Keratin hydrogels support the sustained release of bioactive ciprofloxacin
Abstract
Keratins are naturally derived proteins that can be fabricated into several biomaterial forms including hydrogels. These materials are a potential polymeric system for several tissue engineering and regenerative medicine applications due to their ability to support cell attachment, proliferation, and migration. However, little is known regarding their ability to support sustained release of therapeutic agents. This report describes the use of keratin hydrogels for sustained release of the antibiotic ciprofloxacin, which may prove useful to traumatic injury applications that would benefit from materials promoting tissue regeneration while also preventing acute infection. Hydrogels were formed from keratins obtained by oxidative extraction and known as keratose. We found that keratose hydrogels released ∼60% of loaded ciprofloxacin over the first 10 days and that continued release was detectable over the course of 3 weeks. Released ciprofloxacin was bioactive, inhibiting growth of Staphylococcus aureus for 23 days in vitro and for 2 weeks in a mouse subcutaneous model. The rate of ciprofloxacin release was highly correlated with degradation of the keratin hydrogel and not consistent with simple diffusion. Further experiments indicated that ciprofloxacin binds to keratose through electrostatic interactions. These studies demonstrate the specific use of keratose hydrogels for the release of antibiotic and the potential for the more general use of this material in tissue engineering and regenerative medicine applications. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
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Cites
The pharmacological basis of therapeutics
Frank, A. L. (1981) · Environmental Research · doi:10.1016/0013-9351(81)90176-6 · Cited by 2,738 · see citing works
The human keratins: biology and pathology
Moll, R., Divo, M., & Langbein, L. (2008) · Histochemistry and Cell Biology · doi:10.1007/s00418-008-0435-6 · Cited by 1,465 · see citing works
Kim, K., Luu, Y. K., Chang, C., Fang, D., Hsiao, B. S., Chu, B., & Hadjiargyrou, M. (2004) · Journal of Controlled Release · doi:10.1016/j.jconrel.2004.04.009 · Cited by 756 · see citing works
New consensus nomenclature for mammalian keratins
Schweizer, J., Bowden, P. E., Coulombe, P. A., Langbein, L., Lane, E. B., Magin, T. M., Maltais, L. J., Omary, M. B., Parry, D. A. D., Rogers, M. A., et al. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200603161 · Cited by 740 · see citing works
A Review of Keratin-Based Biomaterials for Biomedical Applications
Rouse, J. G., & Dyke, M. E. V. (2010) · Materials · doi:10.3390/ma3020999 · Cited by 662 · see citing works
Self-citationAntibiotic-eluting medical devices for various applications
ZILBERMAN, M., & ELSNER, J. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.05.020 · Cited by 610 · see citing works
Biochemical features of microbial keratinases and their production and applications
Brandelli, A., Daroit, D. J., & Riffel, A. (2009) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-009-2398-5 · Cited by 450 · see citing works
Some properties of keratin biomaterials: Kerateines
Hill, P., Brantley, H., & Van Dyke, M. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2009.09.076 · Cited by 349 · see citing works
Self-citationHill, P. S., Garrett, J. P., Ma, J., Apel, P. J., Klorig, D. C., Smith, T. L., Koman, L. A., Atala, A., & Dyke, M. E. V. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.08.023 · Cited by 346 · see citing works
Self-citationLocal Antibiotic Therapy in the Treatment of Open Fractures and Osteomyelitis
Zalavras, C. G., Patzakis, M. J., & Holtom, P. D. (2004) · Clinical Orthopaedics and Related Research · doi:10.1097/01.blo.0000143571.18892.8d · Cited by 329 · see citing works
Crewther, W. G., Fraser, R., Lennox, F. G., & Lindley, H. (1965) · Advances in protein chemistry · doi:10.1016/s0065-3233(08)60390-3 · Cited by 306 · see citing works
Fabrication of wool keratin sponge scaffolds for long-term cell cultivation
Tachibana, A., Furuta, Y., Takeshima, H., Tanabe, T., & Yamauchi, K. (2002) · Journal of Biotechnology · doi:10.1016/s0168-1656(01)00395-9 · Cited by 301 · see citing works
Polymethylmethacrylate: Properties and Contemporary Uses in Orthopaedics
Jaeblon, T. (2010) · Journal of the American Academy of Orthopaedic Surgeons · doi:10.5435/00124635-201005000-00006 · Cited by 228 · see citing works
Films based on human hair keratin as substrates for cell culture and tissue engineering
Reichl, S. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.08.051 · Cited by 217 · see citing works
Li, B., Brown, K. V., Wenke, J. C., & Guelcher, S. A. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.04.002 · Cited by 198 · see citing works
Novel approach to fabricate keratin sponge scaffolds with controlled pore size and porosity
Katoh, K., Tanabe, T., & Yamauchi, K. (2003) · Biomaterials · doi:10.1016/j.biomaterials.2003.11.018 · Cited by 193 · see citing works
Kaye, K. S., Engemann, J. J., Fraimow, H. S., & Abrutyn, E. (2004) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2004.04.003 · Cited by 181 · see citing works
Preparation of scaffolds from human hair proteins for tissue-engineering applications
Verma, V., Verma, P., Ray, P., & Ray, A. R. (2008) · Biomedical Materials · doi:10.1088/1748-6041/3/2/025007 · Cited by 180 · see citing works
Cultivation of fibroblast cells on keratin-coated substrata
Yamauchi, K., Maniwa, M., & Mori, T. (1998) · Journal of Biomaterials Science Polymer Edition · doi:10.1163/156856298x00640 · Cited by 158 · see citing works
Aboushwareb, T. A., Eberli, D., Ward, C., Broda, C., Holcomb, J. B., Atala, A., & Dyke, M. E. V. (2008) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.31251 · Cited by 147 · see citing works
Self-citationSystemic Antimicrobial Therapy in Osteomyelitis
Fraimow, H. S. (2009) · Seminars in Plastic Surgery · doi:10.1055/s-0029-1214161 · Cited by 141 · see citing works
Novel antibacterial nanofibrous PLLA scaffolds
Feng, K. M., Sun, H., Bradley, M. A., Dupler, E. J., Giannobile, W. V., & Ma, P. X. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.05.035 · Cited by 141 · see citing works
Preparation and physicochemical properties of compression-molded keratin films
Katoh, K., Shibayama, M., Tanabe, T., & Yamauchi, K. (2003) · Biomaterials · doi:10.1016/j.biomaterials.2003.09.021 · Cited by 139 · see citing works
Shi, M. Q., Kretlow, J. D., Nguyen, A., Young, S. W., Baggett, L. S., Wong, M. E., Kasper, F. K., & Mikos, A. G. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.01.112 · Cited by 114 · see citing works
Gentamicin extended release from an injectable polymeric implant
Krasko, M. Y., Golenser, J., Nyska, A., Nyska, M., Brin, Y. S., & Domb, A. J. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.10.010 · Cited by 114 · see citing works
Toward a common language: surgical wound bed preparation and debridement
Granick, M. S., Boykin, J. V., Gamelli, R. L., Schultz, G. S., & Tenenhaus, M. (2006) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2005.00096.x · Cited by 113 · see citing works
The expanding role of fluoroquinolones
Schaeffer, A. J. (2002) · The American Journal of Medicine · doi:10.1016/s0002-9343(02)01059-8 · Cited by 107 · see citing works
Delivery of rapamycin to dendritic cells using degradable microparticles
Jhunjhunwala, S., Raimondi, G., Thomson, A. W., & Little, S. R. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.10.011 · Cited by 96 · see citing works
Modified keratin sponge: Binding of bone morphogenetic protein-2 and osteoblast differentiation
Tachibana, A., Nishikawa, Y., Nishino, M., Kaneko, S., Tanabe, T., & Yamauchi, K. (2006) · Journal of Bioscience and Bioengineering · doi:10.1263/jbb.102.425 · Cited by 94 · see citing works
Effective Treatment of Osteomyelitis with Biodegradable Microspheres in a Rabbit Model
Ambrose, C. G., Clyburn, T. A., Louden, K., Joseph, J., Wright, J., Gulati, P., Gogola, G. R., & Mikos, A. G. (2004) · Clinical Orthopaedics and Related Research · doi:10.1097/01.blo.0000126303.41711.a2 · Cited by 85 · see citing works
Sando, L., Kim, M., Colgrave, M. L., Ramshaw, J. A. M., Werkmeister, J. A., & Elvin, C. M. (2010) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32913 · Cited by 78 · see citing works
Effectiveness of commercially-available antibiotic-impregnated implants
Wenke, J. C., Owens, B. D., Svoboda, S. J., & Brooks, D. E. (2006) · Journal of Bone and Joint Surgery - British Volume · doi:10.1302/0301-620x.88b8.17368 · Cited by 57 · see citing works
Ikkai, F., & Naito, S. (2002) · Biomacromolecules · doi:10.1021/bm010160i · Cited by 51 · see citing works
Collagen bilayer dressing with ciprofloxacin, an effective system for infected wound healing
Sripriya, R., Muthusamy, S., Ahmed, M. R., & Sehgal, P. K. (2007) · Journal of Biomaterials Science Polymer Edition · doi:10.1163/156856207779996913 · Cited by 49 · see citing works
Biocompatibility and osseointegration of reconstituted keratin in an ovine model
Dias, G. J., Peplow, P. V., McLaughlin, A. W., Teixeira, F. S., & Kelly, R. J. (2009) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32394 · Cited by 49 · see citing works
Segev, S., Yaniv, I., Haverstock, D. C., & Reinhart, H. H. (1999) · Clinical Infectious Diseases · doi:10.1086/515132 · Cited by 48 · see citing works
Granick, M. S., Tenenhaus, M., Knox, K. R., & Ulm, J. P. (2007) · PubMed · Cited by 43 · see citing works
Bernot, K. M., Lee, C., & Coulombe, P. A. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200408116 · Cited by 43 · see citing works
Characterization of ciprofloxacin binding to the linear single- and double-stranded DNA
Vilfan, I. D., Drevenšek, P., Turel, I., & Ulrih, N. P. (2003) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(03)00135-0 · Cited by 42 · see citing works
Ristiniemi, J. Y., Lakovaara, M., Flinkkilä, T. E., & Jalovaara, P. (2007) · Acta Orthopaedica · doi:10.1080/17453670710014176 · Cited by 38 · see citing works
Covalent coating of hydroxyapatite by keratin stabilizes gentamicin release
Belcarz, A., Ginalska, G., Zalewska, J., Rzeski, W., Slosarczyk, A., Kowalczuk, D., Godlewski, P., & Niedźwiadek, J. (2008) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.31192 · Cited by 36 · see citing works
Extracellular expression of keratinase Ker P from Pseudomonas aeruginosa in E. coli
Sharma, R., & Gupta, R. (2010) · Biotechnology Letters · doi:10.1007/s10529-010-0361-2 · Cited by 35 · see citing works
In vitro degradation of keratin by two species of Bacillus.
Lal, S., Rajak, R. C., & Hasija, S. K. (1999) · The Journal of General and Applied Microbiology · doi:10.2323/jgam.45.283 · Cited by 18 · see citing works
Klein, L. K., Yancey, R. J., Case, C., & Salmon, S. A. (1996) · Journal of Veterinary Diagnostic Investigation · doi:10.1177/104063879600800418 · Cited by 11 · see citing works
Prokuski, L. J. (2006) · Journal of the American Academy of Orthopaedic Surgeons · doi:10.5435/00124635-200600001-00024 · Cited by 11 · see citing works
Flagged first, then by citations
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Sorted by citations
Keratin: dissolution, extraction and biomedical application
Shavandi, A., Silva, T. H., Bekhit, A. A., & Bekhit, A. E.-D. A. (2017) · Biomaterials Science · doi:10.1039/c7bm00411g · Cited by 537 · see citing works
Keratin - Based materials for biomedical applications
Feroz, S., Muhammad, N., Ratnayake, J. T., & Dias, G. J. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.04.007 · Cited by 389 · see citing works
“The incorporation of Ciprofloxacin in a keratin hydrogel resulted in 60% of the drug release during 10 days [169].”
MethodRecent trends in protein and peptide-based biomaterials for advanced drug delivery
Varanko, A. K., Saha, S., & Chilkoti, A. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.08.008 · Cited by 371 · see citing works
“to locally deliver and sustain the release of ciprofloxacin, a broad-range antibiotic [114].”
Eslahi, N., Abdorahim, M., & Simchi, A. (2016) · Biomacromolecules · doi:10.1021/acs.biomac.6b01235 · Cited by 255 · see citing works
Borrowing From Nature: Biopolymers and Biocomposites as Smart Wound Care Materials
Suarato, G., Bertorelli, R., & Athanassiou, A. (2018) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2018.00137 · Cited by 196 · see citing works
Kowalczewski, C. J., & Saul, J. M. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00513 · Cited by 170 · see citing works
“, 2004) or injectable gel (Aboushwareb et al., 2009; Saul et al., 2011; Kowalczewski et al., 2014) which allows for minimally invasive administration able to contour to any defect shape.”
BackgroundSelf-citationHuman hair keratin and its-based biomaterials for biomedical applications
Lee, H., Noh, K., Lee, S. C., Kwon, I.-K., Han, D., Lee, I.-S., & Hwang, Y. (2014) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-014-0029-4 · Cited by 150 · see citing works
Bone regeneration with BMP-2 delivered from keratose scaffolds
de Guzman, R. C., Saul, J. M., Ellenburg, M. D., Merrill, M. R., Coan, H. B., Smith, T. L., & Van Dyke, M. E. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2012.11.002 · Cited by 147 · see citing works
Self-citationKeratinous materials: Structures and functions in biomedical applications
Rajabi, M., Ali, A., McConnell, M. A., & Cabral, J. D. (2020) · Materials Science and Engineering C · doi:10.1016/j.msec.2019.110612 · Cited by 134 · see citing works
Evaluation of keratin extraction from wool by chemical methods for bio-polymer application
Shavandi, A., Bekhit, A. E. A., Carne, A., & Bekhit, A. A. (2016) · Journal of Bioactive and Compatible Polymers · doi:10.1177/0883911516662069 · Cited by 118 · see citing works
The Use of Keratin in Biomedical Applications
Vasconcelos, A., & Cavaco-Paulo, A. M. (2013) · Current Drug Targets · doi:10.2174/1389450111314050010 · Cited by 117 · see citing works
Li, Y., Zhi, X., Lin, J., You, X., & Yuan, J. (2016) · Materials Science and Engineering C · doi:10.1016/j.msec.2016.12.067 · Cited by 116 · see citing works
“Van Dyke group have described the delivery and activity of the antibiotic ciprofloxacin delivered from keratin hydrogel[24].”
BackgroundValorization of keratin waste biomass and its potential applications
Chilakamarry, C. R., Khilji, I. A., Gupta, A. K., Bhuyar, P., Mahmood, S., AL-Japairai, K. A. S., & Chua, G. K. (2021) · Journal of Water Process Engineering · doi:10.1016/j.jwpe.2020.101707 · Cited by 114 · see citing works
Tunable Keratin Hydrogels for Controlled Erosion and Growth Factor Delivery
Ham, T. R., Lee, R. T., Han, S., Haque, S., Vodovotz, Y., Gu, J., Burnett, L. R., Tomblyn, S., & Saul, J. M. (2016) · Biomacromolecules · doi:10.1021/acs.biomac.5b01328 · Cited by 111 · see citing works
Self-citationIn vitro response of macrophage polarization to a keratin biomaterial
Fearing, B. V., & Dyke, M. E. V. (2014) · Acta Biomaterialia · doi:10.1016/j.actbio.2014.04.003 · Cited by 109 · see citing works
Self-citationKeratin films for ocular surface reconstruction: Evaluation of biocompatibility in an in-vivo model
Borrelli, M., Joepen, N., Reichl, S., Finis, D., Schoppe, M., Geerling, G., & Schrader, S. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.11.038 · Cited by 98 · see citing works
Keratin Hydrogel Enhances In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss
Passipieri, J. A., Baker, H. B., Siriwardane, M. L., Ellenburg, M. D., Vadhavkar, M., Saul, J. M., Tomblyn, S., Burnett, L., & Christ, G. J. (2017) · Tissue Engineering Part A · doi:10.1089/ten.tea.2016.0458 · Cited by 93 · see citing works
“57,71 73 Previous studies have shown that the incorporation of growth factors into keratin hydrogels permits controlled release over time.”
Self-citationAn improved method for solubilisation of wool keratin using peracetic acid
Shavandi, A., Carne, A., Bekhit, A. A., & Bekhit, A. E.-D. A. (2017) · Journal of environmental chemical engineering · doi:10.1016/j.jece.2017.03.043 · Cited by 94 · see citing works
Han, S., Ham, T. R., Haque, S., Sparks, J. L., & Saul, J. M. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.05.013 · Cited by 91 · see citing works
“It has also previously observed that rates of therapeutic agent release correlate with the rates of keratin hydrogel erosion [21,22].”
BackgroundSelf-citationCellulose, Chitosan, and Keratin Composite Materials. Controlled Drug Release
Tran, C. D., & Mututuvari, T. M. (2014) · Langmuir · doi:10.1021/la5034367 · Cited by 91 · see citing works
Therapeutics and delivery vehicles for local treatment of osteomyelitis
Cobb, L. H., McCabe, E. M., & Priddy, L. B. (2020) · Journal of Orthopaedic Research® · doi:10.1002/jor.24689 · Cited by 86 · see citing works
“Some natural materials that constitute hydrogels include, but are not limited to: alginate,(42,98,99) chitosan,(100) silk,(94) gelatin,(101,102) and keratin.(103) Alternatively, synthetic materials can be used, including: poly(acrylic acid),(101,104) poly(lactic‐co‐glycolic acid) (PLGA),(105) and PEG.”
BackgroundBiological importance and pharmaceutical significance of keratin: A review
Sarma, A. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.08.002 · Cited by 87 · see citing works
Esparza, Y., Bandara, N., Ullah, A., & Wu, J. (2018) · Materials Science and Engineering C · doi:10.1016/j.msec.2018.04.067 · Cited by 82 · see citing works
Tomblyn, S., Kneller, E. L. P., Walker, S. J., Ellenburg, M. D., Kowalczewski, C. J., Dyke, M. E. V., Burnett, L., & Saul, J. M. (2015) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.33438 · Cited by 78 · see citing works
Self-citationPark, M., Kim, B., Shin, H. K., Park, S., & Kim, H. Y. (2013) · Materials Science and Engineering C · doi:10.1016/j.msec.2013.08.032 · Cited by 77 · see citing works
Poranki, D. R., Whitener, W., Howse, S., Mesen, T., Howse, E., Burnell, J. M., Greengauz-Roberts, O. K., Molnar, J. A., & Dyke, M. E. V. (2013) · Journal of Biomaterials Applications · doi:10.1177/0885328213513310 · Cited by 71 · see citing works
Self-citationFabrication of keratin-silica hydrogel for biomedical applications
Kakkar, P., & Madhan, B. (2016) · Materials Science and Engineering C · doi:10.1016/j.msec.2016.04.067 · Cited by 71 · see citing works
Arafat, M. T., Mahmud, M. M., Wong, S. Y., & Li, X. (2020) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2020.102297 · Cited by 71 · see citing works
Keratin biomaterials augment anti-inflammatory macrophage phenotype in vitro
Waters, M., VandeVord, P. J., & Dyke, M. E. V. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.10.042 · Cited by 70 · see citing works
Self-citationDevelopment and assessment of kerateine nanoparticles for use as a hemostatic agent
Luo, T., Hao, S., Chen, X., Wang, J., Yang, Q., Wang, Y., Weng, Y., Wei, H., Zhou, J., & Wang, B. (2016) · Materials Science and Engineering C · doi:10.1016/j.msec.2016.03.007 · Cited by 68 · see citing works
Tran, C. D., Prosenc, F., Franko, M., & Benzi, G. (2016) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2016.06.021 · Cited by 66 · see citing works
Baker, H. B., Passipieri, J. A., Siriwardane, M. L., Ellenburg, M. D., Vadhavkar, M., Bergman, C. R., Saul, J. M., Tomblyn, S., Burnett, L., & Christ, G. J. (2017) · Tissue Engineering Part A · doi:10.1089/ten.tea.2016.0457 · Cited by 67 · see citing works
“In this regard, keratin is a viable candidate for VML repair due to its capacity to serve as an injectable cell and drug delivery vehicle.(26,28,31,32,35,37) As alluded to above, there is now a significant extant literature documenting that the inclusion of a cellular component in TE strategies for VML repair provides…”
BackgroundSelf-citationSustainable and smart keratin hydrogel with pH-sensitive swelling and enhanced mechanical properties
Ramos, M. L. P., González, J. A., Fabián, L., Pérez, C. J., Villanueva, M. E., & Copello, G. J. (2017) · Materials Science and Engineering C · doi:10.1016/j.msec.2017.04.120 · Cited by 63 · see citing works
Advances in Protein-Based Materials: From Origin to Novel Biomaterials
Choi, S. M., Chaudhry, P., Zo, S. M., & Han, S. S. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-0950-2_10 · Cited by 63 · see citing works
The Pharmacology of Regenerative Medicine
Christ, G. J., Saul, J. M., Furth, M. E., & Andersson, K. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.007393 · Cited by 61 · see citing works
Self-citationTransglutaminase‐modified wool keratin film and its potential application in tissue engineering
Cui, L., Gong, J., Fan, X., Wang, P., Wang, Q., & Qiu, Y. (2012) · Engineering in Life Sciences · doi:10.1002/elsc.201100206 · Cited by 59 · see citing works
“[28] reported the delivery and activity of the antibiotic ciprofloxacin from keratin hydrogels fabricated from human hair keratin proteins obtained by oxidative extraction, and concluded that the rate of ciprofloxacin release was highly correlated with the degradation of the keratin hydrogel and not consistent with si…”
BackgroundKowalczewski, C. J., Tombyln, S., Wasnick, D. C., Hughes, M. R., Ellenburg, M. D., Callahan, M. F., Smith, T. L., Van Dyke, M. E., Burnett, L. R., & Saul, J. M. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.12.087 · Cited by 58 · see citing works
“Furthermore, we have previously observed, and confirmed in this report, a correlation between the rate of hydrogel degradation and the rate of therapeutic agent delivery [21,22].”
Self-citationLi, Y., Wang, Y., Ye, J., Yuan, J., & Xiao, Y. (2016) · Materials Science and Engineering C · doi:10.1016/j.msec.2016.05.117 · Cited by 57 · see citing works
Roy, D. C., Tomblyn, S., Zuniga, K., Kowalczewski, C. J., Burmeister, D. M., Burnett, L., & Christy, R. J. (2016) · Wound Repair and Regeneration · doi:10.1111/wrr.12449 · Cited by 57 · see citing works
Roy, D. C., Tomblyn, S., Burmeister, D. M., Wrice, N. L., Becerra, S. C., Burnett, L., Saul, J. M., & Christy, R. J. (2014) · Advances in Wound Care · doi:10.1089/wound.2014.0576 · Cited by 56 · see citing works
“aureus) bacteria growth when loaded into keratose hydrogels.(23) Additionally, P.”
InfluentialSelf-citationLi, Y., Lin, J., Zhi, X., Li, P., Jiang, X., & Yuan, J. (2018) · Materials Science and Engineering C · doi:10.1016/j.msec.2018.05.073 · Cited by 56 · see citing works
Suarato, G., Contardi, M., Perotto, G., Heredia‐Guerrero, J. A., Fiorentini, F., Ceseracciu, L., Pignatelli, C., Debellis, D., Bertorelli, R., & Athanassiou, A. (2020) · Materials Science and Engineering C · doi:10.1016/j.msec.2020.111151 · Cited by 52 · see citing works
The Hair Follicle: An Underutilized Source of Cells and Materials for Regenerative Medicine
Kiani, M. T., Higgins, C. A., & Almquist, B. D. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.7b00072 · Cited by 50 · see citing works
Keratose/poly (vinyl alcohol) blended nanofibers: Fabrication and biocompatibility assessment
Wang, J., Hao, S., Luo, T., Zhou, T., Yang, X. H., & Wang, B. (2016) · Materials Science and Engineering C · doi:10.1016/j.msec.2016.11.071 · Cited by 48 · see citing works
Zhi, X., Wang, Y., Li, P., Yuan, J., & Shen, J. (2015) · RSC Advances · doi:10.1039/c5ra16253j · Cited by 43 · see citing works
Development of keratin-based membranes for potential use in skin repair
Navarro, J., Swayambunathan, J., Lerman, M. J., Santoro, M., & Fisher, J. P. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.10.025 · Cited by 42 · see citing works
“[28] for the sustained release of bioactive ciprofloxacin from keratin hydrogels, while we expect to use the high ED hydrogels for sustained use as membranes that should have lower effects on diffusion applications.”
BackgroundMethodKeratin-Based Biofilms, Hydrogels, and Biofibers
McLellan, J., Thornhill, S. G., Shelton, S. D., & Kumar, M. (2018) · Springer series on polymer and composite materials · doi:10.1007/978-3-030-02901-2_7 · Cited by 40 · see citing works
Sharma, G., Thakur, B., Kumar, A., Sharma, S., Naushad, M., & Stadler, F. J. (2020) · Macromolecular Materials and Engineering · doi:10.1002/mame.202000274 · Cited by 40 · see citing works
Navarro, J., Clohessy, R. M., Holder, R. C., Gabard, A. R., Herendeen, G. J., Christy, R. J., Burnett, L., & Fisher, J. P. (2019) · Tissue Engineering Part A · doi:10.1089/ten.tea.2019.0181 · Cited by 39 · see citing works
Enzymatic Extraction of Bioactive and Self‐Assembling Wool Keratin for Biomedical Applications
Su, C., Gong, J., Ye, J.-P., He, J., Li, R., Jiang, M., Geng, Y., Zhang, Y., Chen, J.-H., Xu, Z., et al. (2020) · Macromolecular Bioscience · doi:10.1002/mabi.202000073 · Cited by 39 · see citing works
Binding Interactions of Keratin-Based Hair Fiber Extract to Gold, Keratin, and BMP-2
de Guzman, R. C., Tsuda, S., Ton, M.-T. N., Zhang, X., Esker, A. R., & Dyke, M. E. V. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137233 · Cited by 36 · see citing works
Self-citationHalofuginone infused keratin hydrogel attenuates adhesions in a rodent cecal abrasion model.
Peyton, C., Keys, T., Tomblyn, S., Burmeister, D., Beumer, J., Holleran, J. L., Sirintrapun, J. S., Washburn, S., & Hodges, S. (2012) · Journal of Surgical Research · doi:10.1016/j.jss.2012.07.053 · Cited by 35 · see citing works
“Keratinwas extracted and prepared by an oxidative extraction process as previously described [18,19,23].”
BackgroundMethodInfluentialZhou, L.-T., Yang, G. Y., Yang, X., Cao, Z., & Zhou, M. (2014) · Environmental Science and Pollution Research · doi:10.1007/s11356-014-2513-8 · Cited by 34 · see citing works
“Some methods have been reported to dissolve keratin, mainly for wool sources, by using oxidizing or reducing reagents (Hamasaki et al. 2008; Saul et al. 2011), as well as ionic liquids (Li and Wang 2013).”
MethodComparative study of kerateine and keratose based composite nanofibers for biomedical applications
Yang, G. Y., Yao, Y., & Wang, X. (2017) · Materials Science and Engineering C · doi:10.1016/j.msec.2017.07.057 · Cited by 32 · see citing works
Fortunato, G. M., Ros, F. D., Bisconti, S., Acutis, A. D., Biagini, F., Lapomarda, A., Magliaro, C., Maria, C. D., Montemurro, F., Bizzotto, D., et al. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00174 · Cited by 31 · see citing works
“, 2013), drug delivery (Saul et al., 2011), haemostasis, and peripheral nerves repair (Wang et al.”
Human hair keratin-based biofilm for potent application to periodontal tissue regeneration
Lee, H., Hwang, Y., Lee, H., Choi, S., Kim, S. Y., Moon, J.-H., Kim, J. H., Kim, K. C., Han, D., Park, H., et al. (2015) · Macromolecular Research · doi:10.1007/s13233-015-3036-y · Cited by 30 · see citing works
Tesfaye, T., Sithole, B. B., & Ramjugernath, D. (2018) · International Journal of Chemical Sciences · doi:10.21767/0972-768x.1000281 · Cited by 30 · see citing works
“Recently it has been reported that 100% biodegradable packaging materials can be produced from renewable sources such as starch [2,6,14], proteins, cellulose, and rubber [15-20] and lipids [21-23].”
BackgroundHybrid antibacterial hydrogels based on PVP and keratin incorporated with lavender extract
Tajik, F., Eslahi, N., Rashidi, A., & Rad, M. M. (2021) · Journal of Polymer Research · doi:10.1007/s10965-021-02681-0 · Cited by 27 · see citing works
“Previous studies have found that keratin-based hydrogels can sustain the release of drugs and growth factors in correlation with their degradation [31, 43, 44].”
BackgroundCao, G. S., Zhang, Z. P., Rong, M. Z., & Zhang, M. Q. (2022) · SusMat · doi:10.1002/sus2.46 · Cited by 26 · see citing works
Noble, M. L., Mourad, P. D., & Ratner, B. D. (2014) · Biomaterials Science · doi:10.1039/c3bm60203f · Cited by 26 · see citing works
Kong, F., Mehwish, N., Niu, X., Lin, M., Rong, X., Hu, F., & Lee, B. H. (2021) · Materials Today Chemistry · doi:10.1016/j.mtchem.2021.100612 · Cited by 25 · see citing works
Ovomucin nanoparticles: promising carriers for mucosal delivery of drugs and bioactive compounds
Akbari, A., & Wu, J. (2017) · Drug Delivery and Translational Research · doi:10.1007/s13346-017-0406-3 · Cited by 25 · see citing works
Biopolymers and biocomposites: Nature’s tools for wound healing and tissue engineering
Osmani, R. A. M., Singh, E., Jadhav, K. V., Jadhav, S., & Banerjee, R. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820484-9.00023-4 · Cited by 24 · see citing works
Zuniga, K., Isaac, A., Christy, S., Wrice, N. L., Mangum, L. H., Natesan, S., Burnett, L., Christy, R. J., & Kowalczewski, C. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084100 · Cited by 23 · see citing works
“Keratin (KSO) was obtained by oxidative extraction of human hair and purified using a patented and controlled manufacturing process by KeraNetics, LLC (Winston-Salem, NC, USA) [42,43].”
MethodThe future perspectives of natural materials for pulmonary drug delivery and lung tissue engineering
Kim, S. Y., Wong, A. H. M., Neel, E. A. A., Chrzanowski, W., & Chan, H. (2014) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2015.993314 · Cited by 22 · see citing works
“The sustained drug release profile of ciprofloxacin from keratose hydrogels has been demonstrated to correlate with the hydrogel degradation rate [148].”
BackgroundIn vitro and in vivo Assessment of Keratose as a Novel Excipient of Paclitaxel Coated Balloons
Turner, E. A., Erwin, M. M., Atigh, M. K., Christians, U., Saul, J. M., & Yazdani, S. K. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00808 · Cited by 21 · see citing works
Self-citationKeratin-based matrices from wool fibers and human hair
Patrucco, A., Visai, L., Fassina, L., Magenes, G., & Tonin, C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816872-1.00013-3 · Cited by 21 · see citing works
Keratose hydrogel for tissue regeneration and drug delivery
Ledford, B. T., Barron, C., Dyke, M. E. V., & He, J. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.06.017 · Cited by 19 · see citing works
Self-citationH omo‐ and heteropolymer self‐assembly of recombinant trichocytic keratins
Parker, R. N., Roth, K. L., Kim, C., McCord, J. P., Dyke, M. E. V., & Grove, T. Ž. (2017) · Biopolymers · doi:10.1002/bip.23037 · Cited by 18 · see citing works
Self-citationDesign of nanoconstructs that exhibit enhanced hemostatic efficiency and bioabsorbability
Eissa, R. A., Saafan, H. A., Ali, A. A., Ibrahim, K. M., Eissa, N. G., Hamad, M. A., Pang, C., Guo, H., Gao, H., Elsabahy, M., et al. (2022) · Nanoscale · doi:10.1039/d2nr02043b · Cited by 16 · see citing works
Cohen, D. J., Hyzy, S. L., Haque, S., Olson, L. C., Boyan, B. D., Saul, J. M., & Schwartz, Z. (2018) · Tissue Engineering Part A · doi:10.1089/ten.tea.2017.0471 · Cited by 15 · see citing works
“Although it is also possible that rhBMP-2 remains associated with the keratin after release, we have not found evidence of interaction between keratins and drug molecules after release.(44) Based on the low bioactivity, we also cannot rule out the possibility that more bioactive rhBMP-2 remains associated with the ker…”
BackgroundSelf-citationPre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
Goel, E., Erwin, M. M., Cawthon, C. V., Schaff, C., Fedor, N., Rayl, T., Wilson, O., Christians, U., Register, T. C., Geary, R. L., et al. (2020) · Molecules · doi:10.3390/molecules25071596 · Cited by 15 · see citing works
“with the degradation rate of the hydrogel material [30].”
BackgroundSelf-citationLedford, B. T., Simmons, J., Chen, M., Fan, H., Barron, C., Liu, Z., Dyke, M. E. V., & He, J. (2017) · Stem Cells and Development · doi:10.1089/scd.2016.0351 · Cited by 15 · see citing works
“After removal of low-molecular-weight contaminants, the keratin nanomaterial solution was concentrated against dilute buffer using the same 100 kDa membrane, frozen and lyophilized [19].”
InfluentialSelf-citationExtrusion 3D printing of keratin protein hydrogels free of exogenous chemical agents
Brodin, E., Boehmer, M., Prentice, A., Neff, E., McCoy, K., Mueller, J., Saul, J. M., & Sparks, J. L. (2022) · Biomedical Materials · doi:10.1088/1748-605x/ac7f15 · Cited by 14 · see citing works
“Nevertheless, keratin biomaterials have shown unique promise in controlled drug delivery [3, 4] and regenerative medicine [5–7] and possess interesting properties that motivate further investigation of their use in 3D printing applications.”
Self-citationHPLC–MS/MS method for quantification of paclitaxel from keratin containing samples
Turner, E. A., Stenson, A. C., & Yazdani, S. K. (2017) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2017.03.011 · Cited by 14 · see citing works
Tomycz, N. D., Payne, C., Cheng, B. C., Hiller, N. L., Eutsey, R. A., Whiting, D. M., & Averick, S. E. (2019) · Surgical Infections · doi:10.1089/sur.2019.075 · Cited by 14 · see citing works
“Moreover, ciprofloxacin has shown the ability to inhibit the growth of both Pseudomonas aeruginosa and Staphylococcus aureus when loaded into keratose hydrogels [31].”
A keratin-based microparticle for cell delivery
Thompson, M. A., Giuffre, A., McClenny, C., & Dyke, M. E. V. (2020) · Journal of Biomaterials Applications · doi:10.1177/0885328220951892 · Cited by 14 · see citing works
Self-citationKeratin Protein-Catalyzed Nitroaldol (Henry) Reaction and Comparison with Other Biopolymers
Häring, M., Pettignano, A., Quignard, F., Tanchoux, N., & Díaz, D. D. (2016) · Molecules · doi:10.3390/molecules21091122 · Cited by 14 · see citing works
“Recently, keratinous materials have attracted increasing attention as an important source of renewable biomaterials, especially since keratin wastes have been estimated to be more than 5 million tons per year [8], being used after degradation for different applications including scaffolds for tissue engineering [9,10]…”
BackgroundHuman Hair Keratin-Based Hydrogels in Regenerative Medicine: Current Status and Future Directions
Ashna, M., Senthilkumar, N., & Sanpui, P. (2023) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.3c00883 · Cited by 13 · see citing works
Stimuli-responsive Hydrogels for Targeted Antibiotic Delivery in Bone Tissue Engineering
Kumar, J., Tolepbergenova, M., Musayev, A., Aizhan, D., Бегимбекова, Л. М., Kumar, H., Gulnar, T., Kumar, P., & Khan, S. (2025) · AAPS PharmSciTech · doi:10.1208/s12249-025-03218-0 · Cited by 12 · see citing works
“Similarly, Kera-tin-derived hydrogels released ciprofloxacin over 3 weeks in a sustained manner, remained bioactive against Staphylococcus aureus , and showed potential for use in tissue engineering settings requiring infection control [198].”
Fabrication and biological evaluation in vivo of an injectable keratin hydrogel as filler materials
Shao-bo, X., Zhang, C., Zhang, A., Wang, H., Rao, H., & Zhang, Z. (2015) · Journal of Bioactive and Compatible Polymers · doi:10.1177/0883911515609941 · Cited by 12 · see citing works
Preparation of Keratin-Metal Complexes Derived from Different Treatments of Chicken Feather Waste
Aldred, A. K., Klungsupya, P., Charerntantanakul, W., Weichold, O., & Sillapawattana, P. (2023) · Waste and Biomass Valorization · doi:10.1007/s12649-023-02154-z · Cited by 11 · see citing works
Development and characterization of a biomimetic coating for percutaneous devices
Trent, A., & Dyke, M. E. V. (2019) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2019.110351 · Cited by 11 · see citing works
Self-citationParker, R. N., Trent, A., Roth, K. L., Dyke, M. E. V., & Grove, T. Ž. (2020) · Biomedical Materials · doi:10.1088/1748-605x/ab98e8 · Cited by 10 · see citing works
Self-citationUntapped potentials of hazardous nanoarchitectural biopolymers
Ali, M. A., & Gould, M. L. (2020) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2020.124740 · Cited by 8 · see citing works
Protein-based microneedles for biomedical applications: A systematic review
Barati, M., Hashemi, S., Tabatabaei, M. S., Chamgordani, N. Z., Mortazavi, S. M., & Moghimi, H. R. (2024) · Biomedical Microdevices · doi:10.1007/s10544-024-00701-6 · Cited by 8 · see citing works
Assessment of the Effects of Energy Density in Crosslinking of Keratin-Based Photo-Sensitive Resin
Navarro, J., Swayambunathan, J., Santoro, M., & Fisher, J. P. (2018) · International Seminar of Biomedical Engineering (SIB) · doi:10.1109/sib.2018.8467744 · Cited by 8 · see citing works
Pharmaceutical & Cosmetical Application of Keratin Protein Obtaining from Biowaste- A Review
Varma, G. G., Sonawane, P. R., & Bhide, S. S. (2018) · American Journal of PharmTech Research · doi:10.46624/ajptr.2018.v8.i5.002 · Cited by 7 · see citing works
“ Hydrogels are formed from keratins obtained by oxidative preparation are called as keratose.([64]) Keratin can be processed in various forms, some of which mentioned below.”
BackgroundDyke, M. E. V. (2016) · doi:10.1002/9781119126218.ch6 · Cited by 7 · see citing works
Self-citationSynthesis of keratin-based hydrogels and cryogels destined for environmental applications
Wattie, B. (2017) · eScholarship@McGill (McGill) · doi:10.82308/54764 · Cited by 6 · see citing works
Yalçın, D., & Top, A. (2022) · Iranian Polymer Journal · doi:10.1007/s13726-022-01058-4 · Cited by 5 · see citing works
Human Hair: Scaffold Materials for Regenerative Medicine
Chen, I., & Yu, J. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-3258-0_14 · Cited by 4 · see citing works
The Use of Keratin as Potential Biomaterial for Bio-Dental Applications
Sharma, A. (2020) · Open Access Journal of Biomedical Science · doi:10.38125/oajbs.000204 · Cited by 4 · see citing works
“[51] Human hair *, ** Keratin hydrogels Sustained release of antibiotic (drug delivery)”
BackgroundLow Concentration and High Transparency Keratin Hydrogel Fabricated via Cryoablation
Wang, X., Shi, Z., Zhao, L., & Shen, X. (2021) · Frontiers in Materials · doi:10.3389/fmats.2021.710175 · Cited by 4 · see citing works
Saul, J. M., Bohnert, J. S., O’Brien, M., Alnuaimi, S., Carnwath, T. P., Dunivan, Q., Coffin, D. W., & Smith, T. L. (2025) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-025-00747-4 · Cited by 3 · see citing works
Self-citationLedford, B. T., Chen, M., Dyke, M. E. V., Barron, C., Zhang, X., Cartaya, A., Zheng, Y., Ceylan, A., Goldstein, A. S., & He, J. (2023) · Stem Cell Reviews and Reports · doi:10.1007/s12015-023-10574-6 · Cited by 3 · see citing works
“Finally, the solution was frozen and lyophilized to obtained as a solid product of KOS powder [16, 35].”
BackgroundMethodSelf-citationBioproteins: Fabrication and Application
Khan, M. N., Islam, T., Alam, M. A., & Khan, R. A. (2016) · Taylor & Francis eBooks · doi:10.1081/e-ebpp-120049962 · Cited by 3 · see citing works
Filho, M. M. R., Mazotto, A. M., & Pinheiro, A. S. (2025) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2025.01.002 · Cited by 2 · see citing works
Carroll, E., Tarabokija, A., Chaudhry, H., Meer, A. S., & de Guzman, R. C. (2026) · Macromolecular Bioscience · doi:10.1002/mabi.202500541 · Cited by 2 · see citing works
Alanazi, Y. M., Ragib, A. A., Yin, C.-Y., Aboughaly, M., & El‐Harbawi, M. (2026) · Polymer Bulletin · doi:10.1007/s00289-026-06368-8 · Cited by 1 · see citing works
- Authors
- Saul, J. M., Ellenburg, M. D., de Guzman, R. C., & Dyke, M. V.
- Affiliations
- Virginia Tech - Wake Forest University School of Biomedical Engineering & Sciences (US)
- Wake Forest University Health Sciences (US)
- Corresponding author
- Saul, Justin M.
- ORCID
- Saul, Justin M.
- Venue
- Journal of Biomedical Materials Research Part A
- Publisher
- Wiley
- Published
- 2011-06-16
- Volume
- 98A
- Issue
- 4
- Pages
- 544-553
- ISSN
- 1549-3296 (ISSN-L)
- 1552-4965
- OpenAlex
- W2044217991
- Cited by
- 111
- References
- 45
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 7 · 2021: 7 · 2020: 14 · 2019: 6 · 2018: 13 · 2017: 14 · 2016: 13 · 2015: 7 · 2014: 10 · 2013: 4 · 2012: 4
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Biomedical Materials Research Part A (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
- Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
- Keywords
- keratin hydrogels, keratosis, ciprofloxacin, sustained drug release, antibiotic delivery, Staphylococcus aureus, antibacterial activity, hydrogel degradation, traumatic injury, infection control, tissue regeneration
- MeSH terms
- Animals, Anti-Infective Agents, Bacterial Infections, Biocompatible Materials, Ciprofloxacin, Delayed-Action Preparations, Drug Carriers, Humans, Keratins, Materials Testing, Mice, Inbred C57BL, Sheep, Hydrogels, Mice
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