journal article·2026-03Open access

Commensal microflora coating endows implants with biofilm-repellent, immunomodulatory and osteogenic properties

Muhammad Imran Rahim, Shehneela Baseer, Daniela Paasch, Matthias Steglich, Syed Fakhar H. Waqas, Nico Lachmann, Christine S. Falk, Meike Stiesch

Acta Biomaterialia· Volume 212

Abstract

Bacteria often form biofilms on biomaterials, and these biomaterial-associated infections then become highly resistant to antibiotics and the host immune system. Biofilm-driven implant failures underscore the urgent need for surface modifications that can concurrently prevent microbial colonization, modulate immune responses, and stimulate bone formation. Considering the competitive and osteo-immunomodulatory properties of commensal microflora, we developed Commensal Hybrid Materials (CHMs) by heat-anchoring multilayer assemblies of beneficial microbes onto titanium surfaces. A firmly adherent, carbon- and phosphorus-rich coating with micro-roughness and near-hydrophobic wettability (θ≈90°) suppressed Porphyromonas gingivalis biofilm formation on implant surfaces ‒ even after human-saliva conditioning. The coating did not release antimicrobial agents or alter bacterial gene expression, thereby avoiding selective pressure for antimicrobial resistance. The coated surfaces were cytocompatible with murine cells, did not elicit an inflammatory response, and skewed macrophages toward an M1-like phenotype with increased reactive oxygen species (ROS) production. Furthermore, CHMs first induced macrophages toward a balanced immune response by promoting pro-inflammatory M1 polarization with elevated TNF-α for infection control, followed by an IL-10-rich anti-inflammatory M2 phenotype that supports tissue repair. This polarization significantly upregulated expression of the osteoinductive factor oncostatin M (OSM), and conditioned media from CHM-stimulated macrophages upregulated type I collagen (Col1) expression in osteoblasts. Coated surfaces supported osteogenic potential in osteoblasts by increasing alkaline phosphatase activity and matrix mineralization. Although forthcoming in vivo studies will further validate performance, these findings position commensal microflora as a single, drug-free coating that integrates biofilm resistance, pro-host immune modulation, and osteogenic support to improve long-term implant outcomes. STATEMENT OF SIGNIFICANCE: Biomaterial-associated infections resist antibiotics and evade host immunity. We engineered commensal hybrid materials (CHMs) by heat-anchoring commensal microflora onto titanium, yielding a drug-free coating that repels biofilms without releasing antimicrobials or perturbing pathogen gene expression, thereby limiting resistance pressure. CHMs modulate macrophages‒eliciting an early M1/TNF-α phenotype for pathogen control followed by an IL-10-rich M2 phase that restores homeostasis. They also increase macrophage oncostatin M (OSM) and enhance osteoblast alkaline phosphatase activity and mineralization, promoting osteogenesis. By uniting biofilm resistance, immune modulation, and osteogenic support on a single surface, CHMs offer a promising route to extend implant longevity in orthopaedics and dentistry.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Bone Tissue Engineering Materials · Gut microbiota and health · Oral microbiology and periodontitis research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (100+)

Show source-provided references
1. Biomaterials for Tissue Engineering10.1002/adem.200700287 ↗
2. Biomaterials and Culture Technologies for Regenerative Therapy of Liver Tissue10.1002/adhm.201600791 ↗
3. Biomaterial-associated infection: locating the finish line in the race for the surface10.1126/scitranslmed.3004528 ↗
4. Survival strategies of infectious biofilms10.1016/j.tim.2004.11.010 ↗
5. Bacterial biofilm and associated infections10.1016/j.jcma.2017.07.012 ↗
6. Bioadhesion in the oral cavity and approaches for biofilm management by surface modifications10.1007/s00784-020-03646-1 ↗
7. Z. Yin, Y. Liu, A. Anniwaer, Y. You, J. Guo, Y. Tang, L. Fu, L. Yi, C. Huang, Rational Designs of Biomaterials for Combating Oral Biofilm Infections, Advanced Materials n/a(n/a) 2305633.
8. Microflora around teeth and dental implants10.4103/1735-3327.95239 ↗
9. Supportive care for the prevention of disease recurrence/progression following peri-implantitis treatment: A systematic review10.1111/jcpe.13822 ↗
10. Epidemiology and risk factors of peri-implantitis: A systematic review10.1111/jre.12562 ↗
11. Peri-implant mucositis and peri-implantitis: key features and differences10.1038/s41415-024-7402-z ↗
12. Peri-Implant Bone Loss and Peri-Implantitis: A Report of Three Cases and Review of the Literature10.1155/2016/2491714 ↗
13. Immune dysregulation and macrophage polarization in peri-implantitis
14. The oralome and its dysbiosis: New insights into oral microbiome-host interactions10.1016/j.csbj.2021.02.010 ↗
15. Antibacterial Coatings: Challenges, Perspectives, and Opportunities10.1016/j.tibtech.2015.09.002 ↗
16. Biomaterial-based antimicrobial therapies for the treatment of bacterial infections10.1038/s41578-021-00362-4 ↗
17. Surface modification strategies to reinforce the soft tissue seal at transmucosal region of dental implants10.1016/j.bioactmat.2024.08.042 ↗
18. Antibacterial infection and immune-evasive coating for orthopedic implants10.1126/sciadv.abb0025 ↗
19. Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing10.1073/pnas.1801013115 ↗
20. Point-of-care antimicrobial coating protects orthopaedic implants from bacterial challenge10.1038/s41467-021-25383-z ↗
21. Implant infections: adhesion, biofilm formation and immune evasion10.1038/s41579-018-0019-y ↗
22. The Slow-Motion Catastrophe of Antimicrobial Resistance and Practical Interventions for All Prescribers10.1016/j.mayocp.2018.11.005 ↗
23. Antibiotic tolerance facilitates the evolution of resistance10.1126/science.aaj2191 ↗
24. Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in Mammalian cells10.1126/scitranslmed.3006055 ↗
25. Tolerance and resistance of microbial biofilms10.1038/s41579-022-00682-4 ↗
26. Bacterial persisters: molecular mechanisms and therapeutic development10.1038/s41392-024-01866-5 ↗
27. Antibiotic-induced inflammation10.1126/scisignal.ade1683 ↗
28. Challenges in linking preclinical anti-microbial research strategies with clinical outcomes for device-associated infections10.22203/eCM.v028a09 ↗
29. Immunomodulatory biomaterials for implant-associated infections: from conventional to advanced therapeutic strategies10.1186/s40824-022-00326-x ↗
30. Combating Implant Infections: Shifting Focus from Bacteria to Host10.1002/adma.202002962 ↗
31. Current Advances in Immunomodulatory Biomaterials for Bone Regeneration10.1002/adhm.201801106 ↗
32. Role of the Commensal Microbiota in Normal and Pathogenic Host Immune Responses10.1016/j.chom.2011.10.004 ↗
33. Oral Biofilms: Pathogens, Matrix, and Polymicrobial Interactions in Microenvironments10.1016/j.tim.2017.09.008 ↗
34. Biogeography of the Oral Microbiome: The Site-Specialist Hypothesis10.1146/annurev-micro-090817-062503 ↗
35. Controlling the human microbiome10.1016/j.cels.2022.12.010 ↗
36. Microbiota-mediated colonization resistance: mechanisms and regulation10.1038/s41579-022-00833-7 ↗
37. The oral microbiota: dynamic communities and host interactions10.1038/s41579-018-0089-x ↗
38. The human oral microbiome10.1128/JB.00542-10 ↗
39. Commensal and Pathogenic Biofilms Alter Toll-Like Receptor Signaling in Reconstructed Human Gingiva10.3389/fcimb.2019.00282 ↗
40. Modulation of host responses by oral commensal bacteria10.3402/jom.v7.26941 ↗
41. Subgingival microbiome in patients with healthy and ailing dental implants
42. Oral microbial communities in sickness and in health10.1016/j.tim.2005.09.006 ↗
43. Oral Commensal Streptococci: Gatekeepers of the Oral Cavity10.1128/jb.00257-22 ↗
44. Commensal Bacteria: An Emerging Player in Defense Against Respiratory Pathogens10.3389/fimmu.2019.01203 ↗
45. Commensal Bacteria Modulate Immunoglobulin A Binding in Response to Host Nutrition10.1016/j.chom.2020.03.012 ↗
46. Exploiting the Oral Microbiome to Prevent Tooth Decay: Has Evolution Already Provided the Best Tools?10.3389/fmicb.2018.03323 ↗
47. A nasal spray with alpha-haemolytic streptococci as long term prophylaxis against recurrent otitis media10.1016/S0165-5876(01)00581-X ↗
48. Effect of recolonisation with "interfering" alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial10.1136/bmj.322.7280.210 ↗
49. Use of Streptococcus salivarius K12 in supporting the mucosal immune function of active young subjects: A randomised double-blind study10.3389/fimmu.2023.1129060 ↗
50. Engineered probiotics biofilm enhances osseointegration via immunoregulation and anti-infection10.1126/sciadv.aba5723 ↗
51. Streptococcus oralis maintains homeostasis in oral biofilms by antagonizing the cariogenic pathogen Streptococcus mutans10.1111/omi.12216 ↗
52. Probiotics Streptococcus salivarius 24SMB and Streptococcus oralis 89a interfere with biofilm formation of pathogens of the upper respiratory tract10.1186/s12879-018-3576-9 ↗
53. In Vitro Effects of Streptococcus oralis Biofilm on Peri-Implant Soft Tissue Cells10.3390/cells9051226 ↗
54. Multilayered Adsorption of Commensal Microflora on Implant Surfaces: an Unconventional and Innovative Method to Prevent Bacterial Infections Associated with Biomaterials
55. Stiesch · 2022
56. Effects of sandblasting and acid etching on the surface properties of additively manufactured and machined titanium and their consequences for osteoblast adhesion under different storage conditions
57. Effect of titanium implants along with silver ions and tetracycline on type I interferon-beta expression during implant-related infections in co-culture and mouse model10.3389/fbioe.2023.1227148 ↗
58. fastp: an ultra-fast all-in-one FASTQ preprocessor10.1093/bioinformatics/bty560 ↗
59. MultiQC: summarize analysis results for multiple tools and samples in a single report10.1093/bioinformatics/btw354 ↗
60. Prokka: rapid prokaryotic genome annotation10.1093/bioinformatics/btu153 ↗
61. H. Li, Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM, arXiv preprint arXiv:1303.3997 (2013).
62. Twelve years of SAMtools and BCFtools10.1093/gigascience/giab008 ↗
63. HTSlib: C library for reading/writing high-throughput sequencing data10.1093/gigascience/giab007 ↗
64. FADU: a Quantification Tool for Prokaryotic Transcriptomic Analyses10.1128/mSystems.00917-20 ↗
65. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq210.1186/s13059-014-0550-8 ↗
66. Bacterial-Specific Induction of Inflammatory Cytokines Significantly Decreases upon Dual Species Infections of Implant Materials with Periodontal Pathogens in a Mouse Model10.3390/biomedicines10020286 ↗
67. Effect of titanium implants along with silver ions and tetracycline on type I interferon-beta expression during implant-related infections in co-culture and mouse model10.3389/fbioe.2023.1227148 ↗
68. Gene expression of Porphyromonas gingivalis ATCC 33277 when growing in an in vitro multispecies biofilm10.1371/journal.pone.0221234 ↗
69. Morphologic, phenotypic, and transcriptomic characterization of classically and alternatively activated canine blood-derived macrophages in vitro10.1371/journal.pone.0183572 ↗
70. Classically and alternatively activated bone marrow derived macrophages differ in cytoskeletal functions and migration towards specific CNS cell types10.1186/1742-2094-8-58 ↗
71. Gut microbiota induce IGF-1 and promote bone formation and growth10.1073/pnas.1607235113 ↗
72. Oncostatin M, an Inflammatory Cytokine Produced by Macrophages, Supports Intramembranous Bone Healing in a Mouse Model of Tibia Injury10.1016/j.ajpath.2014.11.008 ↗
73. Regulation of alkaline phosphatase and alpha 2(I) procollagen synthesis during early intramembranous bone formation in the rat mandible10.1111/j.1432-0436.1990.tb00619.x ↗
74. Antibiotic resistance in human peri-implantitis microbiota10.1111/clr.12160 ↗
75. Biomaterial and antibiotic strategies for peri-implantitis: A review10.1002/jbm.b.31152 ↗
76. Commensal and pathogenic biofilms differently modulate peri-implant oral mucosa in an organotypic model10.1111/cmi.13078 ↗
77. Identification of early microbial colonizers in human dental biofilm10.1111/j.1365-2672.2004.02420.x ↗
78. Calcium phosphate-based materials regulate osteoclast-mediated osseointegration10.1016/j.bioactmat.2021.05.003 ↗
79. Improving hydroxyapatite coating ability on biodegradable metal through laser-induced hydrothermal coating in liquid precursor: Application in orthopedic implants10.1016/j.bioactmat.2022.06.020 ↗
80. Influence of Surface Roughness, Nanostructure, and Wetting on Bacterial Adhesion10.1021/acs.langmuir.3c00091 ↗
81. Oral polymicrobial communities: Assembly, function, and impact on diseases10.1016/j.chom.2023.02.009 ↗
82. Antibiotics promote inflammation through the translocation of native commensal colonic bacteria10.1136/gutjnl-2014-309059 ↗
83. The salivary pellicle on dental biomaterials10.1016/j.colsurfb.2021.111570 ↗
84. Salivary pellicle modulates biofilm formation on titanium surfaces10.1007/s00784-023-05230-9 ↗
85. Lipopolysaccharide (Endotoxin)-host defense antibacterial peptides interactions: Role in bacterial resistance and prevention of sepsis10.1016/j.bbamem.2006.05.017 ↗
86. Antibiotic-induced Porphyromonas gingivalis LPS release and inhibition of LPS-stimulated cytokines by antimicrobial peptides10.1016/j.peptides.2010.06.001 ↗
87. Wound healing, fibroblast heterogeneity, and fibrosis10.1016/j.stem.2022.07.006 ↗
88. Image based Machine Learning for identification of macrophage subsets10.1038/s41598-017-03780-z ↗
89. Functions of ROS in Macrophages and Antimicrobial Immunity10.3390/antiox10020313 ↗
90. Macrophages overexpressing tartrate-resistant acid phosphatase show altered profile of free radical production and enhanced capacity of bacterial killing10.1016/j.bbrc.2005.03.133 ↗
91. Tartrate-resistant acid phosphatase facilitates hydroxyl radical formation and colocalizes with phagocytosed Staphylococcus aureus in alveolar macrophages10.1006/bbrc.2001.5715 ↗
92. Macrophage fate: to kill or not to kill?10.1128/iai.00476-23 ↗
93. Macrophages in Tissue Repair, Regeneration, and Fibrosis10.1016/j.immuni.2016.02.015 ↗
94. Macrophage-derived oncostatin M/bone morphogenetic protein 6 in response to Mg-based materials influences pro-osteogenic activity of human umbilical cord perivascular cells10.1016/j.actbio.2020.12.016 ↗
95. Induction of Osteogenesis in Mesenchymal Stem Cells by Activated Monocytes/Macrophages Depends on Oncostatin M Signaling10.1002/stem.1040 ↗
96. Oncostatin M regulates macrophages polarization in osseointegration via yes-associated protein10.1016/j.intimp.2023.110348 ↗
97. Bone regeneration is mediated by macrophage extracellular vesicles10.1016/j.bone.2020.115627 ↗
98. Macrophage Polarization and Osteoporosis: A Review10.3390/nu12102999 ↗
99. Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis10.1038/s41421-024-00689-6 ↗
100. The Bone Extracellular Matrix in Bone Formation and Regeneration