Abstract:
The need to promote calvaria bone healing as a consequence of injury or craniotomy is a major clinical issue. Previous reports tested recombinant human Jagged1 (rhJagged1) treatment for critical-size calvaria defects in the absence of periosteum, and this resulted in significant new bone formation. As the periosteum contributes to healing by serving as a source of progenitor cells, the present study aimed to examine whether significantly more bone is formed when the periosteum is intact for using rhJagged1 to treat critical-size parietal bone defects in mice. Fifteen healthy adult mice, 34 to 65 weeks of age, 26.9 to 48.2 g, were divided into different groups that compared the critical-size defects treated with either phosphate-buffered saline or rhJagged1 protein in either the presence or absence of periosteum. The results indicated that more bone was formed in the presence of periosteum when rhJagged1 is delivered [35% bone volume per tissue volume (BV/TV); P = 0.02] relative to nonperiosteum. Recombinant human Jagged1 protein delivered in the absence of periosteum had the next most new bone formed (25% BV/TV). Defects with phosphate-buffered saline delivered in the absence or presence of periosteum had the least new bone formed (15% and 18% BV/TV, respectively; P = 0.48). The results also show that rhJagged1 does not form ectopic or hypertrophic bone. The usage of rhJagged1 to treat critical-size defects in calvaria is promising clinically, but to maximize clinical efficacy it will require that the periosteum be intact on the noninjured portions of calvaria.
摘要:
由于损伤或开颅手术而需要促进颅骨愈合是主要的临床问题。以前的报告测试了重组人Jagged1(rhJagged1)在没有骨膜的情况下治疗临界大小的颅骨缺损,这导致了大量的新骨形成。由于骨膜作为祖细胞的来源有助于愈合,本研究旨在研究当骨膜完整时,使用rhJagged1治疗小鼠临界大小的顶骨缺损是否会形成更多的骨.15只健康的成年小鼠,34至65周龄,26.9至48.2g,分为不同的组,比较在存在或不存在骨膜的情况下用磷酸盐缓冲盐水或rhJagged1蛋白处理的临界尺寸缺陷。结果表明,当rhJagged1递送时,在存在骨膜的情况下形成了更多的骨骼[每组织体积35%的骨骼体积(BV/TV);相对于非骨膜,P=0.02]。在不存在骨膜的情况下递送的重组人Jagged1蛋白具有下一个新骨形成(25%BV/TV)。在不存在或存在骨膜的情况下,用磷酸盐缓冲盐水递送的缺损形成的新骨最少(15%和18%BV/TV,分别为;P=0.48)。结果还显示rhJagged1不形成异位或肥大骨。使用rhJagged1治疗颅骨的临界尺寸缺陷在临床上是有希望的,但为了最大限度地提高临床疗效,需要颅骨非损伤部位的骨膜完整。