Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (18): 2858-2864.doi: 10.3969/j.issn.2095-4344.1670

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Preparation and property analysis of drug-loaded sustained-release scaffold with antibacterial and anti-inflammatory roles

Wu Jianxin1, Luo Dan2, Li Kun3, Xu Ning4, Ye Xiaojian4 
  

  1. 1Department of Orthopedics, Hongkou Branch of Changhai Hospital, Shanghai 200081, China; 2Department of Nursing, Shanghai Navy Medical Center, Shanghai 200052, China; 3Department of Orthopedics, Central Hospital of Ezhou, Ezhou 436000, Hubei Province, China; 4Spinal Minimally Invasive Center, Shanghai Changzheng Hospital, Shanghai 200003, China
  • Received:2018-12-26 Online:2019-06-28 Published:2019-06-28
  • Contact: Wu Jianxin, Attending physician, Department of Orthopedics, Hongkou Branch of Changhai Hospital, Shanghai 200081, China
  • About author:Wu Jianxin, Master, Attending physician, Department of Orthopedics, Hongkou Branch of Changhai Hospital, Shanghai 200081, China
  • Supported by:

    the Research Project of Health and Family Planning Commission of Hongkou District, No. 1603-29 (to WJX)

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Abstract:

BACKGROUND: When handling the local infection of the soft tissue of the wound, systemic oral antibiotics due to local concentration is low, cannot satisfy the bacteriostatic needs of local trauma. Although local antibiotics spraying powder can get a temporary high concentration, it is difficult to obtain satisfactory antibacterial effect, and high concentrations of drugs play destructive effect on local tissues.
OBJECTIVE: To develop a drug-loaded sustained-release scaffold that can carry multiple drugs, so as to be used for the local antibacterial and anti-inflammatory treatment of trauma.
METHODS: Mesoporous silica nanoparticles loaded with drug microspheres were prepared by mixing levofloxacin, tinidazole and methylprednisone solution with mesoporous silica nanoparticles in a negative pressure suction device. According to the designed CAD model in advance, the layer upon layer porous network structure of mesoporous silica nanoparticles loaded with drug microspheres and poly lactide-glycolide acid was alternately printed by three-dimensional printer. Finally, the membrane drug-loaded composite scaffold was obtained (experimental group). Meanwhile, calcium phosphate porous ceramic scaffolds loaded with three drugs were served as control group. The drug loading rate of scaffolds was detected. The two kinds of scaffolds were respectively co-cultured with fibroblasts. The cell proliferation was detected by cell counting-kit 8 assay to evaluate the cytotoxicity of scaffolds. The two scaffolds were immersed in PBS, respectively, to detect the drug release rule in vitro. These scaffolds were applied to the soft tissue injury sites of New Zealand white rabbits (provided by the Laboratory Animal Center of the Navy Medical University). The liver and kidney function, blood samples and drug concentrations in the surrounding tissues were detected at postoperative different time points.
RESULTS AND CONCLUSION: (1) The drug loading rates of levofloxacin, tinidazole and methylprednisolone in the scaffold of the experimental group were 31.21%, 22.14% and 23.58%, respectively. The drug loading rates of the three drugs in the scaffold of the control group were 19.44%, 11.14% and 9.32%, respectively. (2) The cell proliferation rates of in the two kinds of scaffolds at different time points were more than 80%, with grade 1 cytotoxicity. (3) In vitro, the release of the three drugs in the scaffold of the control group was basically complete at 2 weeks, the release of levofloxacin in the scaffold of the experimental group was up to 10 weeks, and the release of tinidazole and methylprednisolone in the scaffold of the experimental group was up to 8 weeks. (4) In vivo, the release time of the three drugs in blood samples and local tissues in the experimental group was longer than that in the control group, and the effective release time of the drugs was more than 10 weeks. The scaffold of the experimental group had transient effect on the liver function of rabbits (5) In summary, the multi-drug sustained-release scaffolds are successfully prepared by three-dimensional printing technology, which is expected to achieve combined, high and continuous local antibacterial and anti-inflammatory effects in the local wound, and be effectively applied in the adjuvant treatment of various local wounds.

Key words: rapid prototyping, three-dimensional printing, drug-loaded sustained-release scaffold, trauma repair, mesoporous silica nanoparticles, poly lactid-glycolide acid

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