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伴有感染的颅骨伤口重建:生物图案化骨形态发生蛋白2与血管内皮生长因子效果比较

Reconstruction of a Calvarial Wound Complicated by Infection: Comparing the Effects of Biopatterned Bone Morphogenetic Protein 2 and Vascular Endothelial Growth Factor.

作者信息

Brooker Jack E, Camison Liliana B, Bykowski Michael R, Hurley Ethan T, Yerneni Saigopalakrishna S, Campbell Phil G, Weiss Lee E, Mooney Mark P, Cray James, Gilbert James R, Cooper Gregory M, Losee Joseph E

机构信息

Department of Plastic Surgery, University of Pittsburgh.

University of Pittsburgh Medical Center.

出版信息

J Craniofac Surg. 2019 Jan;30(1):260-264. doi: 10.1097/SCS.0000000000004779.

Abstract

Bone morphogenetic protein 2 (BMP2) bioprinted on biological matrix induces osseous regeneration in large calvarial defects in rabbits, both uncomplicated and scarred. Healing in unfavorable defects scarred from previous infection is decreased due in part to the lack of vascularity. This impedes the access of mesenchymal stem cells, key to osseous regeneration and the efficacy of BMP2, to the wound bed. The authors hypothesized that bioprinted vascular endothelial growth factor (VEGF) would augment the osseous regeneration achieved with low dose biopatterned BMP2 alone. Thirteen New Zealand white rabbits underwent subtotal calvariectomy using a dental cutting burr. Care was taken to preserve the underlying dura. A 15 mm × 15 mm flap of bone was cut away and incubated in a 1 × 108 cfu/mL planktonic solution of S aureus before reimplantation. After 2 weeks of subsequent infection the flap was removed and the surgical wound debrided followed by 10 days of antibiotic treatment. On postoperative day 42 the calvarial defects were treated with acellular dermal matrix bioprinted with nothing (control), VEGF, BMP2, BMP2/VEGF combined. Bone growth was analyzed with serial CT and postmortem histology. Defects treated with BMP2 (BMP2 alone and BMP2/VEGF combination) showed significantly greater healing than control and VEGF treated defect (P < 0.5). Vascular endothelial growth factor treated defect demonstrated less healing than control and VEGF/BMP2 combination treatments achieved less healing than BMP2 alone though these differences were nonsignificant. Low dose BMP2-patterned acellular dermal matrix improves healing of scarred calvarial defects. Vascular endothelial growth factor at the doses applied in this study failed to increase healing.

摘要

生物打印在生物基质上的骨形态发生蛋白2(BMP2)可诱导兔大型颅骨缺损(无论有无并发症或瘢痕形成)的骨再生。先前感染形成瘢痕的不利缺损处的愈合会降低,部分原因是缺乏血管。这阻碍了间充质干细胞(骨再生的关键以及BMP2发挥功效的关键)进入伤口床。作者推测,生物打印的血管内皮生长因子(VEGF)会增强仅使用低剂量生物图案化BMP2所实现的骨再生。13只新西兰白兔使用牙科切割钻进行了颅骨次全切除术。注意保留下方的硬脑膜。切下一块15毫米×15毫米的骨瓣,在1×108 cfu/mL的金黄色葡萄球菌浮游溶液中孵育,然后再植入。在随后2周的感染后,移除骨瓣并清创手术伤口,随后进行10天的抗生素治疗。术后第42天,用无任何打印物(对照)、VEGF、BMP2、BMP2/VEGF组合的脱细胞真皮基质治疗颅骨缺损。通过系列CT和死后组织学分析骨生长情况。用BMP2治疗的缺损(单独使用BMP2和BMP2/VEGF组合)显示出比对照和VEGF治疗的缺损明显更好的愈合效果(P<0.5)。VEGF治疗的缺损显示出比对照更少的愈合,VEGF/BMP2组合治疗比单独使用BMP2的愈合更少,尽管这些差异不显著。低剂量BMP2图案化的脱细胞真皮基质可改善瘢痕性颅骨缺损的愈合。本研究中应用的剂量的血管内皮生长因子未能增加愈合。

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