Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA.
Department of Biological Sciences, North Dakota State University, Fargo, ND 58102, USA.
Int J Mol Sci. 2021 Jul 20;22(14):7736. doi: 10.3390/ijms22147736.
While the infection rate after primary total joint replacements (TJR) sits at 1-2%, for trauma-related surgery, it can be as high as 3.6 to 21.2% based on the type of trauma; the risk of reinfection after revision surgery is even higher. Current treatments with antibiotic-releasing PMMA-based bone cement/ beads and/or systemic antibiotic after surgical debridement do not provide effective treatment due to fluctuating antibiotic levels at the site of infection, leading to insufficient local antibiotic concentration. In addition, non-biodegradable PMMA does not support bone regrowth in the debrided void spaces and often must be removed in an additional surgery. Here, we report a bioactive glass or bioglass (BG) substrate-based biodegradable, easy to fabricate "press fitting" antibiotic-releasing bone void filling (ABVF-BG) putty to provide effective local antibiotic release at the site of infection along with support for bone regeneration. The ABVF-BG putty formulation had homogenously distributed BG particles, a porous structure, and showed putty-like ease of handling. Furthermore, the ABVF-BG putty demonstrated in vitro antibacterial activity for up to 6 weeks. Finally, the ABVF-BG putty was biodegradable in vivo and showed 100% bacterial eradication (as shown by bacterial cell counts) in the treatment group, which received ABVF-BG putty, compared to the infection control group, where all the rats had a high bacterial load (4.63 × 10 ± 7.9 × 10 CFU/gram bone) and sustained osteomyelitis. The ABVF-BG putty also supported bone growth in the void space as indicated by a combination of histology, µCT, and X-ray imaging. The potential for simultaneous infection treatment and bone healing using the developed BG-based ABVF-BG putty is promising as an alternative treatment option for osteomyelitis.
虽然初次全关节置换术后（TJR）的感染率为 1-2%，但基于创伤类型，创伤相关手术的感染率可高达 3.6-21.2%；翻修手术后再次感染的风险更高。目前，在手术清创后使用抗生素释放型聚甲基丙烯酸甲酯（PMMA）基骨水泥/珠粒和/或全身抗生素治疗，并不能提供有效的治疗效果，因为感染部位的抗生素水平波动，导致局部抗生素浓度不足。此外，不可生物降解的 PMMA 不能支持清创后空腔中的骨再生，通常必须在另一次手术中去除。在这里，我们报告了一种基于生物活性玻璃或生物玻璃（BG）的可生物降解、易于制造的“压配式”抗生素释放骨空洞填充（ABVF-BG）腻子，以在感染部位提供有效的局部抗生素释放，并支持骨再生。ABVF-BG 腻子配方具有均匀分布的 BG 颗粒、多孔结构，且易于操作。此外，ABVF-BG 腻子在体外具有长达 6 周的抗菌活性。最后，ABVF-BG 腻子在体内可生物降解，并在接受 ABVF-BG 腻子治疗的治疗组中显示出 100%的细菌根除（如细菌细胞计数所示），而感染对照组中所有大鼠的细菌负荷都很高（4.63×10±7.9×10 CFU/克骨），并持续患有骨髓炎。ABVF-BG 腻子还通过组织学、µCT 和 X 射线成像的组合，支持在空腔中的骨生长。使用开发的基于 BG 的 ABVF-BG 腻子同时进行感染治疗和骨愈合的潜力很大，有望成为骨髓炎的一种替代治疗选择。
