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2025
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| Online Access: | https://doi.org/10.5281/zenodo.15553206 |
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| author | Hussam Aldeen Mohamed Ibrahim Ahmed Eman Omer Elsiddig Elimam |
| author_facet | Hussam Aldeen Mohamed Ibrahim Ahmed Eman Omer Elsiddig Elimam |
| contents | Rejection of bone grafts is a huge concern in orthopaedic surgery because of the immune responses that affect graft integration, which leads to compromised outcomes. Although many advances in biomaterial design and immunosuppressant management improved the outcomes, many grafts are still rejected due to host immune activation. Various recent studies propose that the gut microbiome, which already impacts immune development and tolerance, can influence and affect systemic immune responses. This review explore a new concept: using patient-derived gut microbial biofilms to camouflage bone grafts, mimicking the mucosal immune interface, decreasing immunogenicity, and possibly aiding with increasing graft acceptance rates. We conducted a review using various resources such as SCOPUS, Web of Science, PubMed, and other scientific databases. We used keywords including, but not limited to, Gut–Bone Axis, Bone Graft, Gut Microbiome, Biofilm Engineering, Microbiome-based Immunotherapy. We included various types of preclinical and clinical studies, experimental and descriptive. Multiple studies selected focused on germ-free models, microbiome signalling pathways, and how probiotics can be used pre-operatively to assist in improving outcomes. The data was collected and analysed to identify potential mechanisms and gaps in studies relevant to microbial biofilms in graft engineering. This review sheds the light on the connection between the microbiome and immune modulation. Germ-free and antibiotic-treated animals showed a significantly decreased foreign body response and improved tolerance to biomaterials. This emphasizes the role of microbial hints in shaping out immunity. Commensal-derived metabolites, like short-chain fatty acids, and microbial peptides, promote regulatory T-cell activity, suppress pro-inflammatory cytokines, and modulate dendritic cell functions. Not only that but, these immunology studies showed that host tolerance is partially maintained by microbial biofilms, as they form a non-inflammatory interface with epithelial barriers, similar to mucosal immunity. We suggest coating bone grafts with patient-derived sterilized biofilms, obtained from colonoscopy samples taken directly from the colon through biopsy (not fecal samples, as the colon contains the adherent mucosal microbiota but the fecal samples contain luminal microbes, and many of them are not adherent or immunologically active at the mucosal surface). This strategy may support native immune mechanisms and reduce the need for systemic immunosuppressants. Recent work on probiotic-infused scaffolds and engineered microbiomes further supports the feasibility of this approach. Furthermore, studies on animals showed the potential of supplementing patients with probiotics before colonoscopies for more optimal culture on the biofilm. The gut–bone immune axis presents a promising possibility for increasing graft acceptance rates using microbiome-based strategies. Engineering bone grafts with personalized, patient-specific microbial biofilms, referred to throughout this review as "microbial camouflage", could shift the focus from passive material compatibility to active immunological compatibility. Future studies should focus on researching the possibility of biofilm extraction using colon biopsies, optimizing sterilization techniques and lab techniques to isolate desired cultures while maintaining immune integrity, and lastly evaluating integration in animal models. If successful, this approach may reshape the way we view biocompatibility, offering a promising intervention for trauma and graft patients. |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_15553206 |
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| publishDate | 2025 |
| publisher | Zenodo |
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| spellingShingle | Microbial Camouflage: Engineering the Gut–Bone Axis for Graft Acceptance Hussam Aldeen Mohamed Ibrahim Ahmed Eman Omer Elsiddig Elimam Rejection of bone grafts is a huge concern in orthopaedic surgery because of the immune responses that affect graft integration, which leads to compromised outcomes. Although many advances in biomaterial design and immunosuppressant management improved the outcomes, many grafts are still rejected due to host immune activation. Various recent studies propose that the gut microbiome, which already impacts immune development and tolerance, can influence and affect systemic immune responses. This review explore a new concept: using patient-derived gut microbial biofilms to camouflage bone grafts, mimicking the mucosal immune interface, decreasing immunogenicity, and possibly aiding with increasing graft acceptance rates. We conducted a review using various resources such as SCOPUS, Web of Science, PubMed, and other scientific databases. We used keywords including, but not limited to, Gut–Bone Axis, Bone Graft, Gut Microbiome, Biofilm Engineering, Microbiome-based Immunotherapy. We included various types of preclinical and clinical studies, experimental and descriptive. Multiple studies selected focused on germ-free models, microbiome signalling pathways, and how probiotics can be used pre-operatively to assist in improving outcomes. The data was collected and analysed to identify potential mechanisms and gaps in studies relevant to microbial biofilms in graft engineering. This review sheds the light on the connection between the microbiome and immune modulation. Germ-free and antibiotic-treated animals showed a significantly decreased foreign body response and improved tolerance to biomaterials. This emphasizes the role of microbial hints in shaping out immunity. Commensal-derived metabolites, like short-chain fatty acids, and microbial peptides, promote regulatory T-cell activity, suppress pro-inflammatory cytokines, and modulate dendritic cell functions. Not only that but, these immunology studies showed that host tolerance is partially maintained by microbial biofilms, as they form a non-inflammatory interface with epithelial barriers, similar to mucosal immunity. We suggest coating bone grafts with patient-derived sterilized biofilms, obtained from colonoscopy samples taken directly from the colon through biopsy (not fecal samples, as the colon contains the adherent mucosal microbiota but the fecal samples contain luminal microbes, and many of them are not adherent or immunologically active at the mucosal surface). This strategy may support native immune mechanisms and reduce the need for systemic immunosuppressants. Recent work on probiotic-infused scaffolds and engineered microbiomes further supports the feasibility of this approach. Furthermore, studies on animals showed the potential of supplementing patients with probiotics before colonoscopies for more optimal culture on the biofilm. The gut–bone immune axis presents a promising possibility for increasing graft acceptance rates using microbiome-based strategies. Engineering bone grafts with personalized, patient-specific microbial biofilms, referred to throughout this review as "microbial camouflage", could shift the focus from passive material compatibility to active immunological compatibility. Future studies should focus on researching the possibility of biofilm extraction using colon biopsies, optimizing sterilization techniques and lab techniques to isolate desired cultures while maintaining immune integrity, and lastly evaluating integration in animal models. If successful, this approach may reshape the way we view biocompatibility, offering a promising intervention for trauma and graft patients. |
| title | Microbial Camouflage: Engineering the Gut–Bone Axis for Graft Acceptance |
| url | https://doi.org/10.5281/zenodo.15553206 |