CHONDROITIN SULFATE HYDROGEL REINFORCED WITH MAGNESIUM OXIDE NANOPARTICLES

Abstract

Osteomyelitis is a serious infection of the bone caused by pyogenic organisms that spread through the bloodstream, fractures, or surgery. This chondroitin sulphate-based hydrogel can serve as an effective treatment modality for osteomyelitis. This hydrogel can be used as a means for bone tissue engineering while simultaneously overcoming the disadvantages of bone grafting. Due to its excellent biocompatibility, flexibility, designability, and multifunctionality, this material is an ideal candidate for bone tissue engineering. The added benefit of nanoparticles, flavonoids, and antibiotics in this material facilitates the treatment of infection. References: 1. Ahmed G, lshaque B, Rickert M, Folsch C. (2018). Allogeneic bone transplantation in hip revision surgery : indications and potential for reconstruction. Orthopade 47:52-66. 2. Ahola N, Veiranto M, Mannisto N, et al. (2012). Processing and sustained in vitro release of rifampicin containing composites to enhance the treatment of osteomyelitis. Biomatter 2:213-25. 3. Alvarez A, Fernandez L, Gutierrez D, et al. (2019). Methicillin-resistant staphylococcus aureus in hospitals: Latest trends and treatments based on bacteriophages. J Clin Microbiol 57:e01006-019. 4. Anagnostakos K, Schroder K. (2012). Antibiotic-impregnated bone grafts in orthopaedic and trauma surgery: a systematic review of the literature. Int J Biomater 2012:538061. 5. Anugraha A, Hughes LD, Pillai A. (2019). A novel technique for fabricating antibiotic- coated intramedullary nails using an antibiotic-loaded calcium sulphate hydroxyapatite bio-composite, Cerament-V. J Surg Case Rep 2019:327. 6. Asri R, Harun W, Samykano M, et al. (2017). Corrosion and surface modification on biocompatible metals: a review. Mater Sci Eng C 77:1261-74. 7. Beenken ICE, Campbell MJ, Campbell MJ, et al. (2021). Evaluation of a bone tiller scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect. Sci Rep 11:10254. 8. Beenken KE, Smith JK, Skinner RA, et al. (2014). Chitosan coating to enhance the therapeutic efficacy of calcium sulfate-based antibiotic therapy in the treatment of chronic osteomyelitis. J Biomater Appl 29:514-23 9. Berebichez-Fridman R, Montero-Olvera P, G6mez-Garcia R, Berebichez-Fastlicht E. (2017). An intramedullary nail coated with antibiotic and growth factor nanoparticles: an individualized state-of-the-art treatment for chroni^p^feomyelitis with bone defects. Med Hypotheses 105:63-8.

Specification

Field of the intervention:
The present invention relates to the fields of Oral and Maxillofacial Surgery and
pharmacotherapy, in which a hydrogel is delivered locally for the treatment of osteomyelitis
for ameliorating infection and enhancing bone formation.


Background of the invention:
Osteomyelitis (OM) is an inflammatory bone disease that is caused by an infecting
microorganism and leads to progressive bone destruction and loss. Antibiotic treatments
using drugs such as levofloxacin and vancomycin (VCM) are the traditional choice for
treating osteomyelitis to control bacterial infection. Treating osteomyelitis by oral or
intravenous administration of systemic antibiotic therapy, can be effective. However, the
effectiveness of some antibiotics as antimicrobials has limitations that include poor
penetrability, which prevents the drug from reaching the minimum inhibitory concentration
(MIC) level in bone tissue. In addition, high doses of antibiotics administered systemically
-can induce serious side-effects such-as ototoxicity-and nephrotoxicity. Given these
limitations, there is a clear need for the development of delivery carriers for controlled
antibiotic release to improve its antimicrobial activity and reduce side-effects. Local therapy
is rapidly developing as a promising tool for the treatment of several diseases such as tumors
and osteomyelitis. For drug delivery, hydrogels combine the advantages of minimally
invasive application, in situ polymerization, inherently adhesiveness, and sustained drug
release. Magnesium oxide (MgO) NPs are a kind of important magnesium-contained
compound that can be degraded in a physiological environment or chloride-contained
aqueous solution to produce magnesium ions and hydroxyl ions. Previous studies confirmed
that Mg ions combined with hydroxyl ions possessed antibacterial properties, and Mg ions in
suitable concentrations have osteogenic promotive properties, especially in the alkalescent
environment. Quercetin is a flavonoid abundantly found in fruits and vegetables. Animal
studies have found that the action of quercetin on bone is largely protective, known to inhibit
RANKL-mediated osteoclastogenesis, osteoblast apoptosis, oxidative stress and inflammatory response while promoting osteogenesis, angiogenesis, antioxidant expression,
adipocyte apoptosis and osteoclast apoptosis. Double antibiotic paste is a common antibiotic
consisting of ciprofloxacin and metronidazole, which is mainly known for its treatment in
external resorption and its effectiveness against E. Faecalis and Porphyromonas Gingival is.
This invention is a composite material containing materials that address the dual issue of
Summary:
The chondroitin sulphate-based hydrogel is a composite material prepared in the following
manner:
1. 10% chondroitin sulphate (10/100ml) solution is prepared and methacrylated 20 times
2. Double antibiotic paste (DAP), Quercitin and MgO are added in previously optimized
, quantities
3. This mixture is then crosslinked using the photoinitiator-Irgacure 2959
4. This results in the formation of a hydrogel.
5. This hydrogel can be locally delivered at the site of osteomyelitis



We claim,
]■. This invention will serve as a potential local drug delivery system for the treatment of
osteomyelitis.
2. The hydrogel will facilitate the sustained release of antibiotics to combat bone infection
3. The inherent adhesiveness of the hydrogel and its biological ability to degrade naturally
will reduce the risk of operative complications.
4. The nanoparticles present in the hydrogel will promote bone formation as well as exert an
antibacterial effect on the surroundings.
5. The flavonoids incorporated in the material will reduce bone resorption, inflammation,
and oxidative processes.
The numerous materials encompassing this-invention wilbsynergistically act to.produce a
positive bone-protective effect.

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