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The useful agent to have an ideal biological scaffold

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Raziyeh Kheirjou
Raziyeh Kheirjou
Raziyeh Kheirjou
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Jafar - Soleimani Rad at Tabriz University of Medical Sciences
Jafar - Soleimani Rad
Ahad Ferdowsi Khosroshahi at Tabriz University of Medical Sciences
Ahad Ferdowsi Khosroshahi
Leila Roshangar at Tabriz University of Medical Sciences
Leila Roshangar
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Abstract and Figures

Tissue engineering which is applied in regenerative medicine has three basic components: cells, scaffolds and growth factors. This multidisciplinary field can regulate cell behaviors in different conditions using scaffolds and growth factors. Scaffolds perform this regulation with their structural, mechanical, functional and bioinductive properties and growth factors by attaching to and activating their receptors in cells. There are various types of biological extracellular matrix (ECM) and polymeric scaffolds in tissue engineering. Recently, many researchers have turned to using biological ECM rather than polymeric scaffolds because of its safety and growth factors. Therefore, selection the right scaffold with the best properties tailored to clinical use is an ideal way to regulate cell behaviors in order to repair or improve damaged tissue functions in regenerative medicine. In this review we first divided properties of biological scaffold into intrinsic and extrinsic elements and then explain the components of each element. Finally, the types of scaffold storage methods and their advantages and disadvantages are examined.
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FULL LENGTH REVIEW
The useful agent to have an ideal biological scaffold
Raziyeh Kheirjou .Jafar Soleimani Rad .Ahad Ferdowsi Khosroshahi .
Leila Roshangar
Received: 9 April 2020 / Accepted: 3 November 2020 / Published online: 22 November 2020
ÓSpringer Nature B.V. 2020
Abstract Tissue engineering which is applied in
regenerative medicine has three basic components:
cells, scaffolds and growth factors. This multidisci-
plinary field can regulate cell behaviors in different
conditions using scaffolds and growth factors. Scaf-
folds perform this regulation with their structural,
mechanical, functional and bioinductive properties
and growth factors by attaching to and activating their
receptors in cells. There are various types of biological
extracellular matrix (ECM) and polymeric scaffolds in
tissue engineering. Recently, many researchers have
turned to using biological ECM rather than polymeric
scaffolds because of its safety and growth factors.
Therefore, selection the right scaffold with the best
properties tailored to clinical use is an ideal way to
regulate cell behaviors in order to repair or improve
damaged tissue functions in regenerative medicine. In
this review we first divided properties of biological
scaffold into intrinsic and extrinsic elements and then
explain the components of each element. Finally, the
types of scaffold storage methods and their advantages
and disadvantages are examined.
Keywords Tissue engineering Decellularization
Biological scaffold Extracellular matrix Tissue
banking Storage
Introduction
Tissue engineering has appeared in the 1980s. This
multidisciplinary field is applied in regenerative
medicine to help various damaged tissues and organs,
and it is based on using of cells, scaffolds, and
bioactive factors. Scaffolds not only provide a sup-
portive template for cell attachment, but they also
create a biomechanical and physical environment. So
the scaffolds play an active role in the regulation of
cell behaviors (Qiu 2012).
Because of the toxic and inflammatory capacity of
synthetic polymers, which lead to reducing extracel-
lular matrix (ECM) remodeling and growth capacity,
the xeno-or allogeneic tissues are substituted to
biodegradable synthetic scaffolds (Thompson 1992).
The cells of xeno-or allogeneic tissues as biological
scaffolds, are removed, and their ECM remains as
3-dimensioal (3D) structure (Badylak et al. 2009).
These natural ECMs decrease immune and inflamma-
tory response in grafting through decellularization,
and serve as inductive means through their structural
and functional proteins and endogenous growth fac-
tors (Assmann 2013; Badylak et al. 2012).
R. Kheirjou A. F. Khosroshahi
Department of Anatomical Sciences, Faculty of Medicine,
Tabriz University of Medical Sciences, Tabriz, Iran
J. S. Rad L. Roshangar (&)
Stem Cell Research Center, Tabriz University of Medical
Sciences, 33363879 Tabriz, Iran
e-mail: lroshangar@yahoo.com
123
Cell Tissue Bank (2021) 22:225–239
https://doi.org/10.1007/s10561-020-09881-w(0123456789().,-volV)(0123456789().,-volV)
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Development of Polymeric Microparticles for Controlled Release of Bioactive Drugs Using Modified Solution Enhanced Dispersion by Supercritical CO2
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Identification of extractable growth factors from small intestinal submucosa
Article
  • Dec 1997
  • J CELL BIOCHEM
When implanted as a biomaterial for tissue replacement, selected submucosal layers of porcine small intestine induce site‐specific tissue remodeling. Small intestinal submucosa (SIS), as isolated, is primarily an acellular extracellular matrix material. In an attempt to discover the components of small intestinal submucosa which are able to induce this tissue remodeling, the material was extracted and extracts were tested for the ability to stimulate Swiss 3T3 fibroblasts to synthesize DNA and proliferate. Each of the four different extracts of small intestinal submucosa had measurable cell‐stimulating activity when analyzed in both a whole cell proliferation assay (alamarBlue dye reduction) and a DNA synthesis assay ([³H]‐thymidine incorporation). Proteins extracted from SIS with 2 M urea induced activity profiles in the two assays which were very similar to the activity profiles of basic fibroblast growth factor (FGF‐2) in the assays. As well, the changes in cell morphology in response to the extracted proteins mimicked the changes induced by FGF‐2. Neutralization experiments with specific antibodies to this growth factor confirmed the presence of FGF‐2 and indicated that it was responsible for 60% of the fibroblast‐stimulating activity of the urea extract of small intestinal submucosa. Western blot analysis with a monoclonal antibody specific for FGF‐2 detected a reactive doublet at approximately 19 kDa and further confirmed the presence of FGF‐2. Cell stimulating activity of proteins extracted from SIS with 4 M guanidine was neutralized by an antibody specific for transforming growth factor β (TGFβ). Changes in the morphology of the fibroblasts exposed to this extract were nearly identical to changes induced by TGFβ. Although no reactive protein band was detected at 25 kDa in nonreduced western blot analysis, several bands were reactive at higher molecular weight. The identity of this TGFβ‐related component of small intestinal submucosa is unknown. Identification of FGF‐2 and TGFβ‐related activities in SIS, two growth factors known to significantly affect critical processes of tissue development and differentiation, provides the opportunity to further elucidate the mechanisms by which this extracellular matrix biomaterial modulates wound healing and tissue remodeling. J. Cell. Biochem. 67:478–491, 1997. © 1997 Wiley‐Liss, Inc.
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Improving functional re-endothelialization of acellular liver scaffold using REDV cell-binding domain
Article
  • Jul 2018
  • ACTA BIOMATER
Engineering of functional vascularized liver tissues hold great promise in addressing donor organ shortage for transplantation. Whole organ decellularization is a cell removal method that retains the native vascular structures of the organ such that it can be anastomosed with the recipient circulation after recellularization with healthy cells. However, a main hurdle to successful implantation of bioengineered organ is the inability to efficiently re-endothelialize the vasculature with a functional endothelium, resulting in blood clotting which is the primary cause of failure in early transplant studies. Here, we present an efficient approach for enhancing re-endothelialization of decellularized rat liver scaffolds by conjugating the REDV cell-binding domain to improve attachment of endothelial cells (EC) on vascular wall surfaces. In order to facilitate expression and purification of the peptide, REDV was fused with elastin-like peptide (ELP) that confers thermally triggered aggregation behavior to the fusion protein. After validating the adhesive properties of the REDV-ELP peptide, we covalently coupled REDV-ELP to the blood vasculature of decellularized rat livers and seeded EC using perfusion of the portal vein. We showed that REDV-ELP increased cell attachment, spreading and proliferation of EC within the construct resulting in uniform endothelial lining of the scaffold vasculature. We further observed that REDV-ELP conjugation dramatically reduced platelet adhesion and activation. Altogether, our results demonstrate that this method allowed functional re-endothelialization of liver scaffold and show great potential toward the generation of functional bioengineered liver for long-term transplantation. Statement of significance: There is a critical need for novel organ replacement therapies as the grafts for transplantation fall short of demand. Recent advances in tissue engineering, through the use of decellularized scaffolds, have opened the possibility that engineered grafts could be used as substitutes for donor livers. However, successful implantation has been challenged by the inability to create a functional vasculature. Our research study reports a new strategy to increase efficiency of endothelialization by increasing the affinity of the vascular matrix for endothelial cells. We functionalized decellularized liver scaffold using elastin-like peptides grafted with REDV cell binding domain. We showed that REDV-ELP conjugation improve endothelial cell attachment and proliferation within the scaffold, demonstrating the feasibility of re-endothelializing a whole liver vasculature using our technique.
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Acellular dermal matrix scaffolds coated with connective tissue growth factor accelerate diabetic wound healing by increasing fibronectin through PKC signaling pathway
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The regional injection of connective tissue growth factor (CTGF) for diabetic wound healing requires multiple components and results in a substantial loss of its biological activity. Acellular dermal matrix (ADM) scaffolds are optimal candidates for delivering these factors to local ischemic environments. In this study, we explored whether CTGF loaded on ADM scaffolds can enhance fibronectin (FN) expression to accelerate diabetic wound healing via the Protein kinase C (PKC) signaling pathway. The performance of CTGF and CTGF+PKC inhibitor, which were loaded on ADM scaffolds to treat dorsal skin wounds in streptozotocin (STZ)-induced diabetic mice, were evaluated with naked ADM as a control. Wound closure showed that ADM scaffolds loaded with CTGF induced greater diabetic wound healing in the early stage of the wound in diabetic mice. Moreover, ADM scaffolds loaded with CTGF obviously increased the expression of FN both at the mRNA and protein levels, while the expression of FN was significantly reduced in the inhibitor group. Furthermore, the ADM+CTGF group, which produce FN, obviously promoted α-SMA and TGF-ß expression and enhanced neovasculature and collagen synthesis at the wound sites. ADM scaffolds loaded with CTGF+PKC inhibitor delayed diabetic wound healing, indicating that FN expression was mediated by the PKC signaling pathway. Our findings offer new perspectives for the treatment of diabetic wound healing and suggest a rationale for the clinical evaluation of CTGF use in diabetic wound healing.
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Characterization of decellularized ovine small intestine sub-mucosal layer as extracellular matrix based scaffold for tissue engineering
Article
  • Apr 2017
Extracellular matrix-based scaffolds derived from mammalian tissues have been used in tissue engineering applications. Among all the tissues, decellularized small intestine submucosal layer (SIS) has been recently investigated for its exceptional characteristics and biocompatibilities. These investigations have been mainly focused on the decellularized porcine SIS; however, there has not been any report on ovine SIS (OSIS) layer. In this study, OSIS was decellularized and its physical, chemical, and morphological properties were evaluated. Decellularization was carried out using chemical reagents and various physical conditions. The effects of different conditions were evaluated on histological and biomechanical properties, quality of residual DNA, GAPDH gene expression, and biocompatibility. Results revealed satisfactory decellularization of OSIS which could be due to its thin thickness. Mechanical properties, structural form, and glycosaminoglycan contents were preserved in all the decellularized groups. In SDS-treated groups, further cells and DNA residues were removed compared to the groups treated with Triton X-100 only. No toxicity was observed in all treatments, and viability, expansion, and cell proliferation were supported. In conclusion, our results suggest that OSIS decellularized scaffold could be considered as an appropriate biological scaffold for tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017.
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