Doxycycline-integrated Silk Fibroin Hydrogel: Preparation, Characterizations, and Antimicrobial Assessment for Biomedical Applications

Overview

Journal BMC Oral Health

Publisher Biomed Central

Date 2025 Feb 1

PMID 39893416

Authors

Kranti Kiran Reddy Ealla

Chandra Sri Durga

Vikas Sahu

Neema Kumari

Jayachandran Venkatesan

Vishnu Priya Veeraraghavan

Pratibha Ramani

Kiran Kumar Bokara

Karthikeyan Ramalingam

Affiliations

Soon will be listed here.

Abstract

Background: Tooth extraction, a common dental procedure, is often accompanied by pain, trismus, and swelling due to alveolitis caused by oral bacteria. Doxycycline is prescribed to alleviate infection and improve socket healing, but its immediate absorption in the bloodstream makes the treatment less effective at oral sites. This emphasizes the importance of a drug delivery system to gradually slow its release at the oral wound site and increase its bioavailability to make the treatment effective over time.

Methods: Silk fibroin (SF) - doxycycline hyclate (DH) hydrogel was developed and subsequently characterized for gelation kinetics, swelling, stress-strain analysis, morphology using scanning electron microscopy, interaction between SF and DH using Fourier transform infrared (FT-IR) spectroscopy, drug release profile, antibacterial efficacy, and biocompatibility studies.

Results: The results indicated that the SF-DH hydrogel maintained its structural integrity, tolerated stress and strain, and featured interconnected pores, confirming DH integration within the SF matrix. The SF-DH hydrogel formed within 8 h with the pore size range of 20-150 μm and 90.72 kPa Young's modulus. The drug release profile showed the increased release of DH up to 2 h, followed by sustained release till 8 h. The zone of inhibition was smaller with SF-DH hydrogels compared with DH for both Staphylococcus aureus and Streptococcus mutans. Furthermore, MC3T3-E1 cells showed 90% viability with SF-DH hydrogel.

Conclusions: The findings suggest that SF-DH hydrogel showed sufficient mechanical strength, pore size, antimicrobial activity, and biocompatibility. Further in vivo and clinical tests are required to prove its efficacy in effective socket healing.

References

Ghalei S, Handa H . A Review on Antibacterial Silk Fibroin-based Biomaterials: Current State and Prospects. Mater Today Chem. 2021; 23. PMC: 8664245. DOI: 10.1016/j.mtchem.2021.100673. View

Tavakoli M, Al-Musawi M, Kalali A, Shekarchizadeh A, Kaviani Y, Mansouri A . Platelet rich fibrin and simvastatin-loaded pectin-based 3D printed-electrospun bilayer scaffold for skin tissue regeneration. Int J Biol Macromol. 2024; 265(Pt 1):130954. DOI: 10.1016/j.ijbiomac.2024.130954. View

Kumari N, Pullaguri N, Sahu V, Ealla K . Research and therapeutic applications of silk proteins in cancer. J Biomater Appl. 2023; 38(1):39-50. DOI: 10.1177/08853282231184572. View

Chen B, Kankala R, Chen A, Yang D, Cheng X, Jiang N . Investigation of silk fibroin nanoparticle-decorated poly(l-lactic acid) composite scaffolds for osteoblast growth and differentiation. Int J Nanomedicine. 2017; 12:1877-1890. PMC: 5352233. DOI: 10.2147/IJN.S129526. View

Henehan M, Montuno M, De Benedetto A . Doxycycline as an anti-inflammatory agent: updates in dermatology. J Eur Acad Dermatol Venereol. 2017; 31(11):1800-1808. DOI: 10.1111/jdv.14345. View

Toledano-Osorio M, De Luna-Bertos E, Toledano M, Manzano-Moreno F, Garcia-Recio E, Ruiz C . Doxycycline-doped collagen membranes accelerate in vitro osteoblast proliferation and differentiation. J Periodontal Res. 2022; 58(2):296-307. DOI: 10.1111/jre.13091. View

Varghese J, Chellappa N, Fathima N . Gelatin-carrageenan hydrogels: role of pore size distribution on drug delivery process. Colloids Surf B Biointerfaces. 2013; 113:346-51. DOI: 10.1016/j.colsurfb.2013.08.049. View

Bystedt H, Nord C, NORDENRAM A . Effect of azidocillin, erythromycin, clindamycin and doxycycline on postoperative complications after surgical removal of impacted mandibular third molars. Int J Oral Surg. 1980; 9(3):157-65. DOI: 10.1016/s0300-9785(80)80014-7. View

Montalban M, Coburn J, Lozano-Perez A, Cenis J, Villora G, Kaplan D . Production of Curcumin-Loaded Silk Fibroin Nanoparticles for Cancer Therapy. Nanomaterials (Basel). 2018; 8(2). PMC: 5853757. DOI: 10.3390/nano8020126. View

10.

Sun W, Gregory D, Anas Tomeh M, Zhao X . Silk Fibroin as a Functional Biomaterial for Tissue Engineering. Int J Mol Sci. 2021; 22(3). PMC: 7867316. DOI: 10.3390/ijms22031499. View

11.

Khaing E, Lertsuphotvanit N, Thammasut W, Rojviriya C, Chansatidkosol S, Phattarateera S . Cellulose Acetate Butyrate-Based In Situ Gel Comprising Doxycycline Hyclate and Metronidazole. Polymers (Basel). 2025; 16(24. PMC: 11728690. DOI: 10.3390/polym16243477. View

12.

Udeabor S, Heselich A, Al-Maawi S, Alqahtani A, Sader R, Ghanaati S . Current Knowledge on the Healing of the Extraction Socket: A Narrative Review. Bioengineering (Basel). 2023; 10(10). PMC: 10604628. DOI: 10.3390/bioengineering10101145. View

13.

Mottaghitalab F, Kiani M, Farokhi M, Kundu S, Reis R, Gholami M . Targeted Delivery System Based on Gemcitabine-Loaded Silk Fibroin Nanoparticles for Lung Cancer Therapy. ACS Appl Mater Interfaces. 2017; 9(37):31600-31611. DOI: 10.1021/acsami.7b10408. View

14.

Seib F, Jones G, Rnjak-Kovacina J, Lin Y, Kaplan D . pH-dependent anticancer drug release from silk nanoparticles. Adv Healthc Mater. 2013; 2(12):1606-11. PMC: 3808531. DOI: 10.1002/adhm.201300034. View

15.

Kanwal A, Iqbal A, Arshad R, Akhtar S, Razzaq S, Ahmad N . Formulation and Evaluation of Novel Thiolated Intra Pocket Periodontal Composite Membrane of Doxycycline. AAPS PharmSciTech. 2019; 20(8):325. DOI: 10.1208/s12249-019-1536-3. View

16.

Chuysinuan P, Nooeaid P, Thanyacharoen T, Techasakul S, Pavasant P, Kanjanamekanant K . Injectable eggshell-derived hydroxyapatite-incorporated fibroin-alginate composite hydrogel for bone tissue engineering. Int J Biol Macromol. 2021; 193(Pt A):799-808. DOI: 10.1016/j.ijbiomac.2021.10.132. View

17.

Lertsuphotvanit N, Tuntarawongsa S, Chantadee T, Phaechamud T . Phase Inversion-Based Doxycycline Hyclate-Incorporated Borneol In Situ Gel for Periodontitis Treatment. Gels. 2023; 9(7). PMC: 10380060. DOI: 10.3390/gels9070557. View

18.

Sordi M, Curtarelli R, da Silva I, Fongaro G, Benfatti C, Magini R . Effect of dexamethasone as osteogenic supplementation in in vitro osteogenic differentiation of stem cells from human exfoliated deciduous teeth. J Mater Sci Mater Med. 2021; 32(1):1. PMC: 7815568. DOI: 10.1007/s10856-020-06475-6. View

18.

Kazemi N, Javad Mahalati M, Kaviani Y, Al-Musawi M, Varshosaz J, Bakhtiari S . Core-shell nanofibers containing L-arginine stimulates angiogenesis and full thickness dermal wound repair. Int J Pharm. 2024; 653:123931. DOI: 10.1016/j.ijpharm.2024.123931. View

19.

Hu J, Jiang Z, Zhang J, Yang G . Application of silk fibroin coatings for biomaterial surface modification: a silk road for biomedicine. J Zhejiang Univ Sci B. 2023; 24(11):943-956. PMC: 10646393. DOI: 10.1631/jzus.B2300003. View