In vivo evaluation of temperature‐responsive antimicrobial‐loaded <scp>PNIPAAm</scp> hydrogels for prevention of surgical site infection

Heffernan, John M.; Overstreet, Derek J.; Vernon, Brent L.; McLemore, Ryan; Nagy, Tamás; Moore, Rex C.; Badha, Vajra S.; Childers, Erin P.; Nguyen, Michael B.; Gentry, Daniel D.; Calara, Francis; Saunders, W. B.; Feltis, Tim; McLaren, A. C.

doi:10.1002/jbm.b.34894

Cited by 8 publications

(4 citation statements)

References 46 publications

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“…There will be a few physical changes within the infected microenvironment, such as reduced pH and locally elevated temperature. These physical stimuli have already been used to activate the release of antibiotics [ 56 , 85 , 86 ].…”

Section: Resultsmentioning

confidence: 99%

Smart Bacteria-Responsive Drug Delivery Systems in Medical Implants

Yang

Xue

Lai

et al. 2022

JFB

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With the rapid development of implantable biomaterials, the rising risk of bacterial infections has drawn widespread concern. Due to the high recurrence rate of bacterial infections and the issue of antibiotic resistance, the common treatments of peri-implant infections cannot meet the demand. In this context, stimuli-responsive biomaterials have attracted attention because of their great potential to spontaneously modulate the drug releasing rate. Numerous smart bacteria-responsive drug delivery systems (DDSs) have, therefore, been designed to temporally and spatially release antibacterial agents from the implants in an autonomous manner at the infected sites. In this review, we summarized recent advances in bacteria-responsive DDSs used for combating bacterial infections, mainly according to the different trigger modes, including physical stimuli-responsive, virulence-factor-responsive, host-immune-response responsive and their combinations. It is believed that the smart bacteria-responsive DDSs will become the next generation of mainstream antibacterial therapies.

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Section: Resultsmentioning

confidence: 99%

Smart Bacteria-Responsive Drug Delivery Systems in Medical Implants

Yang

Xue

Lai

et al. 2022

JFB

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“…[ 9 ] The use of synthetic polymers (such as polylactic acid) to load antibiotics or small molecule drugs is currently a common treatment mode because of its antibacterial ability, small inflammatory response, and degradability. [ 10 ] However, it still faces problems such as a narrow antimicrobial spectrum, susceptibility to drug resistance, and poor osteoinductive properties of grafts. Another strategy is to use electroactive or photodynamic materials for sterilization.…”

Section: Introductionmentioning

confidence: 99%

A Biomimetic Multifunctional Scaffold for Infectious Vertical Bone Augmentation

Zhang,

Li,

Guo

et al. 2024

Advanced Science

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The regenerative treatment of infectious vertical bone defects remains difficult and challenging today. Current clinical treatments are limited in their ability to control bacteria and infection, which is unfavorable for new bone formation and calls for a new type of material with excellent osteogenic and antibacterial properties. Here a multifunctional scaffold is synthesized that mimics natural bone nanostructures by incorporating silver nanowires into a hierarchical, intrafibrillar mineralized collagen matrix (IMC/AgNWs), to achieve the therapeutic goals of inhibiting bacterial activity and promoting infectious alveolar bone augmentation in rats and beagle dogs. An appropriate concentration of 0.5 mg mL−1 AgNWs is selected to balance biocompatibility and antibacterial properties. The achieved IMC/AgNWs exhibit a broad spectrum of antimicrobial properties against Gram‐negative Porphyromonas gingivalis and Gram‐positive Streptococcus mutans. When the IMC/AgNWs are cocultured with periodontal ligament stem cells, it possesses excellent osteoinductive activities under both non‐inflammatory and inflammatory conditions. By constructing a rat mandibular infected periodontal defect model, the IMC/AgNWs achieve a near‐complete healing through the canonical BMP/Smad signaling. Moreover, the IMC/AgNWs enhance vertical bone height and osseointegration in peri‐implantitis in beagle dogs, indicating the clinical translational potential of IMC/AgNWs for infectious vertical bone augmentation.

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“…In the early stages of bone infections, surgery may not be needed so the systemic treatment is the only solution with all its drawbacks specially if needed for long period of time. Some investigations in animals are available for the delivery of therapeutic agents using injectable in suite forming scaffolds to control inflammation and enhance new bone regeneration without performing surgery and most of them had beneficial effects [ 17 , 28 – 30 ].…”

Section: Introductionmentioning

confidence: 99%

Injectable systems of chitosan in situ forming composite gel incorporating linezolid-loaded biodegradable nanoparticles for long-term treatment of bone infections

Wassif

Elkheshen

Shamma

et al. 2023

Drug Deliv. and Transl. Res.

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The objective of the current study was to create an efficient, minimally invasive combined system comprising in situ forming hydrogel loaded with both spray-dried polymeric nanoparticles encapsulating linezolid and nanohydroxyapatite for local injection to bones or their close vicinity. The developed system was designed for a dual function namely releasing the drug in a sustained manner for long-term treatment of bone infections and supporting bone proliferation and new tissues generation. To achieve these objectives, two release sustainment systems for linezolid were optimized namely a composite in situ forming chitosan hydrogel and spray-dried PLGA/PLA solid nanoparticles. The composite, in situ forming hydrogel of chitosan was prepared using two different gelling agents namely glycerophosphate (GP) and sodium bicarbonate (NaHCO3) at 3 different concentrations each. The spray-dried linezolid-loaded PLGA/PLA nanoparticles were developed using a water-soluble carrier (PVP K30) and a lipid soluble one (cetyl alcohol) along with 3 types of dl-lactide and/or dl-lactide-co-glycolide copolymer using nano-spray-drying technique. Finally, the optimized spray-dried linezolid nanoparticles were incorporated into the optimized composite hydrogel containing nanohydroxy apatite (nHA). The combined hydrogel/nanoparticle systems displayed reasonable injectability with excellent gelation time at 37 °C. The optimum formulae sustained the release of linezolid for 7–10 days, which reveals its ability to reduce the frequency of injection during the course of treatment of bones infections and increase the patients’ compliance. They succeeded to alleviate the bone infections and the associated clinical, biochemical, radiological, and histopathological changes within 2–4 weeks of injection. As to the state of art in this study and to the best of our knowledge, no such complete and systematic study on this type of combined in situ forming hydrogel loaded with spray-dried nanoparticles of linezolid is available yet in literatures. Graphical Abstract

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In vivo evaluation of temperature‐responsive antimicrobial‐loaded PNIPAAm hydrogels for prevention of surgical site infection

Cited by 8 publications

References 46 publications

Smart Bacteria-Responsive Drug Delivery Systems in Medical Implants

Smart Bacteria-Responsive Drug Delivery Systems in Medical Implants

A Biomimetic Multifunctional Scaffold for Infectious Vertical Bone Augmentation

Injectable systems of chitosan in situ forming composite gel incorporating linezolid-loaded biodegradable nanoparticles for long-term treatment of bone infections

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