Ripamonti U, Van Den Heever B, Sampath T K, Tucker M M, Rueger D C, Reddi A H
Bone Research Laboratory, Medical Research Council/University of the Witwatersrand, Medical School, Johannesburg, South Africa.
Growth Factors. 1996;13(3-4):273-89,color plates III-VIII,pre.bk. doi: 10.3109/08977199609003228.
We examined the efficacy of a single application of recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7) for its ability to regenerate large calvarial defects in adult male baboons (Papio ursinus). Recombinant hOP-1, in conjunction with baboon or bovine guanidinium-extracted insoluble collagenous bone matrix (0.1, 0.5 and 2.5 mg per g of collagenous matrix as carrier), was implanted in 46 calvarial defects surgically prepared in 14 baboons, whilst 18 defects were implanted with the carrier matrix without hOP-1. Specimens were harvested on d 15, 30, 90 and 365 and subjected to histomorphometry on serial undecalcified sections cut at 7 microm to study the temporal sequence of tissue morphogenesis after the single application of hOP-1. Histological analysis indicated that the induction of new bone formation proceeded from the periphery to the central core of hOP-1 treated specimens after rapid angiogenesis and mesenchymal cell migration in apposition to the collagenous matrix. Whilst chondrogenesis was limited, newly formed bone has already filled with fully differentiated bone marrow elements as early as d 15, even with the 0.1 mg dose of hOP-1. On d 30 and 90, doses of 0.1 and 0.5 mg of hOP-1 showed greater amounts of bone than controls, and on d 90, they induced complete regeneration of the defects. Doses of 2.5 mg hOP-1 per g of matrix induced extensive osteogenesis initially with heterotopic ossification and displacement of the temporalis muscle above the defects. One year after implantation of hOP-1 there was restoration of the internal and external cortices of the calvaria. These results show that hOP-1 induces complete regeneration of calvarial bone in the adult primate, and suggest that the optimal activity of hOP-1 to achieve regeneration is between 100 and 500 microg of hOP-1 per g of matrix. These results in the primate may form the scientific basis for future clinical applications of hOP-1.
我们研究了单次应用重组人骨生成蛋白-1（hOP-1，骨形态发生蛋白-7）在成年雄性狒狒（豚尾狒狒）中再生大型颅骨缺损的能力。将重组hOP-1与狒狒或牛胍提取的不溶性胶原骨基质（每克胶原基质0.1、0.5和2.5毫克作为载体）联合，植入14只狒狒手术制备的46个颅骨缺损中，而18个缺损仅植入不含hOP-1的载体基质。在第15、30、90和365天采集标本，对7微米厚的连续不脱钙切片进行组织形态计量学分析，以研究单次应用hOP-1后组织形态发生的时间顺序。组织学分析表明，在与胶原基质并列的快速血管生成和间充质细胞迁移后，hOP-1处理标本的新骨形成诱导从周边向中央核心进行。虽然软骨生成有限，但早在第15天，即使是0.1毫克剂量的hOP-1，新形成的骨中也已充满完全分化的骨髓成分。在第30天和90天，0.1和0.5毫克剂量的hOP-1显示出比对照组更多的骨，并且在第90天，它们诱导缺损完全再生。每克基质2.5毫克hOP-1的剂量最初诱导广泛的骨生成，并伴有异位骨化和颞肌在缺损上方移位。hOP-1植入一年后，颅骨的内外皮质得以恢复。这些结果表明，hOP-1可诱导成年灵长类动物颅骨完全再生，并表明hOP-1实现再生的最佳活性为每克基质100至500微克hOP-1。灵长类动物的这些结果可能为hOP-1未来的临床应用奠定科学基础。
