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Article: Angiogenesis and Re-endothelialization in decellularized scaffolds: Recent advances and current challenges in tissue engineering.

Mazloomnejad, Radman / Babajani, Amirhesam / Kasravi, Mohammadreza / Ahmadi, Armin / Shariatzadeh, Siavash / Bahrami, Soheyl / Niknejad, Hassan

Frontiers in bioengineering and biotechnology

2023 Volume 11, Page(s) 1103727

Abstract: Decellularization of tissues and organs has recently become a promising approach in tissue engineering and regenerative medicine to circumvent the challenges of organ donation and complications of transplantations. However, one main obstacle to reaching ... ...

Abstract	Decellularization of tissues and organs has recently become a promising approach in tissue engineering and regenerative medicine to circumvent the challenges of organ donation and complications of transplantations. However, one main obstacle to reaching this goal is acellular vasculature angiogenesis and endothelialization. Achieving an intact and functional vascular structure as a vital pathway for supplying oxygen and nutrients remains the decisive challenge in the decellularization/re-endothelialization procedure. In order to better understand and overcome this issue, complete and appropriate knowledge of endothelialization and its determining variables is required. Decellularization methods and their effectiveness, biological and mechanical characteristics of acellular scaffolds, artificial and biological bioreactors, and their possible applications, extracellular matrix surface modification, and different types of utilized cells are factors affecting endothelialization consequences. This review focuses on the characteristics of endothelialization and how to optimize them, as well as discussing recent developments in the process of re-endothelialization.
Language	English
Publishing date	2023-02-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2023.1103727
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Article ; Online: Targeted Association and Intracellular Delivery of Nanocargoes into Primary T Lymphocytes via Interleukin-2 Receptor-Mediated Endocytosis.

Ayyadevara, V S S Abhinav / Ahmadi, Armin / Roh, Kyung-Ho

Bioconjugate chemistry

2021 Volume 32, Issue 8, Page(s) 1675–1687

Abstract: Despite the tremendous progress in immunotherapy regimens using T cells, efforts to modulate the functions of T cells are still significantly hampered by the lack of reliable methods to deliver various cargoes into the T cells. This ongoing challenge ... ...

Abstract	Despite the tremendous progress in immunotherapy regimens using T cells, efforts to modulate the functions of T cells are still significantly hampered by the lack of reliable methods to deliver various cargoes into the T cells. This ongoing challenge originates from the intrinsic resistance of T cells in taking up exogenous materials. Here, we strategically aimed to hijack the natural endocytosis of Interleukin-2 (IL2) by the activated T cells for the targeted association and intracellular delivery of cargoes in varying sizes. First, we carefully characterized the fluctuations in the expression levels of IL2 receptor (IL2R) subunits (CD25, CD122, and CD132) during the murine primary T cell cultures over 12 days. We identified the highest fraction of T cells that would express the high-affinity trimeric IL2R on Day 3. By examining the association and uptake efficiencies of IL2 molecules that are biotinylated via either random lysine-targeting chemical reaction (using NHS-PEG4-Biotin) or site-specific enzymatic modification (using Avitag sequence), we demonstrated that the most efficient delivery of cargo can be achieved by C-terminal conjugation. Upon confirmation of successful delivery of a small model cargo, streptavidin, we employed superparamagnetic iron oxide nanoparticles (SPIONs) as bigger model cargoes having core diameters of 50, 100, and 200 nm. We examined the association and intracellular delivery of the IL2-conjugated nanocargoes using flow cytometry, confocal laser scanning microscopy, and transmission electron microscopy. While cargoes of all tested sizes were successfully associated with the IL2R-expressing T cells in comparable efficiencies, the uptake efficiencies were inversely proportional to the sizes of the cargoes. Nevertheless, our current definitive report confirms that nanocargoes with a practical maximum size limit around 100-200 nm can be intracellularly delivered into activated primary T cells using IL2R-mediated endocytosis, which opens a new horizon for engineering and manufacturing of various T cell immunotherapeutics.
MeSH term(s)	Animals ; Endocytosis ; Gene Expression Regulation ; Humans ; Interleukin-2/chemistry ; Magnetic Iron Oxide Nanoparticles/chemistry ; Mice ; Mice, Inbred C57BL ; Nanotechnology ; Protein Subunits ; Receptors, Interleukin-2/metabolism ; Spleen/cytology ; T-Lymphocytes/metabolism
Chemical Substances	IL2 protein, human ; Interleukin-2 ; Protein Subunits ; Receptors, Interleukin-2
Language	English
Publishing date	2021-07-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.1c00212
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Article ; Online: Evaluation of immunomodulatory effects of co-culture or supernatant of dexamethasone or IFN-γ-treated adipose-derived mesenchymal stem cells on spleen mononuclear cells

Bayati, Fatemeh / Valadi, Maryam / Ahmadi, Armin / Najafi, Farangis / Ansaripour, Bita / Sharif-Paghaleh, Ehsan

European cytokine network

2023 Volume 33, Issue 3, Page(s) 70–78

Abstract: Although mesenchymal stem cells (MSCs) have exhibited promising immunomodulatory potential in preclinical studies, clinical studies have revealed variable results. These results often depend on environmental cues. Pre-conditioning MSCs with cytokines is ... ...

Abstract	Although mesenchymal stem cells (MSCs) have exhibited promising immunomodulatory potential in preclinical studies, clinical studies have revealed variable results. These results often depend on environmental cues. Pre-conditioning MSCs with cytokines is one of the methods used to enhance their immunomodulatory effects. In this study, we harvested adipose-derived MSCs from mice and cultured them with different doses of the cytokine, IFN-γ, and the corticosteroid drug, dexamethasone, in order to investigate their effects on MSC immunosuppressive function. We found the co-culture or supernatant of MSCs, pre-conditioned with IFN-γ, together with spleen mononuclear cells resulted in a significant reduction of mononuclear cell proliferation. Although the supernatant of MSCs, pre-conditioned with dexamethasone, showed similar results, dexamethasone pre-conditioning of co-cultured MSCs increased mononuclear cell proliferation. The results further our understanding of immune-related effects of MSCs which may provide a basis for further in vivo studies to achieve better clinical results. We propose that pre-conditioning with cytokines might be an effective method to boost the immunomodulatory effects of MSCs.
MeSH term(s)	Mice ; Animals ; Coculture Techniques ; Spleen ; Interferon-gamma ; Cytokines ; Dexamethasone/pharmacology ; Mesenchymal Stem Cells
Chemical Substances	Interferon-gamma (82115-62-6) ; Cytokines ; Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	2023-04-13
Publishing country	France
Document type	Journal Article
ZDB-ID	1118857-1
ISSN	1952-4005 ; 1148-5493
ISSN (online)	1952-4005
ISSN	1148-5493
DOI	10.1684/ecn.2022.0482
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Article ; Online: Calcium signaling on Jurkat T cells induced by microbeads coated with novel peptide ligands specific to human CD3ε.

Ahmadi, Armin / Ayyadevara, V S S Abhinav / Baudry, Jerome / Roh, Kyung-Ho

Journal of materials chemistry. B

2021 Volume 9, Issue 6, Page(s) 1661–1675

Abstract: CD3ε is expressed on T lymphocytes as a part of the T cell receptor (TCR)-CD3 complex. Together with other CD3 molecules, CD3ε is responsible for the activation of T cells via transducing the event of antigen recognition by the TCR into intracellular ... ...

Abstract	CD3ε is expressed on T lymphocytes as a part of the T cell receptor (TCR)-CD3 complex. Together with other CD3 molecules, CD3ε is responsible for the activation of T cells via transducing the event of antigen recognition by the TCR into intracellular signaling cascades. The present study first aims to identify a novel peptide ligand that binds to human CD3ε in a specific manner and to perform an initial evaluation of its biological efficacy on the human T cell line, Jurkat cells. We screened a phage-display peptide library against human CD3ε using a subtractive biopanning process, from which we identified 13 phage clones displaying unique peptide sequences. One dominant phage clone displaying the 7 amino acid sequence of WSLGYTG, which occupied 90% of tested plaques (18 out of 20) after the 5th round of biopanning, demonstrated a superior binding behavior to other clones in the binding assays against recombinant CD3ε on microbeads or Jurkat cells. The synthesized peptide also showed specific binding to Jurkat cells in a dose-dependent manner but not to B cell lymphoma line, 2PK3 cells. Molecular modeling and docking simulation confirmed that the selected peptide ligand in an energetically stable conformation binds to a pocket of CD3ε that is not hidden by either CD3γ or CD3δ. Lastly, magnetic microbeads conjugated with the synthesized peptide ligands showed a weak but specific association with Jurkat cells and induced the calcium flux, a hallmark indication of proximal T cell receptor signaling, which gave rise to an enhancement of IL-2 section and cell proliferation. The novel peptide ligand and its various multivalent forms have a great potential in applications related to T cell biology and T cell immunotherapy.
MeSH term(s)	Animals ; CD3 Complex/chemistry ; CD3 Complex/metabolism ; Calcium Signaling/drug effects ; Cells, Cultured ; Coated Materials, Biocompatible/chemistry ; Coated Materials, Biocompatible/pharmacology ; Humans ; Jurkat Cells ; Ligands ; Mice ; Particle Size ; Peptides/chemistry ; Peptides/pharmacology ; Surface Properties
Chemical Substances	CD3 Complex ; CD3 antigen, gamma chain ; Coated Materials, Biocompatible ; Ligands ; Peptides
Language	English
Publishing date	2021-01-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2702241-9
ISSN	2050-7518 ; 2050-750X
ISSN (online)	2050-7518
ISSN	2050-750X
DOI	10.1039/d0tb02235g
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Article ; Online: Osteogenic Differentiation Effect of BMP-9 with Phenamil and Simvastatin on Intact Human Amniotic Epithelial Stem Cells

Ahmadi, Armin / Ebadi, Seyed Shayan / Tayebi, Tahereh / Ebadi, Seyed Alireza / Sarzaeem, Mohammad Mahdi / Niknejad, Hassan

Iranian biomedical journal

2022 Volume 26, Issue 6, Page(s) 463–474

Abstract: Background: Background: Bone tissue engineering has shown to be a promising strategy for repairing bone defects without causing harmful side effects to the patient. Three main building blocks of tissue engineering, including seeding cells, scaffold, and ...

Abstract	Background: Background: Bone tissue engineering has shown to be a promising strategy for repairing bone defects without causing harmful side effects to the patient. Three main building blocks of tissue engineering, including seeding cells, scaffold, and signaling molecules, are required for adequate bone regeneration. The human amniotic membrane (hAM) is the innermost of the placental membranes. In addition to providing a source of stem cells and growth factors, hAM has several features that make it an appropriate scaffold containing stem cells for use in tissue engineering purposes. The present investigation aimed to assess the effect of bone morphogenetic protein-9 (BMP-9) combined with phenamil and simvastatin on osteogenic induction of hAM with its human amniotic membrane epithelial cells (hAECs). Method: Methods: Using six different osteogenic medium (OMs), we cultured hAM for 14 days. The basic OMs were chosen as the first group and other media were made by adding BMP-9, phenamil, simvastatin, BMP-9 alongside phenamil, and BMP-9 alongside simvastatin to the basic OMs. Finally, viability assay, tissue mineralization, calcium and phosphate content determination, and measurement of lactic acid dehydrogenase (LDH), and alkaline phosphatase (ALP) activity were performed. Results: Results: Among all study groups, groups containing simvastatin showed a significantly lower level of viability. Although all media could induce osteogenic features, the hAECs cultured in media containing BMP-9 and phenamil demonstrated a wider area of mineralization and a significantly higher level of calcium and phosphate content, LDH, and ALP activity. Conclusion: Conclusion: Our findings indicated that the use of phenamil together with BMP-9 could synergistically show in situ osteogenic induction in hAECs, which could be a new insight into translational medicine.
MeSH term(s)	Female ; Pregnancy ; Humans ; Osteogenesis ; Growth Differentiation Factor 2/pharmacology ; Simvastatin/pharmacology ; Placenta ; Cell Differentiation ; Stem Cells ; Cells, Cultured
Chemical Substances	Growth Differentiation Factor 2 ; Simvastatin (AGG2FN16EV) ; phenylamil (2038-35-9)
Language	English
Publishing date	2022-11-01
Publishing country	Iran
Document type	Journal Article
ZDB-ID	2489282-8
ISSN	2008-823X ; 1028-852X
ISSN (online)	2008-823X
ISSN	1028-852X
DOI	10.52547/ibj.3748
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Article: Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine.

Kasravi, Mohammadreza / Ahmadi, Armin / Babajani, Amirhesam / Mazloomnejad, Radman / Hatamnejad, Mohammad Reza / Shariatzadeh, Siavash / Bahrami, Soheyl / Niknejad, Hassan

Biomaterials research

2023 Volume 27, Issue 1, Page(s) 10

Abstract: Tissue-engineered decellularized extracellular matrix (ECM) scaffolds hold great potential to address the donor shortage as well as immunologic rejection attributed to cells in conventional tissue/organ transplantation. Decellularization, as the key ... ...

Abstract	Tissue-engineered decellularized extracellular matrix (ECM) scaffolds hold great potential to address the donor shortage as well as immunologic rejection attributed to cells in conventional tissue/organ transplantation. Decellularization, as the key process in manufacturing ECM scaffolds, removes immunogen cell materials and significantly alleviates the immunogenicity and biocompatibility of derived scaffolds. However, the application of these bioscaffolds still confronts major immunologic challenges. This review discusses the interplay between damage-associated molecular patterns (DAMPs) and antigens as the main inducers of innate and adaptive immunity to aid in manufacturing biocompatible grafts with desirable immunogenicity. It also appraises the impact of various decellularization methodologies (i.e., apoptosis-assisted techniques) on provoking immune responses that participate in rejecting allogenic and xenogeneic decellularized scaffolds. In addition, the key research findings regarding the contribution of ECM alterations, cytotoxicity issues, graft sourcing, and implantation site to the immunogenicity of decellularized tissues/organs are comprehensively considered. Finally, it discusses practical solutions to overcome immunogenicity, including antigen masking by crosslinking, sterilization optimization, and antigen removal techniques such as selective antigen removal and sequential antigen solubilization.
Language	English
Publishing date	2023-02-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2775188-0
ISSN	2055-7124 ; 1226-4601
ISSN (online)	2055-7124
ISSN	1226-4601
DOI	10.1186/s40824-023-00348-z
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Article ; Online: Exosomal Cargo: Pro-angiogeneic, anti-inflammatory, and regenerative effects in ischemic and non-ischemic heart diseases - A comprehensive review.

Amirzadeh Gougheri, Kowsar / Ahmadi, Armin / Ahmadabadi, Mohadeseh Ghafuri / Babajani, Amirhesam / Yazdanpanah, Ghasem / Bahrami, Soheyl / Hassani, Mohammad / Niknejad, Hassan

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 168, Page(s) 115801

Abstract: Heart diseases are the primary cause of mortality and morbidity worldwide which inflict a heavy social and economic burden. Among heart diseases, most deaths are due to myocardial infarction (MI) or heart attack, which occurs when a decrement in blood ... ...

Abstract	Heart diseases are the primary cause of mortality and morbidity worldwide which inflict a heavy social and economic burden. Among heart diseases, most deaths are due to myocardial infarction (MI) or heart attack, which occurs when a decrement in blood flow to the heart causes injury to cardiac tissue. Despite several available diagnostic, therapeutic, and prognostic approaches, heart disease remains a significant concern. Exosomes are a kind of small extracellular vesicles released by different types of cells that play a part in intercellular communication by transferring bioactive molecules important in regenerative medicine. Many studies have reported the diagnostic, therapeutic, and prognostic role of exosomes in various heart diseases. Herein, we reviewed the roles of exosomes as new emerging agents in various types of heart diseases, including ischemic heart disease, cardiomyopathy, arrhythmia, and valvular disease, focusing on pathogenesis, therapeutic, diagnostic, and prognostic roles in different areas. We have also mentioned different routes of exosome delivery to target tissues, the effects of preconditioning and modification on exosome's capability, exosome production in compliance with good manufacturing practice (GMP), and their ongoing clinical applications in various medical contexts to shed light on possible clinical translation.
MeSH term(s)	Humans ; Myocardial Ischemia/therapy ; Myocardial Infarction/pathology ; Cell Communication/physiology ; Regenerative Medicine ; Anti-Inflammatory Agents
Chemical Substances	Anti-Inflammatory Agents
Language	English
Publishing date	2023-10-31
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.115801
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Article ; Online: Wet-spinnability and crosslinked Fiber properties of alginate/hydroxyethyl cellulose with varied proportion for potential use in tendon tissue engineering.

Hojabri, Mahsa / Tayebi, Tahereh / Kasravi, Mohammadreza / Aghdaee, Amirhossein / Ahmadi, Armin / Mazloomnejad, Radman / Tarasi, Roghayeh / Shaabani, Alireza / Bahrami, Soheyl / Niknejad, Hassan

International journal of biological macromolecules

2023 Volume 240, Page(s) 124492

Abstract: Researchers have examined different bio-inspired materials in tissue engineering and regenerative medicine to fabricate scaffolds to address tendon regeneration requirements. We developed fibers based on alginate (Alg) and hydroxyethyl cellulose (HEC) by ...

Abstract	Researchers have examined different bio-inspired materials in tissue engineering and regenerative medicine to fabricate scaffolds to address tendon regeneration requirements. We developed fibers based on alginate (Alg) and hydroxyethyl cellulose (HEC) by wet-spinning technique to mimic the fibrous sheath of ECM. Various proportions (25:75, 50:50, 75:25) of 1 % Alg and 4 % HEC were blended to this aim. Two steps of crosslinking with different concentrations of CaCl
MeSH term(s)	Animals ; Tissue Engineering/methods ; Alginates ; Cellulose ; Regenerative Medicine ; Tendons ; Tissue Scaffolds
Chemical Substances	Alginates ; Cellulose (9004-34-6)
Language	English
Publishing date	2023-04-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2023.124492
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Article: Calcium signaling on Jurkat T cells induced by microbeads coated with novel peptide ligands specific to human CD3ε

Ahmadi, Armin / Ayyadevara, V. S. S. Abhinav / Baudry, Jerome / Roh, Kyung-Ho

Journal of materials chemistry B. 2021 Feb. 19, v. 9, no. 6

2021

Abstract	CD3ε is expressed on T lymphocytes as a part of the T cell receptor (TCR)-CD3 complex. Together with other CD3 molecules, CD3ε is responsible for the activation of T cells via transducing the event of antigen recognition by the TCR into intracellular signaling cascades. The present study first aims to identify a novel peptide ligand that binds to human CD3ε in a specific manner and to perform an initial evaluation of its biological efficacy on the human T cell line, Jurkat cells. We screened a phage-display peptide library against human CD3ε using a subtractive biopanning process, from which we identified 13 phage clones displaying unique peptide sequences. One dominant phage clone displaying the 7 amino acid sequence of WSLGYTG, which occupied 90% of tested plaques (18 out of 20) after the 5th round of biopanning, demonstrated a superior binding behavior to other clones in the binding assays against recombinant CD3ε on microbeads or Jurkat cells. The synthesized peptide also showed specific binding to Jurkat cells in a dose-dependent manner but not to B cell lymphoma line, 2PK3 cells. Molecular modeling and docking simulation confirmed that the selected peptide ligand in an energetically stable conformation binds to a pocket of CD3ε that is not hidden by either CD3γ or CD3δ. Lastly, magnetic microbeads conjugated with the synthesized peptide ligands showed a weak but specific association with Jurkat cells and induced the calcium flux, a hallmark indication of proximal T cell receptor signaling, which gave rise to an enhancement of IL-2 section and cell proliferation. The novel peptide ligand and its various multivalent forms have a great potential in applications related to T cell biology and T cell immunotherapy.
Keywords	B-cell lymphoma ; T-lymphocytes ; antigens ; bacteriophages ; calcium ; cell proliferation ; dose response ; humans ; immunotherapy ; interleukin-2 ; ligands ; magnetism ; microbeads ; peptide libraries
Language	English
Dates of publication	2021-0219
Size	p. 1661-1675.
Publishing place	The Royal Society of Chemistry
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2702241-9
ISSN	2050-7518 ; 2050-750X
ISSN (online)	2050-7518
ISSN	2050-750X
DOI	10.1039/d0tb02235g
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Wet-spinnability and crosslinked Fiber properties of alginate/hydroxyethyl cellulose with varied proportion for potential use in tendon tissue engineering

Hojabri, Mahsa / Tayebi, Tahereh / Kasravi, Mohammadreza / Aghdaee, Amirhossein / Ahmadi, Armin / Mazloomnejad, Radman / Tarasi, Roghayeh / Shaabani, Alireza / Bahrami, Soheyl / Niknejad, Hassan

International Journal of Biological Macromolecules. 2023 Apr. 17, p.124492-

2023 , Page(s) 124492–

Abstract	Researchers have examined different bio-inspired materials in tissue engineering and regenerative medicine to fabricate scaffolds to address tendon regeneration requirements. We developed fibers based on alginate (Alg) and hydroxyethyl cellulose (HEC) by wet-spinning technique to mimic the fibrous sheath of ECM. Various proportions (25:75, 50:50, 75:25) of 1 % Alg and 4 % HEC were blended to this aim. Two steps of crosslinking with different concentrations of CaCl₂ (2.5 and 5 %) and glutaraldehyde (2.5 %) were used to improve physical and mechanical properties. The fibers were characterized by FTIR, SEM, swelling, degradation, and tensile tests. The in vitro proliferation, viability, and migration of tenocytes on the fibers were also evaluated. Moreover, the biocompatibility of implanted fibers was investigated in an animal model. The results showed ionic and covalent molecular interactions between the components. In addition, by properly maintaining surface morphology, fiber alignment, and swelling, lower concentrations of HEC in the blending provided good degradability and mechanical features. The mechanical strength of fibers was in the range of collagenous fibers. Increasing the crosslinking led to significantly different mechanical behaviors in terms of tensile strength and elongation at break. Because of good in vitro and in vivo biocompatibility, tenocyte proliferation, and migration, the biological macromolecular fibers could serve as desirable tendon substitutes. This study provides more practical insight into tendon tissue engineering in translational medicine.
Keywords	alginates ; animal models ; biocompatibility ; cellulose ; crosslinking ; glutaraldehyde ; medicine ; tenocytes ; tensile strength ; translational medical research ; viability ; Wet-spinning ; Tissue engineering ; Tendon ; Alginate ; Hydroxyethylcellulose
Language	English
Dates of publication	2023-0417
Publishing place	Elsevier B.V.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2023.124492
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