Immunobiology and Application of Aloe vera-Based Scaffolds in Tissue Engineering

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.

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Mesenchymal stem cell-based bioengineered constructs: foreign body response, cross-talk with macrophages and impact of biomaterial design strategies for pelvic floor disorders

Interface Focus ◽

10.1098/rsfs.2018.0089 ◽

2019 ◽

Vol 9 (4) ◽

pp. 20180089 ◽

Cited By ~ 18

Author(s):

Shayanti Mukherjee ◽

Saeedeh Darzi ◽

Kallyanashis Paul ◽

Jerome A. Werkmeister ◽

Caroline E. Gargett

Keyword(s):

Foreign Body ◽

Pelvic Floor ◽

Critical Role ◽

Pelvic Organ ◽

Foreign Body Response ◽

Design Strategies ◽

Macrophage Response ◽

Improved Outcomes ◽

Key Aspects ◽

Body Response

An excessive foreign body response (FBR) has contributed to the adverse events associated with polypropylene mesh usage for augmenting pelvic organ prolapse surgery. Consequently, current biomaterial research considers the critical role of the FBR and now focuses on developing better biocompatible biomaterials rather than using inert implants to improve the clinical outcomes of their use. Tissue engineering approaches using mesenchymal stem cells (MSCs) have improved outcomes over traditional implants in other biological systems through their interaction with macrophages, the main cellular player in the FBR. The unique angiogenic, immunomodulatory and regenerative properties of MSCs have a direct impact on the FBR following biomaterial implantation. In this review, we focus on key aspects of the FBR to tissue-engineered MSC-based implants for supporting pelvic organs and beyond. We also discuss the immunomodulatory effects of the recently discovered endometrial MSCs on the macrophage response to new biomaterials designed for use in pelvic floor reconstructive surgery. We conclude with a focus on considerations in biomaterial design that take into account the FBR and will likely influence the development of the next generation of biomaterials for gynaecological applications.

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Interleukin 17 and senescent cells regulate the foreign body response to synthetic material implants in mice and humans

Science Translational Medicine ◽

10.1126/scitranslmed.aax3799 ◽

2020 ◽

Vol 12 (539) ◽

pp. eaax3799 ◽

Cited By ~ 6

Author(s):

Liam Chung ◽

David R. Maestas ◽

Andriana Lebid ◽

Ashlie Mageau ◽

Gedge D. Rosson ◽

...

Keyword(s):

T Cells ◽

Foreign Body ◽

Foreign Body Response ◽

The Body ◽

Lymphoid Cells ◽

Interleukin 17 ◽

Synthetic Material ◽

T Helper 17 ◽

Synthetic Materials ◽

Body Response

Medical devices and implants made of synthetic materials can induce an immune-mediated process when implanted in the body called the foreign body response, which results in formation of a fibrous capsule around the implant. To explore the immune and stromal connections underpinning the foreign body response, we analyzed fibrotic capsules surrounding surgically excised human breast implants from 12 individuals. We found increased numbers of interleukin 17 (IL17)–producing γδ+ T cells and CD4+ T helper 17 (TH17) cells as well as senescent stromal cells in the fibrotic capsules. Further analysis in a murine model demonstrated an early innate IL17 response to implanted synthetic material (polycaprolactone) particles that was mediated by innate lymphoid cells and γδ+ T cells. This was followed by a chronic adaptive CD4+ TH17 cell response that was antigen dependent. Synthetic materials with varying chemical and physical properties implanted either in injured muscle or subcutaneously induced similar IL17 responses in mice. Mice deficient in IL17 signaling established that IL17 was required for the fibrotic response to implanted synthetic materials and the development of p16INK4a senescent cells. IL6 produced by senescent cells was sufficient for the induction of IL17 expression in T cells. Treatment with a senolytic agent (navitoclax) that killed senescent cells reduced IL17 expression and fibrosis in the mouse implant model. Discovery of a feed-forward loop between the TH17 immune response and the senescence response to implanted synthetic materials introduces new targets for therapeutic intervention in the foreign body response.

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Tailoring the Foreign Body Response for In Situ Vascular Tissue Engineering

Tissue Engineering Part C Methods ◽

10.1089/ten.tec.2014.0264 ◽

2015 ◽

Vol 21 (5) ◽

pp. 436-446 ◽

Cited By ~ 15

Author(s):

Tonia C. Rothuizen ◽

Febriyani F.R. Damanik ◽

James M. Anderson ◽

Tom Lavrijsen ◽

Martijn A.J. Cox ◽

...

Keyword(s):

Tissue Engineering ◽

Foreign Body ◽

Vascular Tissue ◽

Foreign Body Response ◽

Vascular Tissue Engineering ◽

Body Response

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

Journal of Biomaterials Applications ◽

10.1177/0885328216687664 ◽

2017 ◽

Vol 31 (7) ◽

pp. 1077-1086 ◽

Cited By ~ 3

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.

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Beneficial effects of hydrocortisone or spironolactone coating on foreign body response to mesh biomaterial in a mouse model

Journal of Biomedical Materials Research Part A ◽

10.1002/jbm.a.33136 ◽

2011 ◽

Vol 99A (3) ◽

pp. 335-343 ◽

Cited By ~ 16

Author(s):

Christopher J. Brandt ◽

Daniel Kammer ◽

Anette Fiebeler ◽

Uwe Klinge

Keyword(s):

Foreign Body ◽

Mouse Model ◽

Foreign Body Response ◽

Beneficial Effects ◽

Body Response

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Mitigating the foreign body response through ‘immune-instructive’ biomaterials

Journal of Immunology and Regenerative Medicine ◽

10.1016/j.regen.2021.100040 ◽

2021 ◽

Vol 12 ◽

pp. 100040

Author(s):

Lisa Kämmerling ◽

Leanne E. Fisher ◽

Ezgi Antmen ◽

Gorkem M. Simsek ◽

Hassan M. Rostam ◽

...

Keyword(s):

Foreign Body ◽

Foreign Body Response ◽

Body Response

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A Polymer-Biologic Hybrid Hernia Construct: Review of Data and Early Experiences

Polymers ◽

10.3390/polym13121928 ◽

2021 ◽

Vol 13 (12) ◽

pp. 1928

Author(s):

Michael Sawyer ◽

Stephen Ferzoco ◽

George DeNoto

Keyword(s):

Foreign Body ◽

Hernia Repair ◽

Surgical Mesh ◽

Foreign Body Response ◽

Host Cells ◽

Mesh Reinforcement ◽

Decellularized Extracellular Matrix ◽

Early Experiences ◽

Tissue Matrix ◽

Body Response

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.

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