An Antibiotic-Releasing Bone Void Filling (ABVF) Putty for the Treatment of Osteomyelitis

Hasan, Raquib; Wohlers, Abbey; Shreffler, Jacob; Mulinti, Pranothi; Ostlie, Hunter; Schaper, Codi; Brooks, Benjamin D.; Brooks, Amanda E.

doi:10.3390/ma13225080

Cited by 9 publications

(8 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ultimately, the presence of both a macro and micro-pores as seen in the produced ABVF-BG putty would support bone tissue healing. In addition to that, the particle size distribution of the BG used in the AVBF-BG putty ranged from 175 to 425 μm; according to previous reports, bone graft substitute particle size ranges from 100 to 500 μm helped in more new bone formation compared to when smaller (<105 μm) or larger (1000–2000 μm) particle sizes were used [ 43 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

A Bioglass-Based Antibiotic (Vancomycin) Releasing Bone Void Filling Putty to Treat Osteomyelitis and Aid Bone Healing

Hasan

Schaner

Mulinti

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

While the infection rate after primary total joint replacements (TJR) sits at 1–2%, for trauma-related surgery, it can be as high as 3.6 to 21.2% based on the type of trauma; the risk of reinfection after revision surgery is even higher. Current treatments with antibiotic-releasing PMMA-based bone cement/ beads and/or systemic antibiotic after surgical debridement do not provide effective treatment due to fluctuating antibiotic levels at the site of infection, leading to insufficient local antibiotic concentration. In addition, non-biodegradable PMMA does not support bone regrowth in the debrided void spaces and often must be removed in an additional surgery. Here, we report a bioactive glass or bioglass (BG) substrate-based biodegradable, easy to fabricate “press fitting” antibiotic-releasing bone void filling (ABVF-BG) putty to provide effective local antibiotic release at the site of infection along with support for bone regeneration. The ABVF-BG putty formulation had homogenously distributed BG particles, a porous structure, and showed putty-like ease of handling. Furthermore, the ABVF-BG putty demonstrated in vitro antibacterial activity for up to 6 weeks. Finally, the ABVF-BG putty was biodegradable in vivo and showed 100% bacterial eradication (as shown by bacterial cell counts) in the treatment group, which received ABVF-BG putty, compared to the infection control group, where all the rats had a high bacterial load (4.63 × 106 ± 7.9 × 105 CFU/gram bone) and sustained osteomyelitis. The ABVF-BG putty also supported bone growth in the void space as indicated by a combination of histology, µCT, and X-ray imaging. The potential for simultaneous infection treatment and bone healing using the developed BG-based ABVF-BG putty is promising as an alternative treatment option for osteomyelitis.

show abstract

Section: Discussionmentioning

confidence: 99%

A Bioglass-Based Antibiotic (Vancomycin) Releasing Bone Void Filling Putty to Treat Osteomyelitis and Aid Bone Healing

Hasan

Schaner

Mulinti

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…The model antibiotic vancomycin is available in the form of salt as vancomycin HCl commercially. To entrap the drug in the hydrophobic core of the silk nanosphere, the hydrophobic form of the drug, a vancomycin-free base, was prepared according to the previously published method [ 32 ]. Initially V-HCl was dissolved in water at a concentration of 70 mg/mL.…”

Section: Methodsmentioning

confidence: 99%

Infection Responsive Smart Delivery of Antibiotics Using Recombinant Spider Silk Nanospheres

et al. 2021

Self Cite

View full text Add to dashboard Cite

Frequent and inappropriate usage of antibiotics has changed the natural evolution of bacteria by reducing susceptibility and increasing resistance towards antibacterial agents. New resistance mechanisms evolved in the response to host defenses and pharmaceutical interventions are threatening our ability to treat common infections, resulting in increased mortality. In the face of this rising epidemic, antibiotic drug discovery, which has long been overlooked by big pharma, is reaching a critical low. Thus, the development of an infection-responsive drug delivery system, which may mitigate multidrug resistance and preserve the lifetime of our current antibiotic arsenal, has garnered the attention of both popular science and funding agencies. The present work describes the development of a thrombin-sensitive linker embedded into a recombinant spider silk copolymer to create a nanosphere drug delivery vehicle. Recent studies have suggested that there is an increase in thrombin-like activity during Staphylococcus aureus infection; thus, drug release from this new “smart” nanosphere can be triggered in the presence of infection. A thrombin sensitive peptide (TSP) was synthesized, and the thrombin cleavage sensitivity was determined by HPLC. The results showed no cleavage of the peptide when exposed to human serum whereas the peptide was cleaved when incubated with S. aureus exudate. Subsequently, the peptide was coupled with a silk copolymer via EDC-NHS chemistry and formulated into nanospheres encapsulating antibiotic vancomycin. These nanospheres were evaluated for in vitro infection-responsive drug release and antimicrobial activity. Finally, the drug responsive nanospheres were assessed for efficacy in an in vivo septic arthritis model. Our study provides evidence that the protein conjugate was enzyme responsive and can be used to formulate targeted drug release to combat infections against multidrug-resistant bacterial strains.

show abstract

“…Then, 100 mM EDC [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride] and 200 mM NHS (N-Hydroxysuccinimide) were added to activate it, which enabled the chemical binding of TSP. Finally, the encapsulation of vancomycin was carried out using the method described in the paper available at [ 193 ].…”

Section: Spider Silk In Nanomedicinementioning

confidence: 99%

Review of Spider Silk Applications in Biomedical and Tissue Engineering

Branković,

Zivic,

Grujovic

et al. 2024

Biomimetics

View full text Add to dashboard Cite

This review will present the latest research related to the production and application of spider silk and silk-based materials in reconstructive and regenerative medicine and tissue engineering, with a focus on musculoskeletal tissues, and including skin regeneration and tissue repair of bone and cartilage, ligaments, muscle tissue, peripheral nerves, and artificial blood vessels. Natural spider silk synthesis is reviewed, and the further recombinant production of spider silk proteins. Research insights into possible spider silk structures, like fibers (1D), coatings (2D), and 3D constructs, including porous structures, hydrogels, and organ-on-chip designs, have been reviewed considering a design of bioactive materials for smart medical implants and drug delivery systems. Silk is one of the toughest natural materials, with high strain at failure and mechanical strength. Novel biomaterials with silk fibroin can mimic the tissue structure and promote regeneration and new tissue growth. Silk proteins are important in designing tissue-on-chip or organ-on-chip technologies and micro devices for the precise engineering of artificial tissues and organs, disease modeling, and the further selection of adequate medical treatments. Recent research indicates that silk (films, hydrogels, capsules, or liposomes coated with silk proteins) has the potential to provide controlled drug release at the target destination. However, even with clear advantages, there are still challenges that need further research, including clinical trials.

show abstract

An Antibiotic-Releasing Bone Void Filling (ABVF) Putty for the Treatment of Osteomyelitis

Cited by 9 publications

References 55 publications

A Bioglass-Based Antibiotic (Vancomycin) Releasing Bone Void Filling Putty to Treat Osteomyelitis and Aid Bone Healing

A Bioglass-Based Antibiotic (Vancomycin) Releasing Bone Void Filling Putty to Treat Osteomyelitis and Aid Bone Healing

Infection Responsive Smart Delivery of Antibiotics Using Recombinant Spider Silk Nanospheres

Review of Spider Silk Applications in Biomedical and Tissue Engineering

Contact Info

Product

Resources

About