Domesticating the foreign body response: recent advances and applications
Open accessAbstract
The foreign body response is an immunological process that leads to the rejection of implanted devices and presents a fundamental challenge to their performance, durability, and therapeutic utility. Recent advances in materials development and device design are now providing strategies to overcome this immune-mediated reaction. Here, we briefly review our current mechanistic understanding of the foreign body response and highlight new anti-FBR technologies from this decade that have been applied successfully in biomedical applications relevant to implants, devices, and cell-based therapies. Further development of these important technologies promises to enable new therapies, diagnostics, and revolutionize the management of patient care for many intractable diseases.
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Following insertion of synthetic scaffolds into the human body, the immune system establishes the foreign body response (FBR), initiated by migration of neutrophils and macrophages and followed by production of inflammatory cytokines at the implantation site.
“Following the insertion of synthetic scaffolds into the human body, the immune system establishes the foreign body response (FBR), initiated by the migration of neutrophils and macrophages and followed by the production of inflammatory cytokines at the implantation site [22].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [22]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredMost synthetic grafts are covered with a dense fibrotic capsule and isolated from the human body.
“Consequently, most synthetic grafts are covered with a dense fibrotic capsule and isolated from the human body.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [22]
The Review of the Foreign Body Response describes fibrotic capsules forming around implants, and the Surface Topography section reports encapsulation of uncoated tissue expanders in a non-human primate model. These passages support fibrotic encapsulation as a problem, but they do not establish that most synthetic grafts develop a dense capsule or are isolated from the human body. (LLM, conf=0.83)
Experimental — accuracy not yet measuredProteins from blood and serum are adsorbed on the scaffold surface, activating the coagulation pathway and leading to the formation of a temporary matrix.
“Simultaneously, proteins from blood and serum are adsorbed on the scaffold surface, activating the coagulation pathway and leading to the formation of a temporary matrix [205].”
From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [205]
The Review of the Foreign Body Response section (page unavailable) describes early protein adsorption on implanted biomaterial surfaces, including adsorption of the plasma protein fibrinogen. It does not state that this adsorption activates the coagulation pathway or forms a temporary matrix; searches for those terms and “provisional matrix” found no supporting passage. (LLM, conf=0.85)
Experimental — accuracy not yet measuredImplantation of the scaffold causes iatrogenic injury resulting in the onset of the acute inflammatory reaction.
“At first, implantation of the scaffold causes iatrogenic injury resulting in the onset of the acute inflammatory reaction.”
From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [205]
The Review of the Foreign Body Response section (page unavailable) describes inflammation beginning soon after implantation, with neutrophils appearing at the implant site within hours. It also links inflammation to signals released from damaged tissue, but does not specifically state that scaffold implantation causes iatrogenic injury that initiates the acute reaction. (LLM, conf=0.83)
Experimental — accuracy not yet measuredAccumulated fibrinogen is the main initiator of the acute inflammatory phase.
“This matrix is placed around and on the scaffold, and research confirmed that accumulated fibrinogen is the main initiator of the acute inflammatory phase.”
From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [205]
The Review of the Foreign Body Response section says fibrinogen is a prominent protein adsorbed to implants and has been shown to promote inflammation after surface deposition. It does not identify accumulated fibrinogen as the main initiator of the acute inflammatory phase; it also discusses other adsorbed proteins that may initiate immune processes. (LLM, conf=0.87)
Experimental — accuracy not yet measured
This stage is also characterized by the recruitment of neutrophils and by the release of the cytokines IL-4 and IL-13 from the mast cells.
“This stage is also characterized by the recruitment of neutrophils and by the release of the cytokines IL-4 and IL-13 from the mast cells.”
From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [205]
The Review of the Foreign Body Response section (page not available) says neutrophils appear at the implantation site within hours and predominate for the first two days, supporting their recruitment during the early response. The passages found do not say that mast cells release IL-4 or IL-13, so that part of the claim is unsupported. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe range of their concentration influences the extent and onset of the FBR.
“The range of their concentration influences the extent and onset of the FBR [205].”
From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [205]
The Review of the Foreign Body Response (page unavailable) says that TGF-β, IL-1, and TNF-α are important in foreign body giant-cell formation and occur at high concentrations around implants. It does not say that variation in their concentrations determines the extent or onset of the FBR. (LLM, conf=0.72)
Experimental — accuracy not yet measuredAdjacent capillaries dilate, and cytokines together with damage-associated molecular patterns (DAMPs) are released from platelets, damaged cells, and ECM.
“Adjacent capillaries dilate, and cytokines together with damage-associated molecular patterns (DAMPs) are released from platelets, damaged cells, and ECM.”
From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [205]
The Review of the Foreign Body Response (FBR) says that endogenous structures are released from damaged tissue and that infiltrating monocytes secrete cytokines. It does not describe adjacent capillaries dilating or establish that platelets, damaged cells, and ECM release the stated combination of cytokines and DAMPs. (LLM, conf=0.84)
Experimental — accuracy not yet measuredFBR remains as long as the graft is fully degraded or removed; otherwise, chronic inflammation may occur.
“FBR remains as long as the graft is fully degraded or removed; otherwise, chronic inflammation may occur [22, 24].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [22]
Devices made of biodegradable and bioresorbable materials have been increasingly gathering momentum as a viable class of bioelectronics to minimize effect of FBR when implanted.
“Apart from surface modification or adjusting the invasiveness of the implants, devices made of biodegradable and bioresorbable materials have been increasingly gathering momentum as a viable class of bioelectronics to minimize the effect of FBR when implanted (Veiseh and Vegas, 2019) (Figure 6).”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Veiseh and Vegas, 2019
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Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics
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“Apart from surface modification or adjusting the invasiveness of the implants, devices made of biodegradable and bioresorbable materials have been increasingly gathering momentum as a viable class of bioelectronics to minimize the effect of FBR when implanted (Veiseh and Vegas, 2019) (Figure 6).”
BackgroundKasravi, M., Ahmadi, A., Babajani, A., Mazloomnejad, R., Hatamnejad, M. R., Shariatzadeh, S., Bahrami, S., & Niknejad, H. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00348-z · Cited by 316 · see citing works
“FBR remains as long as the graft is fully degraded or removed; otherwise, chronic inflammation may occur [22, 24].”
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Investigating Immunomodulatory Biomaterials for Preventing the Foreign Body Response
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Engineered stem cells by emerging biomedical stratagems
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- Authors
- Veiseh, O., & Vegas, A. J.
- Affiliations
- Boston University (US)
- Corresponding author
- Vegas, Arturo J.
- ORCID
- Vegas, Arturo J.
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 144
- Pages
- 148-161
- ISSN
- 0169-409X (ISSN-L)
- PMC
- PMC6774350
- OpenAlex
- W2971483210
- Cited by
- 245
- References
- 125
- Citations by year
- 2026: 45 · 2025: 41 · 2024: 46 · 2023: 42 · 2022: 33 · 2021: 26 · 2020: 12
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Advanced Drug Delivery Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Prevention and Research Institute of Texas
- National Institutes of Health
- Juvenile Diabetes Research Foundation United States of America
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Surgery › Orthopaedic implants and arthroplasty
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- foreign body reaction, implant rejection, biomaterials, implant design, cell therapy, biocompatibility, device durability
- MeSH terms
- Animals, Equipment and Supplies, Foreign-Body Reaction, Humans, Prostheses and Implants
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