United States Army Institute of Surgical Research, Extremity Trauma & Regenerative Medicine Task Area, 3400 Rawley E. Chambers Ave. Fort Sam Houston, TX 78234, USA.
Expert Opin Drug Deliv. 2011 Dec;8(12):1555-69. doi: 10.1517/17425247.2011.628655. Epub 2011 Oct 22.
Open fractures are plagued by high complication rates, among which infection and nonunion are the most common, leading to higher morbidity and poor patient outcomes. Despite meticulous surgical care and employment of adjunctive therapies, infection rates remain at 20%, due to the limitations of conventional therapies.
Persistent bacteria often survive initial debridement and treatment with antibiotics. Thus, the bone graft subsequently implanted to promote healing can be the nidus for infection. The principles of biofilm theory and the "race to the surface" have been applied to develop dual-purpose bone grafts that are protected by a sustained release of an antibiotic, thereby preventing bacterial colonization. A simultaneous sustained release of a recombinant human growth factor allows the defect to become vascularized and heal.
Current therapies fail to meet the challenges of open fractures. Tissue engineering and drug delivery approaches can address the challenges of healing large bone defects while protecting the implant from infection. When combined as an adjunctive therapy with existing clinical practices for management of open fractures, dual-purpose bone grafts that release both an antibiotic and a growth factor at biologically relevant time scales can potentially reduce infection rates and improve patient outcomes.
开放性骨折并发症发生率高,其中感染和骨折不愈合最为常见,导致发病率较高和患者预后不良。尽管进行了精细的手术护理和辅助治疗,由于常规治疗的局限性,感染率仍保持在 20%。
最初清创和抗生素治疗后,持续存在的细菌往往能够存活下来。因此,随后植入以促进愈合的骨移植物可能成为感染的病灶。生物膜理论和“向表面赛跑”的原则已被应用于开发双重用途的骨移植物,这些移植物通过抗生素的持续释放得到保护,从而防止细菌定植。同时持续释放重组人生长因子可使缺损血管化并愈合。
目前的治疗方法无法应对开放性骨折的挑战。组织工程和药物输送方法可以解决治疗大骨缺损的挑战,同时保护植入物免受感染。当与开放性骨折的现有临床实践相结合作为辅助治疗时,在生物学相关时间范围内同时释放抗生素和生长因子的双重用途骨移植物可能降低感染率并改善患者预后。