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CELL DERIVED
EXTRACELLULR MATRIX
(ECM)
IN TISSUE ENGINEERING
SCT60103
GENE TISSUE AND
CULTURE TECHNOLOGY
LAU SUET LING 032...
PRINCIPLE
A dynamic
microenvironment
which can directly or
indirectly regulate cell
adhesion, proliferation,
migration, an...
Figure 1: Process of engineering tissues using decellularized ECM. (Gilpin & Yang 2017)
WHAT IS DERMAL TISSUE ENGINEERING
Tissue Engineering is the practice of combining scaffolds, cells, and biologically activ...
THE PRINCIPAL OF CELL-DERIVED ECM IN
DERMAL TISSUE ENGINEERING
Tissue engineered skin substitute preparation involves cell...
CONTRIBUTIONS OF ECM TO DERMAL
TISSUE ENGINEERING
According to Strachan and Read (2004), ECM can be divided into several g...
CHARACTERISTICS OF CELL-DERIVED ECM THAT
PROMOTES SKIN REGENERATION
(1) Biodegradability:
• For the formation of functiona...
CHARACTERISTICS OF CELL-DERIVED ECM THAT
PROMOTES SKIN REGENERATION
(4) Porosity:
• Permit cellular permeability, diffusiv...
THE CURRENT DEVELOPMENT OF CELL-DERIVED
ECM FOR DERMAL TISSUE ENGINEERING
• Fibroblasts to make cell-derived dermal substi...
THE ADVANTAGES AND DISADVANTAGES OF
CELL-DERIVED ECM IN DERMAL TISSUE ENGINEERING
ADVANTAGES:
 Accessible from human cell...
QUESTION
AND
ANSWER
REFERENCES
Ahlfors, J., & Billiar, K. (2007), ‘Biomechanical and biochemical characteristics of a human fibroblast-produce...
REFERENCES
Hellewell, AL, Rosini, S & Adams, JC 2017, ‘A Rapid, Scalable Method for the Isolation, Functional Study, and A...
CELL-DERIVED EXTRACELLUALR MATRIX (ECM) IN TISSUE ENGINEERING [SCT60103 GENE AND TISSUE CULTURE TECHNOLOGY]
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CELL-DERIVED EXTRACELLUALR MATRIX (ECM) IN TISSUE ENGINEERING [SCT60103 GENE AND TISSUE CULTURE TECHNOLOGY]

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The application of cell-derived extracellular matrix (ECM) in dermal tissue engineering.

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CELL-DERIVED EXTRACELLUALR MATRIX (ECM) IN TISSUE ENGINEERING [SCT60103 GENE AND TISSUE CULTURE TECHNOLOGY]

  1. 1. CELL DERIVED EXTRACELLULR MATRIX (ECM) IN TISSUE ENGINEERING SCT60103 GENE TISSUE AND CULTURE TECHNOLOGY LAU SUET LING 0324823 PREVEENA RAVI 0325157 DEEROSHAA THEVENDERAN 0324114 ESWEREA ANPARASAN 0324943 CHALANI GANESON 0329282
  2. 2. PRINCIPLE A dynamic microenvironment which can directly or indirectly regulate cell adhesion, proliferation, migration, and differentiation. WHAT IS A CELL-DERIVED ECM? • Obtained from mesenchymal stem cells, chondrocytes, fibroblasts etc. • Cell-derived ECM scaffolds contain fibrillar proteins, matrix macromolecules and associated growth factors that closely resemble native ECM microenvironments. • Three main considerations: Cell source, culture method and processing method. • Both primary cells and cell lines have been used to produce cell- derived ECM (Hellewell, Rosini & Adams 2017). • Obtained through the process of decellularization (Elmashhady et al. 2017).
  3. 3. Figure 1: Process of engineering tissues using decellularized ECM. (Gilpin & Yang 2017)
  4. 4. WHAT IS DERMAL TISSUE ENGINEERING Tissue Engineering is the practice of combining scaffolds, cells, and biologically active molecules to produce functional tissues. There are 2 approaches in tissue engineering (Howard et al., 2008): 1. Scaffolding. 2. Using the scaffold as a growth factor/drug delivery device. Dermal tissue enginering: The incorporation of scaffold matrices to fill in the tissue voild in cases of deep injuries and burns. In cases of deep injuries and burns, the process of healing is inadequate which leads to a chronic wound. Thus, any loss of full-thickness skin more than 4 cm diameter needs grafting for its treatment. Types of dermal tissue engineering (Vig et al., 2017) : 1. Skin Grafting with autograpft 2. Epithelial Cell Seeding 3. Cell cocultures
  5. 5. THE PRINCIPAL OF CELL-DERIVED ECM IN DERMAL TISSUE ENGINEERING Tissue engineered skin substitute preparation involves cells and extracellular matrix (ECM) ECM scaffolds derived from mesenchymal stem cell (MSC), chondrocyte, and fibroblast were prepared by culturing cells in a selectively removable poly(lactic-co-glycolic acid) (PLGA) template, a biodegradable polymer-based tissue scaffolds (Lu et al., 2011). ECMs are secreted molecules that constitute the cell microenvironment and are composed of a dynamic and complex array of glycoproteins, collagens, glycosaminoglycans (GAGs), and proteoglycans (PGs).  In tissues such as the skin, the repair of the dermis after wounding requires : The fibroblasts that produce the ECM molecules, the overlying epithelial layer (keratinocytes), white blood cells such as neutrophils and macrophages, which together orchestrate the cytokine-mediated signaling which regulates the proper extent and timing of the repair process (Ghatak et al., 2015).
  6. 6. CONTRIBUTIONS OF ECM TO DERMAL TISSUE ENGINEERING According to Strachan and Read (2004), ECM can be divided into several groups:  Structural proteins:  Collagens  Elastins  Adhesion proteins:  Laminins  Fibronectins  Proteoglycans:  Comprise of a core protein associated with various glycosaminoglycans.  Free GAG:  Hyaluronic acid
  7. 7. CHARACTERISTICS OF CELL-DERIVED ECM THAT PROMOTES SKIN REGENERATION (1) Biodegradability: • For the formation of functional microvascular networks and remodelling: in practice, the role of the scaffold is temporary, and is required only until the patient’s own ECM can replace the implanted structures. (2) Structural support: • Cells must be able to adhere onto a solid surface, grow , migrate, and proliferate until they can function normally similar to the surrounding tissues. (3) Mechanical property: • Scaffolds have to provide sufficient mechanical properties similar to the native matrix at the implanted sites. • Mechanical properties such as elasticity, toughness an rigidity will differ depending on the anatomical sites for required functions. • Insufficient properties may cause damage to the scaffold upon handling.
  8. 8. CHARACTERISTICS OF CELL-DERIVED ECM THAT PROMOTES SKIN REGENERATION (4) Porosity: • Permit cellular permeability, diffusivity of molecular substrates and nutrients and vascularization throug out the scaffold. • The engineered tissue can be nourished by the vascularized matrices to ensure the efficiency of better transplantation. (6) Manufacturing capacity and technology: • Cost effective (5) Biocompatibility and bioactivities: • Non- biocompatibility can evoke chronic i nflammatory response or severe immun e response which will cause rejection of th e scaffold • Scaffolds should provide bioactive cues and growth factors to regulate the cellular activities.
  9. 9. THE CURRENT DEVELOPMENT OF CELL-DERIVED ECM FOR DERMAL TISSUE ENGINEERING • Fibroblasts to make cell-derived dermal substitutes and acellular scaffolds to treat skin loss and repair • Have garnered much attention as mediators of scar formation as they enable increased hydration of the epidermis covering the scar and minimize the risk of infection in the healing wound. • Serving as physical support to promote tissue organization, resist aggressive wound contraction and scar tissue formation.
  10. 10. THE ADVANTAGES AND DISADVANTAGES OF CELL-DERIVED ECM IN DERMAL TISSUE ENGINEERING ADVANTAGES:  Accessible from human cells  Able to use various somatic and stem cells to generate optimal matrices with desirable properties  The three-dimensional architecture of the scaffold enhances the activity of the cells seeded on to it.  Provide the option of using the patient’s own autologous cells, which can be expanded in the laboratory for scaffold fabrication.  The procedure for isolating patient cells is much less invasive than taking an autologous graft, and can be beneficial for patients with limited undamaged donor sites. DISADVANTAGES:  Fabricating the scaffolds from cells takes more time than decellularizing tissue.  The decellularization and processing methods can affect the structure and mechanical strength of the scaffold
  11. 11. QUESTION AND ANSWER
  12. 12. REFERENCES Ahlfors, J., & Billiar, K. (2007), ‘Biomechanical and biochemical characteristics of a human fibroblast-produced and remodeled matrix’, Bio materials, vol.28, pp. 2183-2191. Elmashhady, HH, Kraemer, BA, Patel, KH, Sell, SA & Garg, K 2017, ‘Decellularized extracellular matrices for tissue engineering applications ’, Electrospinning, vol. 1, no. 1, viewed 9 April 2018, https://www.degruyter.com/downloadpdf/j/esp.2017.1.issue-1/esp-2017-0005/esp-2017- 0005.pdf. El Ghalbzouri, A, Commandeur, S, Rietveld, MH, Mulder, AA & Willemze, R 2009, ‘Replacement of animal-derived collagen matrix by huma n fibroblast-derived dermal matrix for human skin equivalent products’, Biomaterials, vol.30, pp. 71-8]. Fitzpatrick, L.E. & McDevitt, T.C., 2015, Cell-derived matrices for tissue engineering and regenerative medicine applications, Biomater Sci, v ol. 3(1), pp.12-24. Strachan, T & Read, A.P., (2004), Human Molecular Genetics 3. 3rd edn, Garland Science, New York. Fitzpatrick,L.E & McDevitt,T.C. (2005),‘Cell-derived matrices for tissue engineering and regenerative medicine applications’, Biomater Sci., vol.3,pp.12-24 Fioleda, P., Jennifer, C. & Sarah, M 2012, ‘Design and Fabrication of a Novel Cell-Derived Matrix Scaffold for Dermal Wound Healing’, Degr ee thesis, Worcester Polytechnic Institute, Massachusetts. Ghatak, S., Maytin, E., Mack, J., Hascall, V., Atanelishvili, I., Moreno Rodriguez, R., Markwald, R. and Misra, S. (2015). Roles of Proteoglyc ans and Glycosaminoglycans in Wound Healing and Fibrosis. [online] Hindawi.com. Available at: https://www.hindawi.com/journals/ijcb/201 5/834893/ [Accessed 14 Apr. 2018]. Gilpin, A & Yang, Y 2017, Process of engineering tissues using decellularized ECM, BioMed Research International, USA.
  13. 13. REFERENCES Hellewell, AL, Rosini, S & Adams, JC 2017, ‘A Rapid, Scalable Method for the Isolation, Functional Study, and Analysis of Cell-derived Extr acellular Matrix’, Journal of Visualized Experiments: JoVE, vol. 119, viewed 9 April 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC53 51878/#. Hongxu, L,Takashi, H, Naoki,K,Ichie,K,Minghui,S & Guoping,C. (2011), ‘Cultured cell-derived extracellular matrix scaffolds for tissue engin eering’, Biomaterials, vol.32, pp. 9658-9666. Howard, D., Buttery, L., Shakesheff, K. and Roberts, S. (2008). Tissue engineering: strategies, stem cells and scaffolds. [online] NCBI. Availa ble at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475566/ [Accessed 14 Apr. 2018]. Hyojin, K., Ik, K.K., Kwanwoo, S. & Youhwan, K. 2016, ‘Extracellular Matrix Revisited: Roles in Tissue Engineering’, International Neurolo gy Journal, vol. 20, no. 2, viewed 9 April 201, <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895908/> Lu, H., Hoshiba, T., Kawazoe, N., Koda, I., Song, M. and Chen, G. (2011). Cultured cell-derived extracellular matrix scaffolds for tissue engin eering. - PubMed - NCBI. [online] Ncbi.nlm.nih.gov. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21937104 [Accessed 14 Apr. 2018]. Vig, K., Chaudhari, A., Tripathi, S., Dixit, S., Sahu, R., Pillai, S., Dennis, V. and Singh, S. (2017). Advances in Skin Regeneration Using Tissu e Engineering. [online] NCBI. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412373/ [Accessed 14 Apr. 2018]. Xue, M. & Jackson, C.J., 2015, Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring, Advances i n Wound Care, vol. 1 (3), pp.119-136.

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