From the Department of Plastic Surgery, University of Pittsburgh; Biomedical Engineering and Biological Sciences and The Robotics Institute, Carnegie Mellon University; and The Ohio State University College of Medicine.
Plast Reconstr Surg. 2019 Jun;143(6):1215e-1223e. doi: 10.1097/PRS.0000000000005640.
Large calvarial defects represent a major reconstructive challenge, as they do not heal spontaneously. Infection causes inflammation and scarring, further reducing the healing capacity of the calvaria. Bone morphogenetic protein-2 (BMP2) has been shown to stimulate osteogenesis but has significant side effects in high doses. BMP2 has not been tested in combination with antiinflammatory cytokines such as interleukin-10.
Sixteen New Zealand White rabbits underwent 15 × 15-mm flap calvarectomies. The flap was incubated in Staphylococcus aureus and replaced, and infection and scarring were allowed to develop. The flap was subsequently removed and the wound débrided. A 15 × 15-mm square of acellular dermal matrix biopatterned with low-dose BMP2, interleukin-10, or a combination was implanted. Computed tomographic scans were taken over 42 days. Rabbits were then killed and histology was performed.
Defects treated with BMP2 showed significantly (p < 0.05) greater osseous regeneration than untreated controls. Interleukin-10 did not significantly augment the healing achieved with BMP2, and interleukin-10 alone did not significantly increase healing compared with controls. Histology showed evidence of bone formation in defects treated with BMP2. Untreated controls and defects treated with interleukin-10 alone showed only fibrous tissue in the defect site.
Low-dose BMP2 delivered directly to the scarred calvarial defect augments bony healing. Interleukin-10 at the dose applied did not significantly augment healing alone or in combination with BMP2. Healing had not finished at 42 days and analysis at later time points or the use of higher doses of BMP2 may yield greater healing.
大面积颅骨缺损是一个主要的重建挑战,因为它们不会自发愈合。感染会引起炎症和瘢痕形成,进一步降低颅骨的愈合能力。骨形态发生蛋白-2(BMP2)已被证明能刺激成骨,但在高剂量下有显著的副作用。BMP2 尚未与抗炎细胞因子如白细胞介素-10 联合测试过。
16 只新西兰白兔接受了 15×15-mm 皮瓣颅骨切除术。皮瓣孵育在金黄色葡萄球菌中,并进行了更换,允许感染和瘢痕形成。随后去除皮瓣,清创伤口。植入了一个 15×15-mm 的脱细胞真皮基质正方形,其形状为低剂量 BMP2、白细胞介素-10 或两者的组合。在 42 天内进行计算机断层扫描。然后杀死兔子并进行组织学检查。
用 BMP2 治疗的缺陷显示出明显(p < 0.05)比未治疗的对照组更高的骨再生。白细胞介素-10 并没有显著增强 BMP2 治疗的愈合效果,而且白细胞介素-10 单独使用与对照组相比也没有显著增加愈合效果。组织学显示在 BMP2 治疗的缺陷中有骨形成的证据。未治疗的对照组和仅用白细胞介素-10 治疗的缺陷仅在缺陷部位显示出纤维组织。
直接施用于瘢痕颅骨缺损的低剂量 BMP2 可增强骨愈合。在应用的剂量下,白细胞介素-10 单独使用或与 BMP2 联合使用都没有显著增强愈合效果。在 42 天内尚未完成愈合,进一步的分析或使用更高剂量的 BMP2 可能会产生更大的愈合效果。