only viable treatment is lung transplantation. In order to meet this clinical need, novel approaches of tissue engineering have emerged. 3D bioprinting technologies are one such rapidly evolving approach and show promising results in terms of biocompatibility, resolution and 3D distribution but still much research needs to be done in order to generate a bioengineered tissue that fully mimics the natural microenvironment and physiology of the human body. Using human extracellular matrix (ECM) as a starting material for 3D bioprinting could facilitate in accurately recapitulating these conditions. Previous work has shown that a lung-derived ECM/alginate hybrid material can be used as a biomaterial ink and retains its desirable properties during 3D bioprinting. Determining whether diseased scaffolds can be used as a starting material for bioinks is necessary for establishing a realistic, GxP compliant, up-scaled manufacturing process of the product. This thesis aims to further investigate the potential of this novel bioink formulation by comparison of generated bioinks derived from lung tissue of different patients and disease status. We found that all human lungs evaluated were decellularized and could be digested to form ECM solutions used to construct hybrid bioinks but differences across the sample cohort were found in proteomic composition. Furthermore, differences were observed in a chick chorioalloenteric membrane assay with regard to expression of angiogenic genes indicating that the source of ECM is an important consideration for generating clinical grade bioinks. (Less)
Popular Abstract (Swedish)
Lösningen till det globala underskottet tranplanterbara lungor finns kanske i återanvändandet av sjuk lungvävnad.

Över hela världens finns patienter som väntar på att få nya organ transplanterade. För de med kroniska lungsjukdomar finns ofta inga botemedel, och förhoppningen om att få nya lungor transplanterade präglas av långa väntelistor och bara ungefär hälften av de som faktiskt får transplantat överlever de första fem åren. För att bekämpa det här globala hälsoproblemet och hjälpa dessa patienter har nutidens forskning tagit till innovativa lösningar för att skapa konstgjord vävnad. Tänk om man i framtiden kan skapa artificiella lungor, som är anpassade och utformade efter patienten själv?
Vetenskapen om att skapa artificiell... (More)
Lösningen till det globala underskottet tranplanterbara lungor finns kanske i återanvändandet av sjuk lungvävnad.

Över hela världens finns patienter som väntar på att få nya organ transplanterade. För de med kroniska lungsjukdomar finns ofta inga botemedel, och förhoppningen om att få nya lungor transplanterade präglas av långa väntelistor och bara ungefär hälften av de som faktiskt får transplantat överlever de första fem åren. För att bekämpa det här globala hälsoproblemet och hjälpa dessa patienter har nutidens forskning tagit till innovativa lösningar för att skapa konstgjord vävnad. Tänk om man i framtiden kan skapa artificiella lungor, som är anpassade och utformade efter patienten själv?
Vetenskapen om att skapa artificiell lungvävnad genom teknik och ingenjörs skap har under de senaste 50 åren tagit fart. Extra uppmärksammat har tekniken 3D bioprintning blivit, i vilken man skapar en digital mall för vävnaden som ska skrivas ut och sedan använder celler och/eller biomaterial som bläck. Bläcket i fråga måste ha en rad specifika egenskaper för att kunna vara livskraftig i den slutgiltiga artificiella vävnaden. En av dessa viktiga egenskaper är att vävnaden måste kunna stödja tillväxten av kroppsegna blodkärl och få ett fungerande cirkulationssystem. Utan tillförsel av blod kommer den artificiella vävnaden inte få den syre och näringsämnen som behövs för att överleva.
Ytterligare en aspekt i skapandet av artificiell lungvävnad är biomaterialet i bläcket. Forskare tror att användandet av proteiner och strukturer (kallat extracellular matris (ECM)) som finns naturligt i kroppen kan bidra till att bläcket blir mer biologiskt aktivt, exempelvis att de stödjer tillväxten av nya blodkärl. Tekniken för att isolera dessa proteiner och strukturer kallas decellularisering och innebär att alla celler i lungan tas bort med kemikalier. Lungan blir då färglös och innehåller endast ECM.
Eftersom nästan alla friska mänskliga lungor som finns tillgängliga går direkt till transplantation, är de inte ett möjligt alternativ för råmaterial för 3D bioprintning. I denna avhandling diskuteras möjligheten att i stället använda lungor från patienter med Kronisk Obstruktiv Lungsjukdom (KOL), som finns i överflöd. Analyser görs för att avgöra om sjukdomen får konsekvenser för lungans ECM och möjligheter att formas till ett biobläck. Det diskuteras också hur ett sådant biobläck skulle kunna användas praktiskt i sjukvården, och vilka lagar och standarder som reglerar användningen. (Less)
Popular Abstract
The solution to the global shortage of transplantable lungs might lie in the reuse of diseased lung tissue.

All over the world there are patients waiting to have new organs transplanted. For those with chronic lung diseases, there is often no cure and the hope of receiving new lung transplants is tainted by long waiting lists and only about half of those who actually receive a transplant survive the first five years. To combat this global health problem and help these patients, today's research has turned to innovative solutions to create artificial tissue. What if in the future it is possible to create artificial lungs, which are adapted and designed according to the patient himself?
The science of creating artificial lung tissue... (More)
The solution to the global shortage of transplantable lungs might lie in the reuse of diseased lung tissue.

All over the world there are patients waiting to have new organs transplanted. For those with chronic lung diseases, there is often no cure and the hope of receiving new lung transplants is tainted by long waiting lists and only about half of those who actually receive a transplant survive the first five years. To combat this global health problem and help these patients, today's research has turned to innovative solutions to create artificial tissue. What if in the future it is possible to create artificial lungs, which are adapted and designed according to the patient himself?
The science of creating artificial lung tissue through technology and engineering has taken off over the past 50 years. The technology of 3D bioprinting has received extra attention, in which a digital template is created for the tissue to be printed and then cells and/or biomaterials are used as ink. The ink in question must have several specific properties to be viable in the final artificial tissue. One of these important properties is that the tissue must be able to support the growth of the body's own blood vessels and obtain a functioning circulatory system. Without the supply of blood, the artificial tissue will not receive the oxygen and nutrients it needs to survive.

Another aspect in the creation of artificial lung tissue is the biomaterial in the ink. Researchers believe that the use of proteins and structures (called extracellular matrix (ECM)) found naturally in the body can help make the ink more biologically active, for example by supporting the growth of new blood vessels. The technique to isolate these proteins and structures is called decellularization and means that all the cells in the lung are removed with chemicals, leaving the lung colorless and containing only ECM.

Since almost all healthy human lungs available go directly to transplantation, they are not a feasible option for raw materials for 3D bioprinting. In this thesis, the possibility of using lungs from patients with Chronic Obstructive Pulmonary Disease (COPD), which are abundant, is discussed instead. Analyzes are carried out to determine whether the disease has consequences for the lung's ECM and their ability to be formed into a bio-ink. It is also discussed how such a bio-ink could be used practically in healthcare, and which laws and standards regulate its use. (Less)
Please use this url to cite or link to this publication:
author
Andersson, Isabel LU
supervisor
organization
course
KBKM05 20221
year
type
H2 - Master's Degree (Two Years)
subject
keywords
Applied Biochemistry, hydrogel, extracellular matrix, ECM, chronic obstructive pulmonary disease, COPD
language
English
id
9098516
date added to LUP
2022-08-31 09:03:05
date last changed
2022-08-31 09:03:05
@misc{9098516,
  abstract     = {{Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death worldwide and for patients with end-stage disease, the only viable treatment is lung transplantation. In order to meet this clinical need, novel approaches of tissue engineering have emerged. 3D bioprinting technologies are one such rapidly evolving approach and show promising results in terms of biocompatibility, resolution and 3D distribution but still much research needs to be done in order to generate a bioengineered tissue that fully mimics the natural microenvironment and physiology of the human body. Using human extracellular matrix (ECM) as a starting material for 3D bioprinting could facilitate in accurately recapitulating these conditions. Previous work has shown that a lung-derived ECM/alginate hybrid material can be used as a biomaterial ink and retains its desirable properties during 3D bioprinting. Determining whether diseased scaffolds can be used as a starting material for bioinks is necessary for establishing a realistic, GxP compliant, up-scaled manufacturing process of the product. This thesis aims to further investigate the potential of this novel bioink formulation by comparison of generated bioinks derived from lung tissue of different patients and disease status. We found that all human lungs evaluated were decellularized and could be digested to form ECM solutions used to construct hybrid bioinks but differences across the sample cohort were found in proteomic composition. Furthermore, differences were observed in a chick chorioalloenteric membrane assay with regard to expression of angiogenic genes indicating that the source of ECM is an important consideration for generating clinical grade bioinks.}},
  author       = {{Andersson, Isabel}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{The Extracellular Matrix of diseased lung scaffolds and its role in 3D Bioprinting}},
  year         = {{2022}},
}