Journal
ACS OMEGA
Volume 5, Issue 8, Pages 4302-4312Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsomega.9b04249
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Funding
- National Natural Science Foundation of China [81600766, 81800695]
- Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20161419]
- Shanghai Young Doctor Training Programme
- National Key R&D Program of China [2018YFC1106100, 2018YFC1106101]
- Science and Technology Commission of Shanghai [17DZ2260100]
- Natural Science Foundation of Shanghai [18ZR1401900]
- Thyroid Research Program of Young Doctors [2017-N-14]
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Bone tissue engineering has emerged as an effective alternative treatment to the problem of bone defect. To repair a bone defect, antibiosis and osteogenesis are two essential aspects of the repair process. By searching the literature and performing exploratory experiments, we found that beta defensin 2 (BD2), with bifunctional properties of antibiosis and osteogenesis, was a feasible alternative for traditional growth factors. The antimicrobial ability of BD2 against Staphylococcus aureus and Escherichia coli was studied by the spread plate and live/dead staining methods (low effective concentration of 20 ng/mL). BD2 was also demonstrated to enhance osteogenesis, with higher messenger RNA (mRNA) and protein expression of the osteogenic markers collagen I (Col1), runt-related transcription factor 2 (Runx2), osteopontin (Opn), and osteocalcin (Ocn) in vitro (1.5-2.5-fold increase compared with the control group in the most effective concentration group), which was consistent with the alkaline phosphatase (ALP) and alizarin red S (ARS) staining results. We implanted poly(sebacoyl diglyceride) (PSeD) combined with BD2 and rat bone tissue-derived mesenchymal stem cells (rBMSCs) under the back skin of rats and found that the inflammatory response was significantly lower with this combination than with the PSeD/rBMSCs scaffold without BD2 and the pure PSeD group and was similar to the control group. Importantly, when assessed in a critical-sized in vivo rat 8 m diameter calvaria defect model, a scaffold we developed combining bifunctional BD2 with porous organic polymer displayed an osteogenic effect that was 160-200% greater than the control group. The in vivo study results revealed a significant osteogenic response and antimicrobial effect and were consistent with the in vitro results. In summary, BD2 displayed a great potential of simultaneously promoting bone regeneration and preventing infection and could provide a viable alternative to traditional growth factors applied in bone defect repair.
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