scholarly journals A unique Thy-1-negative immuno-fibroblast population emerges as a key determinant of fibrotic outcomes to biomaterials

2022 ◽  
Author(s):  
Daniel Abebayehu ◽  
Blaise N. Pfaff ◽  
Grace C. Bingham ◽  
Surabhi Ghatti ◽  
Andrew Miller ◽  
...  

Microporous annealed particle (MAP) hydrogels are an exciting new development in biomaterial design. They regulate innate and acquired immunity which has been linked to their ability to evade normal host-material fibrosis. Yet, resident stromal fibroblasts, not immune cells, are the arbiters of the extracellular matrix assembly that characterizes fibrosis. In other idiopathic fibrotic disorders, a fibroblast subpopulation defined by its loss of cell surface Thy-1 expression is strongly correlated with degree of fibrosis. We have previously shown that Thy-1 is a critical αvβ3 integrin regulator that enables normal fibroblast mechanosensing and here, leveraging non-fibrosing MAP gels, we demonstrate that Thy-1-/- mice mount a robust response to MAP gels that remarkably resembles a classical foreign body response. We further find that within the naive, Thy-1+ fibroblast population exists a distinct and cryptic αSMA+ Thy-1- population that emerges in response to IL-1β and TNFα. Employing single-cell RNA sequencing, we find that IL-1β/TNFα-induced Thy-1- fibroblasts actually consist of two distinct subpopulations, both of which are strongly pro-inflammatory. These findings illustrate the emergence of a unique pro-inflammatory, pro-fibrotic fibroblast subpopulation that is central to material-associated fibrosis likely through amplifying local inflammatory signaling.

2017 ◽  
Vol 31 (7) ◽  
pp. 1077-1086 ◽  
Author(s):  
Hanna Jangö ◽  
Søren Gräs ◽  
Lise Christensen ◽  
Gunnar Lose

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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bijal Patel ◽  
Bryan T. Wonski ◽  
Dan M. Saliganan ◽  
Ali Rteil ◽  
Loay S. Kabbani ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
pp. 100040
Author(s):  
Lisa Kämmerling ◽  
Leanne E. Fisher ◽  
Ezgi Antmen ◽  
Gorkem M. Simsek ◽  
Hassan M. Rostam ◽  
...  

Polymers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 1928
Author(s):  
Michael Sawyer ◽  
Stephen Ferzoco ◽  
George DeNoto

Surgical mesh reinforcement of the human abdominal wall has been found to reduce the chance of recurrence in hernia repairs. While traditionally polymer meshes have been used in hernia repair, alternative mesh options have been engineered to prevent the inflammatory foreign body response invoked by polymers. A reinforced tissue matrix (RTM) mesh has been developed by embedding a polymer within a decellularized extracellular matrix. This combination has been attributed to the recruitment of host cells, a pro-healing response, and attenuation of the foreign body response. This has been observed to lead to the regeneration of functional tissue within the repair site that is reinforced by the polymer to offload abdominal pressures over time. This manuscript presents the review of OviTex, an RTM, in several types of hernia repair. The authors have found that the use of RTM in hernia repair is effective in preventing foreign body response, promoting wound healing, and providing reinforcement to lower the risk of hernia recurrence.


2021 ◽  
Vol 22 (4) ◽  
pp. 1708
Author(s):  
Saeedeh Darzi ◽  
Kallyanashis Paul ◽  
Shanilka Leitan ◽  
Jerome A. Werkmeister ◽  
Shayanti Mukherjee

Aloe vera (AV), a succulent plant belonging to the Liliaceae family, has been widely used for biomedical and pharmaceutical application. Its popularity stems from several of its bioactive components that have anti-oxidant, anti-microbial, anti-inflammatory and even immunomodulatory effects. Given such unique multi-modal biological impact, AV has been considered as a biomaterial for regenerative medicine and tissue engineering applications, where tissue repair and neo-angiogenesis are vital. This review outlines the growing scientific evidence that demonstrates the advantage of AV as tissue engineering scaffolds. We particularly highlight the recent advances in the application of AV-based scaffolds. From a tissue engineering perspective, it is pivotal that the implanted scaffolds strike an appropriate foreign body response to be well-accepted in the body without complications. Herein, we highlight the key cellular processes that regulate the foreign body response to implanted scaffolds and underline the immunomodulatory effects incurred by AV on the innate and adaptive system. Given that AV has several beneficial components, we discuss the importance of delving deeper into uncovering its action mechanism and thereby improving material design strategies for better tissue engineering constructs for biomedical applications.


2014 ◽  
Vol 10 (5) ◽  
pp. 1856-1863 ◽  
Author(s):  
M.N. Avula ◽  
A.N. Rao ◽  
L.D. McGill ◽  
D.W. Grainger ◽  
F. Solzbacher

2010 ◽  
Vol 25 (4) ◽  
pp. 337-341 ◽  
Author(s):  
Neusa Margarida Paulo ◽  
Sonia Maria Malmonge ◽  
Liliana Borges de Menezes ◽  
Flávia Gontijo de Lima ◽  
Aline de Moraes Faria ◽  
...  

PURPOSE: To verify if the composit poli (2-hydroxyethyl methacrylate)-PolyHEMA/polypropylene mesh implanted in the female rat's abdominal wall could be suitable for the prevention of peritoneal adhesions, and for the evaluation of the tecidual response produced by this biomaterial. METHODS: Polypropylene meshes (Group PP, n=20) and polypropylene meshes coated with a layer of poli (2-hydroxyethyl methacrylate)-PolyHEMA (Group PH, n=20) were implanted on the abdominal wall of Wistar female rats. Ten animals from each group were submitted to euthanasia at 15 and 30 days of the postoperative period. RESULTS: The animals from the group PP presented visceral adhesions on the mesh surface, which was not observed in the ones from group PH. At the histopathological examination foreign body response was observed in both groups, whilst there was a greater intensity of inflammatory response in group PH on both moments. CONCLUSION: The poli (2-hydroxyethyl methacrylate) polyHEMA hydrogel associated to polypropylene mesh reduces visceral adhesion formation in rats, although it may be associated to greater inflammatory reaction.


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