Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul 16;13(7):1090.
doi: 10.3390/pharmaceutics13071090.

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

Manuela Mulazzi  1 , Elisabetta Campodoni  1 , Giada Bassi  1 , Monica Montesi  1 , Silvia Panseri  1 , Francesca Bonvicini  2 , Giovanna Angela Gentilomi  2   3 , Anna Tampieri  1 , Monica Sandri  1
Affiliations

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

Manuela Mulazzi et al. Pharmaceutics. .

Abstract

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.

Keywords: biomimetic materials; bone regeneration; gentamicin sulfate; local therapy; microbial bone infection; vancomycin hydrochloride.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme of the protocol for drug loading and release from the hybrid scaffold. The quantification of the released drug was evaluated at specific time points by UV-Vis analyses.
Figure 2
Figure 2
Chemical-physical characterizations of the four different scaffold formulations (MgHA/Coll 70/30, 60/40, 50/50, and Coll). (A) FTIR analyses, (B) XRD diffractograms, (C) TGA analyses, and (D) ESEM analyses: (Di) MgHA/Coll 70/30, (Dii) MgHA/Coll 60/40, (Diii) MgHA/Coll 50/50, and (Div) Coll, show scaffold porosity and a fibrous morphology typical of the collagen component, while (Di–Diii) highlights the uniform distribution of mineral MgHA nanoparticles.
Figure 3
Figure 3
(A) Evaluation of swelling behavior, in PBS and 37 °C, for all the scaffolds compositions (MgHA/Coll 70/30, 60/40, 50/50 and Coll). (B) Evaluation of percentage of scaffold degradation in PBS and 37 °C.
Figure 4
Figure 4
Gentamicin and vancomycin release profiles at 37 °C and PBS, from all scaffold compositions loaded with (A) 2.5 mg of gentamicin and (B) 5.0 mg of vancomycin, recorded from time zero to twenty days.
Figure 5
Figure 5
Comparison of the release profiles for GNT and VNC from MgHA/Coll 70/30 wt.% scaffolds.
Figure 6
Figure 6
Disk diffusion test results for S. aureus ATCC 25923 (A) and P. aeruginosa ATCC27853 (B). Samples 1,2: MgHA/Coll 70/30 + VNC; sample 3: VNC 10 µg; samples 4,5: MgHA/Coll 70/30 + GNC; sample 6: GNC 10 µg; samples 7,8: MgHA/Coll 70/30; sample 9: sterile paper disk.
Figure 7
Figure 7
(A) MTT assay. Quantitative analyses of cell viability on 2D in vitro MG63 cell cultures in the presence of free vancomycin and gentamicin after 24 and 72 h of culture. (**** p-value ≤ 0.0001). (B) PrestoBlue™ Cell Viability Reagent. Quantitative analysis of MG63 viability, cultured one day on the 3D medicated-MgHA/Coll scaffolds. (**** p-value ≤ 0.0001).
Figure 8
Figure 8
Qualitative cell viability analysis performed with a live/dead kit 1 day after seeding. Calcein AM labels living cells in green by using FITC filter (EX 465-495; BA 515-555), ethidium homodimer-1 labels dead cells in red by using TRITC filter (EX 515-565; BA 550-660). Scale bar: 200 μm.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Dvir T., Timko B.P., Kohane D.S., Langer R. Nanotechnological strategies for engineering complex tissues. Nat. Nanotechnol. 2010;6:13–22. doi: 10.1038/nnano.2010.246. - DOI - PMC - PubMed
    1. Gomes M., Rodrigues M., Domingues R., Reis R.L. Tissue Engineering and Regenerative Medicine: New Trends and Directions—A Year in Review. Tissue Eng. Part B Rev. 2017;23:211–224. doi: 10.1089/ten.teb.2017.0081. - DOI - PubMed
    1. Ma P.X. Biomimetic materials for tissue engineering. Adv. Drug Deliv. Rev. 2008;60:184–198. doi: 10.1016/j.addr.2007.08.041. - DOI - PMC - PubMed
    1. Wegst U.G., Bai H., Saiz E., Tomsia A.P., Ritchie R.O. Bioinspired structural materials. Nat. Mater. 2015;14:23–36. doi: 10.1038/nmat4089. - DOI - PubMed
    1. Tampieri A., Sandri M., Landi E., Sprio S., Valentini F., Boskey A. Synthetic biomineralisation yielding HA/collagen hybrid composite. Adv. Appl. Ceram. 2008;107:298–302. doi: 10.1179/174367608X314163. - DOI

LinkOut - more resources