Abstract Objectives Titanium platelet–rich fibrin (T-PRF), a second-generation autogenous blood concentrate with tough and thick fibrin meshwork activated by a titanium tube, was used as a drug carrier for doxycycline (Doxy) by injection. The objective of this study is to evaluate the loading capacity of T-PRF, release kinetics of doxycycline-loaded T-PRF, and its antibacterial effects against S. aureus and P. aeruginosa. Materials and methods The T-PRF and collagen were loaded with Doxy as T-PRF/Doxy and Collagen/Doxy, and their release and antibacterial activities against S. aureus and P. aeruginosa were investigated. Chemical characterization and morphological analysis were performed. Results In comparison with collagen, approximately sevenfold more Doxy, 281 mg/g, was loaded into TPRF. It was found that 25% of the loaded Doxy was released from T-PRF compared to only 12% from collagen within 72 h. The largest inhibition zone diameter (IZD) was observed for TPRF/Dox with 32 ± 6 mm and 37 ± 5 mm for P. aereginosa and S. aureus, respectively. However, only 10 ± 5 mm and 10 ± 6 mm IZD were observed for bare T-PRF, and no inhibition zone was observed for the Collagen/Doxy group. A dense fibrin structure was visualized on SEM images of the T-PRF/Doxy group compared to the T-PRF group. Conclusions T-PRF has higher Doxy loading capacity and long-acting antibacterial effects compared to collagen. T-PRF was shown to have potential autogenous long-term drug-carrying capability for doxycycline. Also, the potential fibrinophilic properties of Doxy were observed to strengthen the structure of T-PRF. Clinical relevance T-PRF is an autogenous drug career with high loading capacity and extended antibacterial effects for doxycycline. Doxycycline molecules can be visible on T-PRF fibers. This study suggests that T-PRF/Dox could be used as a proper antibiotic delivery device in the treatments of periodontitis and peri-implantitis. This is a preview of subscription content, access via your institution. References 1. Joseph S (2000) Curtis MA (2021) Microbial transitions from health to disease. Periodontol 86:201–209. https://doi.org/10.1111/prd.12377 Article Google Scholar 2. Hajishengallis G (2000) Lamont RJ (2021) Polymicrobial communities in periodontal disease: Their quasi-organismal nature and dialogue with the host. Periodontol 86:210–230. https://doi.org/10.1111/prd.12371 Article Google Scholar 3. Sedghi L, DiMassa V, Harrington A et al (2000) (2021) The oral microbiome: role of key organisms and complex networks in oral health and disease. Periodontol 87:107–131. https://doi.org/10.1111/prd.12393 Article Google Scholar 4. Lamont RJ, Koo H, Hajishengallis G (2018) The oral microbiota: dynamic communities and host interactions 5. Beck JD, Papapanou PN, Philips KH, Offenbacher S (2019) Periodontal medicine: 100 years of progress. J Dent Res 98:1053– 1062. https://doi.org/10.1177/0022034519846113 Article PubMed Google Scholar 6. Szulc M, Zakrzewska A, Zborowski J (2018) Local drug delivery in periodontitis treatment: a review of contemporary literature. Dent Med Probl 55:333–342. https://doi.org/10.17219/DMP/94890 7. Arweiler NB, Pietruska M, Pietruski J et al (2014) Six-month results following treatment of aggressive periodontitis with antimicrobial photodynamic therapy or amoxicillin and metronidazole. Clin Oral Investig 18:2129–2135. https://doi.org/10.1007/s00784-014-1193-6 Article PubMed Google Scholar 8. Cosgarea R, Eick S, Batori-Andronescu I et al (2021) Clinical and microbiological evaluation of local doxycycline and antimicrobial photodynamic therapy during supportive periodontal therapy: a randomized clinical trial. Antibiotics 10:1– 12. https://doi.org/10.3390/antibiotics10030277 Article Google Scholar 9. Jepsen K (2000) Jepsen S (2016) Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis. Periodontol 71:82–112. https://doi.org/10.1111/prd.12121 Article Google Scholar 10.Hanes PJ, Purvis JP (2003) Local anti-infective therapy: pharmacological agents A systematic review. Ann Periodontol 8:79– 98. https://doi.org/10.1902/annals.2003.8.1.79 Article PubMed Google Scholar 11. Joshi D, Garg T, Goyal AK, Rath G (2016) Advanced drug delivery approaches against periodontitis. Drug Deliv 23:363– 377. https://doi.org/10.3109/10717544.2014.935531 Article PubMed Google Scholar 12. H.R. R, Dhamecha D, Jagwani S, et al (2019) Local drug delivery systems in the management of periodontitis: a scientific review. J Control Release 307:393– 409. https://doi.org/10.1016/j.jconrel.2019.06.038 Article Google Scholar 13. Steinberg D (2000) Friedman M (2020) Sustained-release delivery of antimicrobial drugs for the treatment of periodontal diseases: fantasy or already reality? Periodontol 84:176– 187. https://doi.org/10.1111/prd.12341 Article Google Scholar 14. Newman, Michael G., Take, i Henry H., Klokkevold, Perry R., Carranza FA (2017) Newman and Carranza’s clinical periodontology thirteenth edition. J Chem Inf Model 53:1689–1699 15. Ahamed S, Jalaluddin M, Khalid I et al (2013) The use of controlled release locally delivered 10% doxycycline hyclate gel as an adjunct to scaling and root planing in the treatment of chronic periodontitis: clinical and microbiological results. J Contemp Dent Pr 14:1080– 1086. https://doi.org/10.5005/jp-journals-10024-1455 Article Google Scholar 16. Deo V, Ansari S, Mandia S, Bhongade M (2010) Therapeutic efficacy of subgingivally delivered doxycycline hyclate as an adjunct to non-surgical treatment of chronic periodontitis. J Oral Maxillofac Res 2:1– 7. https://doi.org/10.5037/jomr.2011.2103 Article Google Scholar 17. Vega-Vásquez P, Mosier NS, Irudayaraj J (2020) Nanoscale drug delivery systems: from medicine to agriculture. Front Bioeng Biotechnol 8:1–16. https://doi.org/10.3389/fbioe.2020.00079 Article Google Scholar 18. Tihan GT, Rău I, Zgârian RG et al (2019) Oxytetracycline versus doxycycline collagen sponges designed as potential carrier supports in biomedical applications. Pharmaceutics 11:1– 21. https://doi.org/10.3390/pharmaceutics11080363 Article Google Scholar 19. Mishra M, Mishra B (2012) Mucoadhesive microparticles as potential carriers in inhalation delivery of doxycycline hyclate: a comparative study. Acta Pharm Sin B 2:518– 526. https://doi.org/10.1016/j.apsb.2012.05.001 Article Google Scholar 20. Dohan DM, Choukroun J, Diss A, et al (2006) Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features. Oral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology 101: https://doi.org/10.1016/j.tripleo.2005.07.009 21. Castro AB, Herrero ER, Slomka V et al (2019) Antimicrobial capacity of leucocyte-and platelet rich fibrin against periodontal pathogens. Sci Rep 9:1–8. https://doi.org/10.1038/s41598-019-44755-6 Article Google Scholar 22. Egle K, Salma I, Dubnika A (2021) From blood to regenerative tissue : how autologous platelet-rich fibrin can be combined with other materials to ensure controlled drug and growth factor release. Int J Mol Sci 22 23. Miron RJ, Moraschini V, Fujioka-Kobayashi M et al (2021) Use of platelet-rich fibrin for the treatment of periodontal intrabony defects: a systematic review and meta-analysis. Clin Oral Investig 25:2461– 2478. https://doi.org/10.1007/s00784-021-03825-8 Article PubMed PubMed Central Google Scholar 24. Tunali M, Özdemir H, Küçükodaci Z, et al (2014) A novel platelet concentrate: titanium-prepared platelet-rich fibrin. Biomed Res Int 2014: https://doi.org/10.1155/2014/209548 25. Miron R, Choukroun J, Ghanaati S (2022) Controversies related to scientific report describing G - forces from studies on platelet-rich fibrin: necessity for standardization of relative centrifugal force values. https://doi.org/10.4103/GFSC.GFSC 26. Miron RJ, Pinto NR, Quirynen M, Ghanaati S (2019) Standardization of relative centrifugal forces in studies related to platelet-rich fibrin. J Periodontol 90:817– 820. https://doi.org/10.1002/JPER.18-0553 Article PubMed Google Scholar 27.Ustaoğlu G, Ercan E, Tunali M (2016) The role of titanium-prepared platelet-rich fibrin in palatal mucosal wound healing and histoconduction. Acta Odontol Scand 74:558– 564. https://doi.org/10.1080/00016357.2016.1219045 Article PubMed Google Scholar 28. Sahiner N, Suner SS, Kurt SB et al (2021) HA particles as resourceful cancer, steroidal and antibiotic drug delivery device with sustainable and multiple drug release capability. J Macromol Sci Part A Pure Appl Chem 58:145– 155. https://doi.org/10.1080/10601325.2020.1832518 Article Google Scholar 29. Suner SS, Sahiner M, Ayyala RS et al (2021) Versatile fluorescent carbon dots from citric acid and cysteine with antimicrobial, anti- biofilm, antioxidant, and AChE enzyme inhibition capabilities. J Fluoresc 31:1705–1717. https://doi.org/10.1007/s10895-021-02798-x Article PubMed Google Scholar 30. Lambs L, Brion M, Berthon G (1984) Metal ion-tetracycline interactions in biological fluids. Part 3. Formation of mixed-metal ternary complexes of tetracycline, oxytetracycline, doxycycline and minocycline with calcium and magnesium, and their involvement in the bioavailability of these an. Agents Actions 14:743– 750. https://doi.org/10.1007/BF01978919 Article PubMed Google Scholar 31. Khader H, Solodushko V, Al-Mehdi AB et al (2014) Overlap of doxycycline fluorescence with that of the redox-sensitive intracellular reporter roGFP. J Fluoresc 24:305– 311. https://doi.org/10.1007/s10895-013-1331-6 Article PubMed Google Scholar 32. Stoller NH, Johnson LR, Trapnell S et al (1998) The pharmacokinetic profile of a biodegradable controlled-release delivery system containing doxycycline compared to systemically delivered doxycycline in gingival crevicular fluid, saliva, and serum. J Periodontol 69:1085–1091. https://doi.org/10.1902/jop.1998.69.10.1085 Article PubMed Google Scholar 33. Moura LA, Ribeiro FV, Aiello TB et al (2015) Characterization of the release profile of doxycycline by PLGA microspheres adjunct to nonsurgical periodontal therapy. J Biomater Sci Polym Ed 26:573– 584. https://doi.org/10.1080/09205063.2015.1045249 Article PubMed Google Scholar 34. Cai Z, Li Y, Wang Y et al (2019) Antimicrobial effects of photodynamic therapy with antiseptics on Staphylococcus aureus biofilm on titanium surface. Photodiagnosis Photodyn Ther 25:382– 388. https://doi.org/10.1016/j.pdpdt.2019.01.024 Article PubMed Google Scholar 35. Souto R, Silva-Boghossian CM, Colombo APV (2014) Prevalence of Pseudomonas aeruginosa and Acinetobacter spp. in subgingival biofilm and saliva of subjects with chronic periodontal infection. Brazilian J Microbiol 45:495–501. https://doi.org/10.1590/S151783822014000200017 Article Google Scholar 36. Feng M, Wang Y, Zhang P et al (2020) Antibacterial effects of platelet-rich fibrin produced by horizontal centrifugation. Int J Oral Sci 12:1–8. https://doi.org/10.1038/s41368-020-00099-w Article Google Scholar 37.Burnouf T, Chou ML, Wu YW et al (2013) Antimicrobial activity of platelet (PLT)-poor plasma, PLT-rich plasma, PLT gel, and solvent/detergent-treated PLT lysate biomaterials against wound bacteria. Transfusion 53:138–146. https://doi.org/10.1111/j.15372995.2012.03668.x Article PubMed Google Scholar 38. Bielecki TM, Gazdzik TS, Arendt J et al (2007) Antibacterial effect of autologous platelet gel enriched with growth factors and other active substances: an in vitro study. J Bone Jt Surg - Ser B 89:417– 420. https://doi.org/10.1302/0301-620X.89B3.18491 Article Google Scholar 39. Miron RJ, Zhang Y (2018) Autologous liquid platelet rich fibrin: a novel drug delivery system. Acta Biomater 75:35– 51. https://doi.org/10.1016/j.actbio.2018.05.021 Article PubMed Google Scholar 40. Polak D, Clemer-Shamai N, Shapira L (2019) Incorporating antibiotics into platelet-rich fibrin: a novel antibiotics slow-release biological device. J Clin Periodontol 46:241– 247. https://doi.org/10.1111/jcpe.13063 Article PubMed Google Scholar 41. Pillai AK, Thomas S, Seth S, et al (2021) Platelet rich fibrin (PRF) gel as efficient vehicle for local drug delivery in minor oral surgical defects. 185–191 42. Donmezer CM, Bilginaylar K (2021) Comparison of the postoperative effects of local antibiotic versus systemic antibiotic with the use of platelet-rich fibrin on impacted mandibular third molar surgery: a randomized split-mouth study. Biomed Res Int 2021:1– 7. https://doi.org/10.1155/2021/3040661 Article Google Scholar 43. Xing R, Witso IL, Jugowiec D, et al (2015) Antibacterial effect of doxycycline-coated dental abutment surfaces. Biomed Mater 10: https://doi.org/10.1088/1748-6041/10/5/055003 Download references Acknowledgements The authors are also grateful to Dr. Süleyman Sami Doğangün and the volunteer pre-graduate students of Canakkale Onsekiz Mart University Faculty of Dentistry for their valuable contribution to performing the study. Funding The authors thank Canakkale Onsekiz Mart University Scientific Research Council. This Project was supported by COMU-BAP with Project number TSA-2021–3494. Author information Authors and Affiliations 1. Department of Periodontology, Faculty of Dentistry, Canakkale Onsekiz Mart University, 17110, Canakkale, Turkey Esra Ercan & Mustafa Tunali 2. Department of Chemistry, Faculty of Sciences & Arts, and Nanoscience and Technology Research and Application Center (NANORAC), Canakkale Onsekiz Mart University, Terzioglu Campus, Canakkale, 17100, Turkey Selin S. Suner, Selehattin Yilmaz & Nurettin Sahiner 3. Department of Pharmacology, Faculty of Medicine, Canakkale Onsekiz Mart University, Terzioglu Campus, Canakkale, 17100, Turkey Coskun Silan 4. Department of Biostatistics, Faculty of Medicine, Canakkale Onsekiz Mart University, Terzioglu Campus, 17100, Canakkale, Turkey Duygu Siddikoglu 5. Department of Ophthalmology, Morsani College of Medicine, University of South Florida, Tampa, FL, 33620, USA Nurettin Sahiner 6. Department of Chemical & Biomedical Engineering, and Materials Science and Engineering Program, University of South Florida, Tampa, FL, 33620, USA Nurettin Sahiner Corresponding author Correspondence to Esra Ercan. Ethics declarations Ethics approval and consent to participate Approval was obtained from Çanakkale Onsekiz Mart University Clinical Research Ethics Committee (number: 2020/13; date: November 11, 2020) at the beginning of this study. The written informed consent was obtained from study participants. Conflict of interest The authors declare no competing interests. Additional information Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Supplementary file1 (DOCX 128 KB) Rights and permissions