Combining local antibiotic delivery with heparinized nanohydroxyapatite/collagen bone substitute: A novel strategy for osteomyelitis treatment

Padrão, Tatiana; Coelho, Catarina C.; Costa, Paulo; Alegrete, Nuno; Monteiro, F.J.; Sousa, Susana R.

doi:10.1016/j.msec.2020.111329

Cited by 32 publications

(18 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the OH − vibrational and stretching modes were also evident at 633 and 3572 cm −1 . As expected, lattice water was also present in the samples and represented by the peak at 1638 cm −1 and the broad band 3200–3500 cm −1 [ 26 , 27 ]. Peaks at 877 and 1421 cm −1 were related with carbonate groups in the samples that can result from the CO 2 adsorption by apatite [ 29 ].…”

Section: Resultssupporting

confidence: 61%

“…The chemical composition of the samples was also investigated using FTIR to evaluate the presence of functional groups at the molecular level ( Figure 4 ). The spectra obtained for the three samples showed the hydroxyapatite characteristic peaks, particularly the phosphate groups at 473, 564, 603, 962, 1032 and 1094 cm −1 [ 26 , 27 ]. These phosphate group peaks can be related with an average particle size.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

In Vitro Biocompatibility Assessment of Nano-Hydroxyapatite

Kavasi

Coelho²,

Platania

et al. 2021

Nanomaterials

Self Cite

View full text Add to dashboard Cite

Hydroxyapatite (HA) is an important component of the bone mineral phase. It has been used in several applications, such as bone regenerative medicine, tooth implants, drug delivery and oral care cosmetics. In the present study, three different batches of a commercial nanohydroxyapatite (nHA) material were physicochemically-characterized and biologically-evaluated by means of cytotoxicity and genotoxicity using appropriate cell lines based on well-established guidelines (ISO10993-5 and OECD 487). The nHAs were characterized for their size and morphology by dynamic light scattering (DLS) and transmission electron microscopy (TEM) and were found to have a rod-like shape with an average length of approximately 20 to 40 nm. The nanoparticles were cytocompatible according to ISO 10993-5, and the in vitro micronucleus assay showed no genotoxicity to cells. Internalization by MC3T3-E1 cells was observed by TEM images, with nHA identified only in the cytoplasm and extracellular space. This result also validates the genotoxicity since nHA was not observed in the nucleus. The internalization of nHA by the cells did not seem to affect normal cell behavior, since the results showed good biocompatibility of these nHA nanoparticles. Therefore, this work is a relevant contribution for the safety assessment of this nHA material.

show abstract

Section: Resultssupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

In Vitro Biocompatibility Assessment of Nano-Hydroxyapatite

Kavasi

Coelho²,

Platania

et al. 2021

Nanomaterials

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, after 72 h of culture, the graph shows a cytotoxic effect of vancomycin ( p -value ≤ 0.0001) and gentamicin ( p -value ≤ 0.0001), as demonstrated by the decrease in viable cells compared with ‘cells only’. In detail, the results demonstrated the major cytotoxicity of gentamicin, as compared with vancomycin, replicating a well-known effect already reported in the literature [ 15 , 24 , 26 , 40 , 41 ].…”

Section: Resultssupporting

confidence: 84%

“…To overcome these issues, novel bioactive and resorbable materials, which are osteoconductive and don’t require a second removal intervention, have been recently considered for the local delivery of antibiotics in the prevention and treatment of osteomyelitis [ 19 , 20 , 21 , 22 ]. The materials most widely used in orthopedic surgery are injectable cements loaded with antibiotics [ 23 , 24 , 25 , 26 , 27 ], however, since these are only marginally porous, the diffusion of loaded antibiotics into the surrounding bone tissue is limited and are often unable to promote efficient cell penetration or growth of new bone. Between bioresorbable grafts, the usage of calcium sulfate as an antibiotic-carrier material has proven its efficiency, as well as its security, as a carrier substance [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Medicated Hydroxyapatite/Collagen Hybrid Scaffolds for Bone Regeneration and Local Antimicrobial Therapy to Prevent Bone Infections

et al. 2021

View full text Add to dashboard Cite

Microbial infections occurring during bone surgical treatment, the cause of osteomyelitis and implant failures, are still an open challenge in orthopedics. Conventional therapies are often ineffective and associated with serious side effects due to the amount of drugs administered by systemic routes. In this study, a medicated osteoinductive and bioresorbable bone graft was designed and investigated for its ability to control antibiotic drug release in situ. This represents an ideal solution for the eradication or prevention of infection, while simultaneously repairing bone defects. Vancomycin hydrochloride and gentamicin sulfate, here considered for testing, were loaded into a previously developed and largely investigated hybrid bone-mimetic scaffold made of collagen fibers biomineralized with magnesium doped-hydroxyapatite (MgHA/Coll), which in the last ten years has widely demonstrated its effective potential in bone tissue regeneration. Here, we have explored whether it can be used as a controlled local delivery system for antibiotic drugs. An easy loading method was selected in order to be reproducible, quickly, in the operating room. The maintenance of the antibacterial efficiency of the released drugs and the biosafety of medicated scaffolds were assessed with microbiological and in vitro tests, which demonstrated that the MgHA/Coll scaffolds were safe and effective as a local delivery system for an extended duration therapy—promising results for the prevention of bone defect-related infections in orthopedic surgeries.

show abstract

“…Later, Padrāo et al showed another heparinized nanohydroxyapatite and collagen-based bone substitute to deliver quantifiable vancomycin for 19 days. Although the authors showed that the day 1 release of vancomycin was bactericidal, they did not show if the released vancomycin at all timepoints were able to eradicate the bacteria [ 52 ]. Le Ray et al used vancomycin-loaded PCL particles to treat osteomyelitis in a rabbit model (10 7 CFU S. aureus inoculation) with a 2-log reduction in bacterial count after 110 days of treatment [ 53 ], although no osseointegrating material was used in this study.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

The number of total joint replacements (TJR) is on the rise with a corresponding increase in the number of infected TJR, which necessitates revision surgeries. Current treatments with either non-biodegradable, antibiotic-releasing polymethylmethacrylate (PMMA) based bone cement, or systemic antibiotic after surgical debridement do not provide effective treatment due to fluctuating antibiotic levels at the site of infection. Here, we report a biodegradable, easy-to-use “press-fitting” antibiotic-releasing bone void filling (ABVF) putty that not only provides efficient antibiotic release kinetics at the site of infection but also allows efficient osseointegration. The ABVF formulation was prepared using poly (D,L-lactide-co-glycolide) (PLGA), polyethylene glycol (PEG), and polycaprolactone (PCL) as the polymer matrix, antibiotic vancomycin, and osseointegrating synthetic bone PRO OSTEON for bone-growth support. ABVF was homogenous, had a porous structure, was moldable, and showed putty-like mechanical properties. The ABVF putty released vancomycin for 6 weeks at therapeutic level. Furthermore, the released vancomycin showed in vitro antibacterial activity against Staphylococcus aureus for 6 weeks. Vancomycin was not toxic to osteoblasts. Finally, ABVF was biodegradable in vivo and showed an effective infection control with the treatment group showing significantly higher bone growth (p < 0.001) compared to the control group. The potential of infection treatment and osseointegration makes the ABVF putty a promising treatment option for osteomyelitis after TJR.

show abstract

Combining local antibiotic delivery with heparinized nanohydroxyapatite/collagen bone substitute: A novel strategy for osteomyelitis treatment

Cited by 32 publications

References 51 publications

In Vitro Biocompatibility Assessment of Nano-Hydroxyapatite

In Vitro Biocompatibility Assessment of Nano-Hydroxyapatite

Medicated Hydroxyapatite/Collagen Hybrid Scaffolds for Bone Regeneration and Local Antimicrobial Therapy to Prevent Bone Infections

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

Contact Info

Product

Resources

About