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Characterization of Decellularized Implants for Extracellular Matrix Integrity and Immune Response Elicitation

Banerjee, Debashish ; Nayakawde, Nikhil B. ; Antony, Deepti ; Deshmukh, Meghshree ; Ghosh, Sudip LU ; Sihlbom, Carina ; Berger, Evelin ; Ul Haq, Uzair and Olausson, Michael (2022) In Tissue Engineering - Part A 28(13-14). p.621-639
Abstract

Biological scaffold is a popular choice for the preparation of tissue-engineered organs and has the potential to address donor shortages in clinics. However, biological scaffolds prepared by physical or chemical agents cause damage to the extracellular matrix (ECM) by potentially inducing immune responses after implantation. The current study explores the fate of the decellularized (DC) scaffolds using a cocktail of chemicals following implantation without using immunosuppressants. Using the syngeneic (Lewis male-Lewis female) and allogeneic (Brown Norway male-Lewis female) models and different tissue routes (subcutaneous vs. omentum) for implantation, we applied in-depth quantitative proteomics, genomics along with histology and... (More)

Biological scaffold is a popular choice for the preparation of tissue-engineered organs and has the potential to address donor shortages in clinics. However, biological scaffolds prepared by physical or chemical agents cause damage to the extracellular matrix (ECM) by potentially inducing immune responses after implantation. The current study explores the fate of the decellularized (DC) scaffolds using a cocktail of chemicals following implantation without using immunosuppressants. Using the syngeneic (Lewis male-Lewis female) and allogeneic (Brown Norway male-Lewis female) models and different tissue routes (subcutaneous vs. omentum) for implantation, we applied in-depth quantitative proteomics, genomics along with histology and quantitative image analysis tools to comprehensively describe and compare the proteins following DC and postimplantation. Our data helped to identify any alteration postdecullarization as well implantation. We could also monitor route-specific modulation of the ECM and regulation of the immune responses (macrophage and T cells) following implantation. The current approach opens up the possibility to monitor the fate of biological scaffolds in terms of the ECM and immune response against the implants. In addition, the identification of different routes helped us to identify differential immune responses against the implants. This study opens up the potential to identify the changes associated with chemical DC both pre- and postimplantation, which could further help to promote research in this direction. The development of a biological scaffold helps in the preparation of a functional organ in the clinics. In the current study, we develop a strategy for chemical decellularization and explored two different routes to understand the differential responses elicited postimplantation. The use of sensitive protein and genomic tools to study the changes creates a favorable environment for similar efforts to develop and characterize biological scaffolds before further trials in the clinics. The current study, which was carried out without any immunosuppressive agents, could help to establish (a) appropriate chemical strategies for preparing biological scaffolds as well as (b) identify putative implantable routes to circumvent any adverse immune reactions, which will ultimately decide the outcome for acceptance or rejection of the scaffold/implant.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
decellularization, extracellular matrix, immune response, implants, syn/allogeneic, vascular scaffold
in
Tissue Engineering - Part A
volume
28
issue
13-14
pages
19 pages
publisher
Mary Ann Liebert, Inc.
external identifiers
  • scopus:85134387273
  • pmid:34963315
ISSN
1937-3341
DOI
10.1089/ten.tea.2021.0146
language
English
LU publication?
yes
id
d04e6f68-ce03-41eb-a8fc-4b8f3690a41e
date added to LUP
2022-09-26 15:01:17
date last changed
2024-06-13 14:55:46
@article{d04e6f68-ce03-41eb-a8fc-4b8f3690a41e,
  abstract     = {{<p>Biological scaffold is a popular choice for the preparation of tissue-engineered organs and has the potential to address donor shortages in clinics. However, biological scaffolds prepared by physical or chemical agents cause damage to the extracellular matrix (ECM) by potentially inducing immune responses after implantation. The current study explores the fate of the decellularized (DC) scaffolds using a cocktail of chemicals following implantation without using immunosuppressants. Using the syngeneic (Lewis male-Lewis female) and allogeneic (Brown Norway male-Lewis female) models and different tissue routes (subcutaneous vs. omentum) for implantation, we applied in-depth quantitative proteomics, genomics along with histology and quantitative image analysis tools to comprehensively describe and compare the proteins following DC and postimplantation. Our data helped to identify any alteration postdecullarization as well implantation. We could also monitor route-specific modulation of the ECM and regulation of the immune responses (macrophage and T cells) following implantation. The current approach opens up the possibility to monitor the fate of biological scaffolds in terms of the ECM and immune response against the implants. In addition, the identification of different routes helped us to identify differential immune responses against the implants. This study opens up the potential to identify the changes associated with chemical DC both pre- and postimplantation, which could further help to promote research in this direction. The development of a biological scaffold helps in the preparation of a functional organ in the clinics. In the current study, we develop a strategy for chemical decellularization and explored two different routes to understand the differential responses elicited postimplantation. The use of sensitive protein and genomic tools to study the changes creates a favorable environment for similar efforts to develop and characterize biological scaffolds before further trials in the clinics. The current study, which was carried out without any immunosuppressive agents, could help to establish (a) appropriate chemical strategies for preparing biological scaffolds as well as (b) identify putative implantable routes to circumvent any adverse immune reactions, which will ultimately decide the outcome for acceptance or rejection of the scaffold/implant.</p>}},
  author       = {{Banerjee, Debashish and Nayakawde, Nikhil B. and Antony, Deepti and Deshmukh, Meghshree and Ghosh, Sudip and Sihlbom, Carina and Berger, Evelin and Ul Haq, Uzair and Olausson, Michael}},
  issn         = {{1937-3341}},
  keywords     = {{decellularization; extracellular matrix; immune response; implants; syn/allogeneic; vascular scaffold}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{13-14}},
  pages        = {{621--639}},
  publisher    = {{Mary Ann Liebert, Inc.}},
  series       = {{Tissue Engineering - Part A}},
  title        = {{Characterization of Decellularized Implants for Extracellular Matrix Integrity and Immune Response Elicitation}},
  url          = {{http://dx.doi.org/10.1089/ten.tea.2021.0146}},
  doi          = {{10.1089/ten.tea.2021.0146}},
  volume       = {{28}},
  year         = {{2022}},
}