OSTEOGENIN, A BONE MORPHOGENETIC PROTEIN, ADSORBED ON POROUS HYDROXYAPATITE SUBSTRATA, INDUCES RAPID BONE DIFFERENTIATION IN CALVARIAL DEFECTS OF ADULT PRIMATES
OSTEOGENIN, A BONE MORPHOGENETIC PROTEIN, ADSORBED ON POROUS HYDROXYAPATITE SUBSTRATA, INDUCES RAPID BONE DIFFERENTIATION IN CALVARIAL DEFECTS OF ADULT PRIMATES
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DOI：
10.1097/00006534-199209000-00004
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发表时间：
1992-09-01
影响因子：
3.6
通讯作者：
REDDI, AH
中科院分区：
文献类型：
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作者：
RIPAMONTI, U;MA, SS;REDDI, AH
成骨素是一种骨形态发生蛋白，与不溶性胶原骨基质结合，通过体内诱导启动局部软骨内骨分化。本研究通过利用天然骨生成素对羟基磷灰石的亲和力，旨在构建一种递送系统，用于在成年灵长类动物不愈合的颅骨缺损中表达骨生成素的生物活性。暴露颅骨后，在 16 只成年雄性狒狒（Papio ursinus）身上制备 64 个直径 25 mm 的颅骨缺损。将珊瑚碳酸钙外骨骼水热转化后获得的多孔不可吸收和可吸收羟基磷灰石基质圆盘植入缺损处。在每只动物中，在肝素-琼脂糖、羟基磷灰石和Sephacryl S-200凝胶过滤柱上进行连续层析后，用从狒狒骨基质中分离和纯化的骨生成素处理每种羟基磷灰石制品的一个圆盘。其余两个缺损处植入各羟基磷灰石制剂的一个圆盘，不含骨生成素作为对照。第 30 天和第 90 天制备的脱钙切片的组织形态计量学显示，与对照相比，经骨生成素处理的不可吸收羟基磷灰石样本具有更好的成骨作用。第 90 天，对照不可吸收羟基磷灰石样本中也发生了大量骨形成。在第 90 天，但不是在第 30 天，与可吸收对照相比，经骨生成素处理的可吸收样本中形成的骨量显着增加。总体而言，与不可吸收基质相比，可吸收基质表现较差，这可能是由于植入物过早溶解所致。这些结果证明，骨生成素的生物活性可以通过有机胶原基质以外的基质恢复和传递，从而诱导成年非人灵长类动物颅骨缺损的快速骨分化。成骨素在多孔无机非免疫原性基质上的吸附策略可能有助于设计适合人类颅面和骨科应用的成骨递送系统。
Osteogenin, a bone morphogenetic protein, in conjunction with insoluble collagenous bone matrix initiates local endochondral bone differentiation by induction in vivo. This study, by exploiting the affinity of native osteogenin for hydroxyapatite, was designed to construct a delivery system for the expression of the biologic activity of osteogenin in nonhealing calvarial defects of adult primates. After exposure of the calvaria, 64 cranial defects, 25 mm in diameter, were prepared in 16 adult male baboons (Papio ursinus). Defects were implanted with disks of porous nonresorbable and resorbable hydroxyapatite substrata obtained after hydrothermal conversion of calcium carbonate exoskeletons of corals. In each animal, one disk of each hydroxyapatite preparation was treated with osteogenin isolated and purified from baboon bone matrix after sequential chromatography on heparin-Sepharose, hydroxyapatite, and Sephacryl S-200 gel filtration columns. The remaining two defects were implanted with one disk of each hydroxyapatite preparation without osteogenin as control. Histomorphometry on decalcified sections prepared on days 30 and 90 showed superior osteogenesis in osteogenin-treated nonresorbable hydroxyapatite specimens as compared with controls. On day 90, substantial bone formation also had occurred in control nonresorbable hydroxyapatite specimens. On day 90, but not on day 30, significantly greater amounts of bone had formed in osteogenin-treated resorbable specimens as compared with resorbable controls. Overall, resorbable substrata performed poorly when compared with nonresorbable substrata, perhaps due to a premature dissolution of the implants. These results provide evidence that the biologic activity of osteogenin can be restored and delivered by a substratum other than the organic collagenous matrix, inducing rapid bone differentiation in calvarial defects of adult nonhuman primates. The adsorption strategy of osteogenin on porous inorganic nonimmunogenic substrata may help to design appropriate osteogenic delivery systems for craniofacial and orthopedic applications in humans.