Bio-inspired poly-DL-serine materials resist the foreign-body response

AbstractImplantation-caused foreign-body response (FBR) is a commonly encountered issue and can result in failure of implants. The high L-serine content in low immunogenic silk sericin, and the high D-serine content as a neurotransmitter together inspire us to prepare poly-DL-serine (PSer) materials in mitigating the FBR. Here we report highly water soluble, biocompatible and easily accessible PSer hydrogels that cause negligible inflammatory response after subcutaneous implantation in mice for 1 week and 2 weeks. No obvious collagen capsulation is found surrounding the PSer hydrogels after 4 weeks, 3 months and 7 months post implantation. Histological analysis on inflammatory cytokines and RNA-seq assay both indicate that PSer hydrogels show low FBR, comparable to the Mock group. The anti-FBR performance of PSer hydrogels at all time points surpass the poly(ethyleneglycol) hydrogels that is widely utilized as bio-inert materials, implying the potent and wide application of PSer materials in implantable biomaterials and biomedical devices.

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Mechanically Matched Silicone Brain Implants Reduce Brain Foreign Body Response

10.1101/2020.12.13.422566 ◽

2020 ◽

Author(s):

Edward Zhang ◽

Alia Alameri ◽

Jean-Pierre Clement ◽

Andy Ng ◽

Timothy E Kennedy ◽

...

Keyword(s):

Foreign Body ◽

Neurological Disorders ◽

Foreign Body Response ◽

Brain Implants ◽

Rat Neocortex ◽

The Brain ◽

Post Implantation ◽

Body Response ◽

Clinical Adoption

Brain implants are increasingly used to treat neurological disorders and diseases. However, the brain foreign body response (FBR) elicited by implants affects neuro-electrical transduction and long-term reliability limiting their clinical adoption. The mismatch in Young's modulus between silicon implants (~180 GPa) and brain tissue (~1-30 kPa) exacerbates the FBR resulting in the development of flexible implants from polymers such as polyimide (~1.5-2.5 GPa). However, a stiffness mismatch of at least two orders of magnitude remains. Here, we introduce (i) the first mechanically matched brain implant (MMBI) made from silicone (~20 kPa), (ii) new microfabrication methods, and (iii) a novel dissolvable sugar shuttle to reliably implant MMBIs. MMBIs were fabricated via vacuum-assisted molding using sacrificial sugar molds and were then encased in sugar shuttles that dissolved within 2 min after insertion into rat brains. Sections of rat neocortex implanted with MMBIs, PDMS implants, and silicon implants were analyzed by immunohistochemistry 3 and 9-weeks post-implantation. MMBIs resulted in significantly higher neuronal density and lower FBR within 50 μm of the tissue-implant interface compared to PDMS and silicon implants suggesting that materials mechanically matched to brain further minimize the FBR and could contribute to better implant functionality and long-term reliability.

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Biocompatibility of Subcutaneously Implanted Plant-Derived Cellulose Biomaterials

10.1101/039644 ◽

2016 ◽

Author(s):

Daniel J. Modulevsky ◽

Charles M. Cuerrier ◽

Andrew E. Pelling

Keyword(s):

Immune Response ◽

Histological Analysis ◽

Foreign Body Response ◽

Wild Type ◽

Fibroblast Migration ◽

Potential Applications ◽

Males And Females ◽

Immunocompetent Mice ◽

Post Implantation ◽

Body Response

ABSTRACTThere is intense interest in developing novel biomaterials which support the invasion and proliferation of living cells for potential applications in tissue engineering and regenerative medicine. Decellularization of existing tissues have formed the basis of one major approach to producing 3D scaffolds for such purposes. In this study, we utilize the native hypanthium tissue of apples and a simple preparation methodology to create implantable cellulose scaffolds. To examine biocompatibility, scaffolds were subcutaneously implanted in wild-type, immunocompetent mice (males and females; 6-9 weeks old). Following the implantation, the scaffolds were resected at 1, 4 and 8 weeks and processed for histological analysis (H&E, Masson’s Trichrome, anti-CD31 and anti-CD45 antibodies). Histological analysis revealed a characteristic foreign body response to the scaffold 1 week post-implantation. However, the immune response was observed to gradually disappear by 8 weeks post-implantation. By 8 weeks, there was no immune response in the surrounding dermis tissue and active fibroblast migration within the cellulose scaffold was observed. This was concomitant with the deposition of a new collagen extracellular matrix. Furthermore, active blood vessel formation within the scaffold was observed throughout the period of study indicating the pro-angiogenic properties of the native scaffolds. Finally, while the scaffolds retain much of their original shape they do undergo a slow deformation over the 8-week length of the study. Taken together, our results demonstrate that native cellulose scaffolds are biocompatible and exhibit promising potential as a surgical biomaterial.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22041708 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1708

Author(s):

Saeedeh Darzi ◽

Kallyanashis Paul ◽

Shanilka Leitan ◽

Jerome A. Werkmeister ◽

Shayanti Mukherjee

Keyword(s):

Tissue Engineering ◽

Foreign Body ◽

Scientific Evidence ◽

Aloe Vera ◽

Material Design ◽

Foreign Body Response ◽

The Body ◽

Design Strategies ◽

Immunomodulatory Effects ◽

Body Response

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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