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一种基于生物玻璃的抗生素(万古霉素)释放型骨空洞填充糊剂,用于治疗骨髓炎和促进骨愈合。

A Bioglass-Based Antibiotic (Vancomycin) Releasing Bone Void Filling Putty to Treat Osteomyelitis and Aid Bone Healing.

机构信息

Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA.

Department of Biological Sciences, North Dakota State University, Fargo, ND 58102, USA.

出版信息

Int J Mol Sci. 2021 Jul 20;22(14):7736. doi: 10.3390/ijms22147736.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d9e/8304857/33a334688d1f/ijms-22-07736-g001.jpg

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