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

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. 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. Figure 1: Process of engineering tissues using decellularized ECM. (Gilpin & Yang 2017)

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. 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. 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

8. 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.

9. 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.

10. 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.

11. 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

12. QUESTION
AND
ANSWER

13. 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.

14. 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.