scholarly journals Decellularized Dermis Extracellular Matrix Alloderm as a Scaffold for Biological Engineered Blood Vessels

2020 ◽  
Author(s):  
Bijal Patel ◽  
Dan Saliganan ◽  
Ali Rteil ◽  
Loay Kabbani ◽  
Mai Lam
Keyword(s):  
Extracellular Matrix ◽  
Blood Vessels ◽  
Tissue Mechanics ◽  
Foreign Body Response ◽  
Mechanical Conditioning ◽  
Fiber Maturity ◽  
Tissue Rejection ◽  
Decellularized Dermis ◽  
Body Response ◽  
The Ideal

Abstract The ideal engineered vascular graft would utilize human-derived materials to minimize foreign body response and tissue rejection. Current biological engineered blood vessels (BEBVs) inherently lack the structure required for implantation. Current methods of mechanical conditioning to encourage extracellular matrix (ECM) deposition requires weeks to months, impeding translation. We hypothesized that an ECM scaffold would provide the structure needed. Skin dermis ECM is commonly used in reconstructive surgeries, is commercially available and is FDA-approved. We evaluated the commercially available decellularized skin dermis ECM called Alloderm for its efficacy in providing structure to biological engineered blood vessels. Alloderm was seeded with fibroblast cells typically found in the adventitia during integration into our lab’s unique protocol for generating BEBVs. To assess structure, tissue mechanics were analyzed. Standard BEBVs without Alloderm exhibited a tensile strength of 67.9 ± 9.78 kPa, whereas Alloderm integrated BEBVs showed a significant increase in strength to 1500 ± 334 kPa. In comparison, native vessel strength is 1430 ± 604 kPa. Burst pressure reached 51.3 ± 2.19 mmHg. Total collagen and fiber maturity were significantly increased due to the presence of the scaffolding material. These results demonstrate the success of Alloderm to provide structure to BEBVs in an effective way.

scholarly journals Decellularized dermis extracellular matrix alloderm mechanically strengthens biological engineered tunica adventitia-based blood vessels

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bijal Patel ◽  
Bryan T. Wonski ◽  
Dan M. Saliganan ◽  
Ali Rteil ◽  
Loay S. Kabbani ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Structural Integrity ◽  
Tissue Mechanics ◽  
Foreign Body Response ◽  
Low Probability ◽  
Fiber Maturity ◽  
Tissue Rejection ◽  
Decellularized Dermis ◽  
Body Response ◽  
The Ideal

AbstractThe ideal engineered vascular graft would utilize human-derived materials to minimize foreign body response and tissue rejection. Current biological engineered blood vessels (BEBVs) inherently lack the structure required for implantation. We hypothesized that an ECM material would provide the structure needed. Skin dermis ECM is commonly used in reconstructive surgeries, is commercially available and FDA-approved. We evaluated the commercially-available decellularized skin dermis ECM Alloderm for efficacy in providing structure to BEBVs. Alloderm was incorporated into our lab’s unique protocol for generating BEBVs, using fibroblasts to establish the adventitia. To assess structure, tissue mechanics were analyzed. Standard BEBVs without Alloderm exhibited a tensile strength of 67.9 ± 9.78 kPa, whereas Alloderm integrated BEBVs showed a significant increase in strength to 1500 ± 334 kPa. In comparison, native vessel strength is 1430 ± 604 kPa. Burst pressure reached 51.3 ± 2.19 mmHg. Total collagen and fiber maturity were significantly increased due to the presence of the Alloderm material. Vessels cultured for 4 weeks maintained mechanical and structural integrity. Low probability of thrombogenicity was confirmed with a negative platelet adhesion test. Vessels were able to be endothelialized. These results demonstrate the success of Alloderm to provide structure to BEBVs in an effective way.

scholarly journals Polypropylene surgical mesh coated with extracellular matrix mitigates the host foreign body response

2013 ◽  
Vol 102 (1) ◽  
pp. 234-246 ◽  
Author(s):  
Matthew T. Wolf ◽  
Christopher A. Carruthers ◽  
Christopher L. Dearth ◽  
Peter M. Crapo ◽  
Alexander Huber ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Foreign Body ◽  
Surgical Mesh ◽  
Foreign Body Response ◽  
Body Response

scholarly journals Assessing the Effects of VEGF Releasing Microspheres on the Angiogenic and Foreign Body Response to a 3D Printed Silicone-Based Macroencapsulation Device

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2077
Author(s):  
Ruth E. Levey ◽  
Fergal B. Coulter ◽  
Karina C. Scheiner ◽  
Stefano Deotti ◽  
Scott T. Robinson ◽  
...  
Keyword(s):  
Foreign Body ◽  
Blood Vessels ◽  
Foreign Body Response ◽  
Islet Cell Transplantation ◽  
Clinical Implementation ◽  
Multi Scale ◽  
Significant Difference ◽  
Body Response

Macroencapsulation systems have been developed to improve islet cell transplantation but can induce a foreign body response (FBR). The development of neovascularization adjacent to the device is vital for the survival of encapsulated islets and is a limitation for long-term device success. Previously we developed additive manufactured multi-scale porosity implants, which demonstrated a 2.5-fold increase in tissue vascularity and integration surrounding the implant when compared to a non-textured implant. In parallel to this, we have developed poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymer microspheres containing VEGF, which exhibited continued release of bioactive VEGF for 4-weeks in vitro. In the present study, we describe the next step towards clinical implementation of an islet macroencapsulation device by combining a multi-scale porosity device with VEGF releasing microspheres in a rodent model to assess prevascularization over a 4-week period. An in vivo estimation of vascular volume showed a significant increase in vascularity (* p = 0.0132) surrounding the +VEGF vs. −VEGF devices, however, histological assessment of blood vessels per area revealed no significant difference. Further histological analysis revealed significant increases in blood vessel stability and maturity (** p = 0.0040) and vessel diameter size (*** p = 0.0002) surrounding the +VEGF devices. We also demonstrate that the addition of VEGF microspheres did not cause a heightened FBR. In conclusion, we demonstrate that the combination of VEGF microspheres with our multi-scale porous macroencapsulation device, can encourage the formation of significantly larger, stable, and mature blood vessels without exacerbating the FBR.

scholarly journals Regulation of extracellular matrix assembly and structure by hybrid M1/M2 macrophages

2020 ◽  
Author(s):  
Claire E. Witherel ◽  
Kimheak Sao ◽  
Becky K. Brisson ◽  
Biao Han ◽  
Susan W. Volk ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Foreign Body ◽  
Dermal Fibroblasts ◽  
Foreign Body Response ◽  
Conditioned Media ◽  
Proper Function ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Body Response

AbstractAberrant extracellular matrix (ECM) assembly surrounding implanted biomaterials is the hallmark of the foreign body response, in which implants become encapsulated in thick fibrous tissue that prevents their proper function. While macrophages are known regulators of fibroblast behavior, how their phenotype influences ECM assembly and the progression of the foreign body response is poorly understood. In this study, we used in vitro models with physiologically relevant macrophage phenotypes, as well as controlled release of macrophage-modulating cytokines from gelatin hydrogels implanted subcutaneously in vivo to investigate the role of macrophages in ECM assembly. Primary human macrophages were polarized to four distinct phenotypes, which have each been associated with fibrosis, including pro-inflammatory M1, pro-healing M2, and a hybrid M1/M2, generated by exposing macrophages to M1- and M2-promoting stimuli simultaneously. Additionally, macrophages were first polarized to M1 and then to M2 (M1→M2) to generate a phenotype typically observed during normal wound healing. Human dermal fibroblasts that were cultured in macrophage-conditioned media upregulated numerous genes involved in regulation of ECM assembly, especially in M2-conditioned media. Hybrid M1/M2 macrophage-conditioned media caused fibroblasts to produce a matrix with thicker and less aligned fibers, while M2 macrophage-conditioned media caused the formation of a more aligned matrix with thinner fibers. Gelatin methacrylate hydrogels containing interleukin-4 (IL4) and IL13-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were designed to promote the M2 phenotype in a murine subcutaneous in vivo model. NanoString multiplex gene expression analysis of hydrogel explants showed that hydrogels with and without drug caused markers of both M1 and M2 phenotypes to be highly expressed, but the release of IL4+IL13 promoted upregulation of M2 markers and genes associated with regulation of ECM assembly, such as Col5a1 and Col6a1. Biochemical analysis and second harmonic generation microscopy showed that the release of IL4+IL13 increased total sulfated glycosaminoglycan content and decreased fibril alignment, which is typically associated with less fibrotic tissue. Together, these results show that hybrid M1/M2 macrophages regulate ECM assembly, and that shifting the balance towards M2 may promote architectural and compositional changes in ECM with enhanced potential for downstream remodeling.

scholarly journals Towards an in vitro model mimicking the foreign body response: tailoring the surface properties of biomaterials to modulate extracellular matrix

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Febriyani F. R. Damanik ◽  
Tonia C. Rothuizen ◽  
Clemens van Blitterswijk ◽  
Joris I. Rotmans ◽  
Lorenzo Moroni
Keyword(s):  
Extracellular Matrix ◽  
Foreign Body ◽  
Surface Properties ◽  
In Vitro Model ◽  
Foreign Body Response ◽  
Vitro Model ◽  
Body Response

Examinations of a new long-term degradable electrospun polycaprolactone scaffold in three rat abdominal wall models

2017 ◽  
Vol 31 (7) ◽  
pp. 1077-1086 ◽  
Author(s):  
Hanna Jangö ◽  
Søren Gräs ◽  
Lise Christensen ◽  
Gunnar Lose
Keyword(s):  
Pelvic Organ Prolapse ◽  
Foreign Body ◽  
Abdominal Wall ◽  
Muscle Fiber ◽  
Pelvic Organ ◽  
Foreign Body Response ◽  
Heavy Load ◽  
Tissue Construct ◽  
Body Response

Alternative approaches to reinforce native tissue in reconstructive surgery for pelvic organ prolapse are warranted. Tissue engineering combines the use of a scaffold with the regenerative potential of stem cells and is a promising new concept in urogynecology. Our objective was to evaluate whether a newly developed long-term degradable polycaprolactone scaffold could provide biomechanical reinforcement and function as a scaffold for autologous muscle fiber fragments. We performed a study with three different rat abdominal wall models where the scaffold with or without muscle fiber fragments was placed (1) subcutaneously (minimal load), (2) in a partial defect (partial load), and (3) in a full-thickness defect (heavy load). After 8 weeks, no animals had developed hernia, and the scaffold provided biomechanical reinforcement, even in the models where it was subjected to heavy load. The scaffold was not yet degraded but showed increased thickness in all groups. Histologically, we found a massive foreign body response with numerous large giant cells intermingled with the fibers of the scaffold. Cells from added muscle fiber fragments could not be traced by PKH26 fluorescence or desmin staining. Taken together, the long-term degradable polycaprolactone scaffold provided biomechanical reinforcement by inducing a marked foreign-body response and attracting numerous inflammatory cells to form a strong neo-tissue construct. However, cells from the muscle fiber fragments did not survive in this milieu. Properties of the new neo-tissue construct must be evaluated at the time of full degradation of the scaffold before its possible clinical value in pelvic organ prolapse surgery can be evaluated.

Production of Extracellular Matrix Components in Tissue-Engineered Blood Vessels

2006 ◽  
Vol 12 (4) ◽  
pp. 831-842 ◽  
Author(s):  
Sepideh Heydarkhan-Hagvall ◽  
Maricris Esguerra ◽  
Gisela Helenius ◽  
Rigmor Söderberg ◽  
Bengt R. Johansson ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Blood Vessels ◽  
Extracellular Matrix Components ◽  
Tissue Engineered Blood Vessels ◽  
Matrix Components

A Multiscale Approach to Modeling the Passive Mechanical Contribution of Cells in Tissues

2013 ◽  
Author(s):  
Victor K. Lai ◽  
Mohammad F. Hadi ◽  
Robert T. Tranquillo ◽  
Victor H. Barocas
Keyword(s):  
Extracellular Matrix ◽  
Soft Tissues ◽  
Multiscale Model ◽  
Tissue Mechanics ◽  
Multiscale Approach ◽  
Cellular Solids ◽  
Comprehensive Model ◽  
Modeling Framework ◽  
Tissue Biomechanics ◽  
Tensegrity Model

In addition to their obvious biological roles in tissue function, cells often play a significant mechanical role through a combination of passive and active behaviors. Phenomenological and continuum modeling approaches to understand tissue biomechanics have included improved constitutive laws that incorporate anisotropy in the extracellular matrix (ECM) and/or cellular phenomenon, e.g, [1]. The lack of microstructural detail in these models, however, limits their ability to explore the respective contributions and interactions between different components within a tissue. In contrast, structural approaches attempt to understand tissue biomechanics by incorporating microstructural details directly into the model, e.g., the tensegrity model [2], cellular solids models [3], or biopolymer models [4]. Research in our group focuses on developing a comprehensive model to predict the mechanical behavior of soft tissues via a multiscale approach, a technique that allows integration of the microstructural details of different components into the modeling framework. A significant gap in our previous models, however, is the absence of cells. The current work represents an improvement of the multiscale model via the addition of cells, and investigates the passive mechanical contribution of cells to overall tissue mechanics.

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