Bone regeneration by recombinant human bone morphogenetic protein-2 and a novel biodegradable carrier in a rabbit ulnar defect model

The effects of recombinant human bone morphogenetic protein (rhBMP)-2 and a novel carrier, PLGA-coated gelatin sponge (PGS), on bone defect repair was examined. A 1.5 cm unilateral segmental bone defect was created in the ulnar diaphysis of a Japanese white rabbit. In an initial study, defects were either treated with PGS impregnated with various concentrations of rhBMP-2 (0, 0.1, 0.4 and 1 mg/cm(3)) or left untreated. Defect healing was assessed by radiographic union rate, and biomechanical properties of regenerated bones were determined at 16 weeks postoperatively. In a second study, defects were implanted with PGS with or without rhBMP-2, and histologically observed at postoperative weeks 8 and 16. Radiographic union rate increased the dose-dependently at an early time point. All defects treated with rhBMP-2 (0.4 and 1 mg/cm(3)) were radiographically repaired. Mechanical properties of regenerated bones were restored in a dose-dependent manner. Neither ulnae left untreated nor implanted PGS alone showed radiographic union. Longitudinal alignment of lamellar structure was observed histologically at 16 weeks, indicating that remodeling of regenerated bone was complete. Implanted PGS was almost completely resorbed by 8 weeks, and no abnormalities were observed in the surrounding soft tissue. These results suggest that PGS is a promising carrier for rhBMP-2.     

不同有机溶剂对缓释重组人骨形态发生蛋白2微胶囊的影响

背景：查阅文献发现在采用复乳溶剂挥发法制备缓释重组人骨形态发生蛋白2微胶囊的过程中,可以二氯甲烷、乙酸乙酯、丙酮或不同有机溶剂混合物等作为油相,而孰优孰劣尚无定论。 目的：优化包封重组人骨形态发生蛋白2微胶囊制备方法,比较不同有机溶剂对微胶囊产生的影响。 方法：分别以二氯甲烷(A组)、二氯甲烷与乙酸乙酯混合液(B组)、乙酸乙酯(C组)、乙酰丙酮(D组)等4种不同类型的有机溶剂作为油相,以聚乳酸-聚乙二醇-聚乳酸三嵌段共聚物为囊材,采用复乳溶剂挥发法制备缓释重组人骨形态发生蛋白2微胶囊,检测微囊的粒径、形态及包封率。将制备的微胶囊分别与第3代大鼠骨髓间充质干细胞共培养,培养14 d后检测碱性磷酸酶活性。 结果与结论：A组微囊形态均一规则,微囊粒径小(4-10 µm),包封率最高;B组、C组微囊粒径分布范围较大,包封率中等;D组微囊基本难成形,包封率最低。A组、B组、C组碱性磷酸酶活性明显高于D组(P < 0.05),A组、B组均明显高于C组(P < 0.05),A组与B组之间无明显差异。表明以二氯甲烷作为有机溶剂制备的重组人骨形态发生蛋白2微胶囊包封率高,形态优良且能很好地保护重组人骨形态发生蛋白2的生物活性。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

New scaffold for recombinant human bone morphogenetic protein-2

A bioactive and resorbable scaffold is necessary to exhibit the osteoinductive potency of recombinant human bone morphogenetic protein-2 (rhBMP-2). In a previous study, we found that synthetic octacalcium phosphate (OCP) enhances bone regeneration and is replaced by newly formed bone after it is resorbed. We hypothesized that OCP may be useful as an effective scaffold for rhBMP-2 to enhance bone regeneration. To test this hypothesis, the present study was designed to investigate whether an OCP/BMP composite implant could more effectively enhance bone regeneration. A critical-sized defect was made in a rat calvarium and 1. 15 mg of OCP combined with 10 microg of rhBMP-2 (OCP/BMP 10 microg), 2. 15 mg of OCP combined with 1 microg of rhBMP-2 (OCP/BMP 1 microg), or 3. OCP (OCP alone) was implanted into the defect and fixed at 4 or 8 weeks after implantation. The percentage of newly formed bone (n-Bone%) in the defect was determined by a histomorphometrical analysis. A statistical analysis showed that n-Bone% with OCP/BMP was significantly higher than that with OCP at both time points, whereas the difference in n-Bone% between OCP/BMP 10 microg and OCP/BMP 1 microg was not significant. The present results suggest that OCP can be used as an effective scaffold for rhBMP-2 and this OCP delivery system may be able to reduce the standard effective dose of rhBMP-2, which would be beneficial because low doses (<100 microg/g OCP) of rhBMP-2 enhance bone regeneration.     

人骨形态发生蛋白2基因修饰自体骨髓间充质干细胞移植促进兔下颌骨牵张成骨实验的组织形态学观察

背景：如何提高牵张成骨过程中新骨形成的速度和质量,缩短牵张成骨治疗时间,减少并发症的发生是目前该领域的研究热点。 目的：观察人骨形态发生蛋白2基因修饰自体骨髓间充质干细胞移植对兔下颌骨牵张成骨新骨形成的促进作用。 方法：36只新西兰白兔随机摸球法分为3组。建立牵张成骨动物模型,在固定期第2天,实验组于牵张间隙注射人骨形态发生蛋白2基因修饰的自体骨髓间充质干细胞;对照组注射等量自体骨髓间充质干细胞;空白组注射等量生理盐水。 结果与结论：在固定期2周及6周实验组牵张区骨小梁形成质量明显好于对照组和空白组。证实骨形态发生蛋白2基因修饰的自体骨髓间充质干细胞移植能有效促进兔下颌骨牵张成骨新骨形成。     

Restoration of segmental bone defects in rabbit radius by biodegradable capsules containing recombinant human bone morphogenetic protein-2

Recombinant human bone morphogenetic protein-2 (rhBMP-2) was encapsulated in biodegradable poly(DL-lactide-co-glycolide) (PLGA) capsules to regenerate bone by controlling the release rate of rhBMP-2. The rhBMP-2/PLGA capsules containing 12 microg of rhBMP-2 were implanted in seven 15-mm segmental defects of rabbits radii to examine the healing capacity of the rhBMP-2/PLGA capsules. For the control group, four segmental defects were left empty and two were implanted with ghost PLGA capsules. Healing of the defects was followed for 24 weeks and periodically evaluated by radiographs and histological examination. Mechanical testing was applied to three regenerated bone samples at 24 weeks postoperatively when the mature cortex was observed. Mechanical properties of regenerated bone were not significantly different from normal intact bone statistically. Histologically, the rhBMP-2/PLGA capsules disappeared completely during the process of bone regeneration. These results increased possibilities for clinical application of rhBMP-2/PLGA capsules.     

缓释型重组人骨形态发生蛋白2/壳聚糖生物骨修复材料诱导骨形成

背景：重组人骨形态发生蛋白2在体内半衰期短、易降解代谢,达不到理想的骨再生效果。 目的：制备缓释型重组人骨形态发生蛋白2/壳聚糖生物骨修复材料,并观察其缓释性能、骨诱导活性。 方法：将重组人骨形态发生蛋白2与壳聚糖混合制备壳聚糖膜,涂覆于生物骨修复材料表面,ELISA方法检测其体外释药性能。茜素红染色检测缓释型人骨形态发生蛋白2/壳聚糖生物骨材料、重组人骨形态发生蛋白2生物骨材料、单纯骨填充材料诱导C2C12细胞骨钙蛋白的形成,观察其诱导成骨细胞能力。同时将3种骨修复材料植入清洁级KM小鼠股部肌袋内,2周后检测新生骨Ca2+离子含量,评价其异位骨诱导能力。 结果与结论：材料表面的壳聚糖膜分布均匀,负载的重组人骨形态发生蛋白2呈团簇状。重组人骨形态发生蛋白2/壳聚糖生物骨修复材料体外释药存在突释,前4 d释放量达总药量的50%,持续至12 d,释药量达到90%,第18天时释放完全。与单纯骨填充材料、重组人骨形态发生蛋白2生物骨材料相比,缓释型人骨形态发生蛋白2/壳聚糖生物骨修复材料诱导C2C12细胞向成骨晚期分化能力与异位骨形成能力显著增强(P < 0.05)。结果提示缓释型人骨形态发生蛋白2/壳聚糖生物骨修复材料缓释性能好,促进骨形成能力强。     

重组人骨形态发生蛋白2/骨修复材料的制备与性能

BACKGROUND: It has become a hotspot to prepare the bone repair material that exhibits natural bone structure and is used in combination with biological factors. OBJECTIVE: To prepare the recombinant human bone morphogenetic protein-2 (rhBMP-2)/bone repair material, and to evaluate its capacities of release, activity and ectopic osteoinduction. METHODS: A collagen-binding domain was added to the N-terminal of native rhBMP-2 that allowed bind to collagens in the bone repair material. Then, rhBMP-2/bone repair material was obtained through freeze-dried method. The releasing ability of rhBMP-2 in vitro was assayed by ELISA. C2C12 cell lines were loaded to the composite material with 0.25, 0.5 and 1 µg rhBMP-2, respectively. Afterwards, alkaline phosphatase activity was detected at 72 hours. The composite materials with 0, 2, 5 and 10 µg rhBMP-2 were implanted into the quadriceps of Sprague-Dawley rats, respectively. Alkaline phosphatase activity and the newly formed bone were detected at 2 and 4 weeks after implantation. The CY-7-labeled composite material was implanted into the quadriceps of Sprague-Dawley rats to observe its stability. RESULTS AND CONCLUSION: Substantially no rhBMP-2 from the rhBMP-2/bone repair material was released within 45 days. The alkaline phosphatase activity of C2C12 was in a rise with the increased concentration of rhBMP-2. The stability of the composite material in vivo was better, the alkaline phosphatase activity and ectopic bone formation increased as the concentration of rhBMP-2 rose. To conclude, the rhBMP-2/bone repair material preserves the stability of rhBMP-2, and improves ectopic osteoinduction ability.     

Tissue reaction at the implantation of recombinant human bone morphogenetic protein-2 into the skeletal muscle

Bone morphogenetic protein (BMP) is a unique cytokine that induces bony tissue in soft tissue. Tissue reactions at and around the implantation of recombinant human BMP-2 (rhBMP-2) into the soft tissue of rats and nonhuman primates were investigated. At the osteoinduced site of rats, massive trabeculae-lined osteoblasts and rich marrow were observed. At and around the nonosteoinduced sites of nonhuman primates, large clear nuclei were observed in reaction to rhBMP-2 implantation. The surrounding area was visually classified into zones 1, 2 and 3. Zone 3 was near the center of the implant. The area of nuclei, the major axis, the minor axis and the ratio of minor axis per major axis were image-analyzed in the histological views. In zones 1, 2 and 3, the nuclear areas were 18.0 (3.1) mean (SD); unit micron2, 33.4 (5.61) and 110.1 (23.7), respectively. The major axes of nuclear ellipses were 7.45 (0.22) (unit micron), 7.76 (0.26), and 13.9 (1.88), respectively. The minor axes were 3.07 (0.53), 5.59 (0.95) and 10.1 (1.35), respectively. The ratios of minor axis per major axis of nuclear ellipses were 0.4 (0.57), 0.72 (0.11) and 0.73 (0.11) in zones 1, 2 and 3, respectively. These results showed that in zones 2 and 3 cell and tissue reactions were marked against rhBMP-2 implantation.     

人骨形态发生蛋白2基因重组腺病毒表达载体转染兔骨髓间充质干细胞*

背景：采用GatewayTM技术构建腺病毒载体,显著弥补了外源性细胞因子局部应用的缺陷。 目的：观察人骨形态发生蛋白2重组腺病毒表达载体(Ad-BMP-2/GFP)转染兔骨髓间充质干细胞后骨形态发生蛋白2的表达情况。 方法：密度梯度离心联合贴壁培养法,分离、培养、纯化兔骨髓间充质干细胞;GatewayTM技术构建的Ad-BMP-2/GFP腺病毒载体转染兔骨髓间充质干细胞。 结果与结论：RT-PCR检测转染诱导后的细胞表达成骨细胞特异性产物骨钙素;转染后兔骨髓间充质干细胞在mRNA水平和蛋白水平均有人骨形态发生蛋白2的表达。结果表明构建的Ad-BMP-2/GFP可高效转染兔骨髓间充质干细胞,骨形态发生蛋白2在细胞中能高效表达。     

Immobilized recombinant human bone morphogenetic protein-2 enhances the phosphorylation of receptor-activated Smads

Bone morphogenetic protein (BMP)-2 plays an important role in bone growth and regeneration; however, BMP-2 is easily lost by diffusion through body fluid and has some inhibitory pathways. To address this problem, we previously immobilized recombinant human BMP-2 (rhBMP-2) on succinylated type I atelocollagen. Here, we examined the effect of immobilized rhBMP-2 in vitro and vivo. In ST2, MC3T3-E1, and C2C12 cells, alkaline phosphatase activity, which is a marker of osteoblast differentiation, was enhanced more by immobilized than nonimmobilized rhBMP-2. In addition, the phosphorylation of receptor-activated Smads, part of the signaling pathway activated by BMP-2, was prolonged by immobilized rhBMP-2 in these cells. Furthermore, implantation of immobilized rhBMP-2 into the backs of rats promoted the formation of mature bone-like structure. These results demonstrate that immobilized rhBMP-2 has higher bioactivity than nonimmobilized rhBMP-2, and, therefore, immobilization of rhBMP-2 can prolong BMP signaling.     

人重组骨形态蛋白-2在脊柱融合中并发症的研究

自体骨移植物具有天然的骨诱导和骨传导特性,是骨移植材料中的金标准,但其存在局限性。目前重组人骨形态发生蛋白-2(rhBMP-2)被广泛应用于临床中以提高脊柱融合率。但其应用范围远超美国食品药品监督管理局(FDA)标准,同时也出现了很多并发症。因此研制出新型骨修复材料成为了目前亟待解决的问题。     

重组人骨形成蛋白-2-珊瑚人工骨复合物在拔牙窝牙槽骨修复中的作用

目的:探讨重组人骨形成蛋白-2与珊瑚人工骨复合物(复合骨 )在拔牙窝修复中的作用。方法:拔除 12只成年狗两侧上颌第二及第三切牙,并去除牙槽窝之间的牙槽间隔,一侧随即植入复合骨,对侧植入珊瑚人工骨(珊瑚骨 )作为对照。并于植入后 4、8、12周取材,采用组织学观察、图像分析和 [⁹⁹Tc^m]-MDP核素骨显像等方法比较两种植入材料在牙槽窝中的骨修复能力。结果:复合骨植入牙槽骨后,材料被逐渐降解吸收,新骨不断生成,12周后,植入材料完全被成熟的骨组织取代;图像分析结果显示不同时间复合骨组新骨形成的比值显著高于珊瑚骨组(P <0.05 );4和 8周复合骨组核素浓聚程度高于珊瑚骨组,12周两组核素浓聚程度差异不明显。结论:复合骨在牙槽骨缺损中的骨修复能力和修复效果明显优于珊瑚骨.     

重组人骨形态发生蛋白2诱导骨修复的应用及前景

背景：重组人骨形态发生蛋白2具备诱导成骨时间更早、成骨量较天然骨形态发生蛋白2多、生物学活性好、生物相容性好、成本低等特点,已成为近年来临床骨科创伤疾病防治研究的热点。 目的：总结重组人骨形态发生蛋白2在骨组织工程及骨修复领域应用中的优势、不足及目前国内外的研究进展。 方法：经第一作者检索CNKI数据库及SPRINGERLINK数据库2005至2011年与重组人骨形态发生蛋白2在诱导骨再生、骨组织修复有关研究进展方面的文献,英文检索词为“rhBMP-2,bone tissue engineering,bone repair materials”,中文检索词为“重组人骨形态发生蛋白2,骨组织工程,骨修复”。共检索出98篇,最终保留30篇进行归纳总结。 结果与结论：骨骼内天然骨形态发生蛋白2含量稀少、提取成本高昂,临床应用严重受限。重组人骨形态发生蛋白2有显著的成骨诱导能力,在骨组织工程及骨修复领域展现了巨大的潜在应用价值。体外试验无细胞毒性具有良好的生物相容性可供临床应用,其中重组人骨形态发生蛋白2和重组人骨形态发生蛋白7现已被应用于外科整形手术诱导骨再生,但由于重组人骨形态发生蛋白2是外源性细胞生长因子,临床应用多为超生理剂量,故潜在有软组织水肿,皮肤红疹、局部炎症反应、异位骨化和免疫反应等不良后果的危险,所以重组人骨形态发生蛋白2用于人体后的安全性研究还须长期密切关注。找到理想的载体,有效控制其在体内缓释是重组人骨形态发生蛋白2应用研究的关键问题。     

骨形态形成蛋白在下颌骨快速牵张成骨中的应用*

背景：牵张成骨已经成为治疗不同类型颅面畸形和骨缺损的有效的方法,但是牵张成骨的主要缺点是牵张期和稳定期比较长,可能导致牵张过程中严重的并发症。 目的：总结骨形态形成蛋白在快速牵张成骨过程中作用的研究现状。 方法：电子检索计算机Pubmed数据库(1989/2011)收录的骨形态形成蛋白和牵张成骨相关综述和论文报告。 结果与结论：共纳入骨形态形成蛋白在快速牵张成骨中的作用相关文献32篇。骨形态形成蛋白具有很强的成骨活性,能促进骨再生和骨改建。目前的研究显示应用骨形态形成蛋白能加快牵张成骨过程中新骨形成和缩短治疗的疗程。但是骨形态形成蛋白应用于临床还需要进一步的研究。     

重组人骨形成蛋白－2在大肠杆菌中的表达、纯化和复性

目的:通过对大肠杆菌表达重组人骨形成蛋白－2的复性研究,得到高活性的重组人骨形成蛋白－2。方法:在大肠杆菌中通过温度诱导表达重组人骨形成蛋白－2经过Triton X-100清洗之后,又通过DEAE离子交换层析纯化包涵体,包涵体在8 mol/L 尿素变性溶解,在氧化－还原(还原型和氧化型谷胱甘肽)复性系统中,通过简单的稀释复性,通过肝素亲和层析一步纯化法纯化重组人骨形成蛋白－2,最后通过诱导C2C12细胞产生碱性磷酸酶检测重组人骨形成蛋白－2活性。结果:温度诱导表达重组人骨形成蛋白－2是以包涵体单体的形式存在,经过几步纯化后,得到高纯度的包涵体。重组人骨形成蛋白－2在不同氧化－还原剂比例,和不同小分子化学辅助剂浓度中复性,得到复性的效率也不同。亲和层析纯化后,本实验得到重组人骨形成蛋白－2的生物学活性比商业化的重组人骨形成蛋白－2更高。结论:重组人骨形成蛋白－2属于转化因子－β家族,此复性方法可能应用于此家族的其他成员同时得到成本低、产量高的重组人骨形成蛋白－2,可能为临床应用创造了良好的条件。     

Release of recombinant human bone morphogenetic protein-2 from heterocyclic methacrylate polymer systems.

The release of recombinant human bone morphogenetic protein-2 (rhBMP-2) from three room temperature polymerising methacrylate systems has been studied. These all contained poly(ethyl methacrylate) powder, but the monomer liquids comprised, respectively, tetrahydrofurfuryl methacrylate (THFM), 90/10 THFM/hydroxyethyl methacrylate (HEMA), and 70/30 THFM/ HEMA. In all cases, rhBMP-2 was released, but the addition of 10% HEMA accelerated release (a nine-fold increase in diffusion coefficient); a further increase to 30% HEMA had no additional effect. For most of the release process, a diffusion process operated, although the early stages were not well defined. At the end of the 15 day period, the release, respectively, for the PEM/THFM, PEM:90/10 THFM/HEMA and PEM:70/30 THFM/HEMA systems was 596, 878 and 923 ng (i.e. up to 92% of the rhBMP-2 added).     

Synergism between interleukin-11 and bone morphogenetic protein-2 in the healing of segmental bone defects in a rabbit model.

Recombinant human interleukin-11 (rHuIL-11) and recombinant human bone morphogenetic protein-2 (rHuBMP-2) have been shown to act synergistically in the induction of osteoblast differentiation. To determine whether these two proteins can be used clinically in fracture healing and reconstructive surgery, we investigated whether rHuIL-11 and rHuBMP-2 act synergistically to heal segmental bone defects in a rabbit model. A 1.5-cm segmental defect was created in the right ulnar diaphysis of 20 Japanese white rabbits. Polylactic-co-glycolic acid (PLGA)-coated gelatin sponges (PGS) permeated with rHuBMP-2 (n = 8), rHuIL-11 plus rHuBMP-2 (n = 8), or rHuIL-11 (n = 4) were implanted into the bone defects. Radiographs were scored by two independent observers for bone formation and union rates after 2, 3, 4, and 8 weeks. Bone formation was higher in rabbits implanted with rHuBMP-2 plus rHuIL-11 than in those implanted with rHuBMP-2 alone, reaching statistical significance after 4 weeks. At early time points, the union rate in rabbits implanted with rHuBMP-2 plus rHuIL-11 was higher than in rabbits implanted with rHuBMP-2. At 2, 4, and 8 weeks, new bone volume was significantly higher in rabbits administered rHuIL-11 plus rHuBMP-2 than in those given rHuBMP-2 alone. In contrast, mechanical testing after 8 weeks showed that bone strength in the two groups of rabbits was equivalent. These findings show that rHuIL-11 and rHuBMP-2 act synergistically to accelerate bone formation without affecting bone strength. Treatment with a combination of rHuIL-11 and rHuBMP-2 may thus be of great benefit in fracture healing and for patients undergoing reconstructive surgery.     

The role of recombinant human bone morphogenetic protein-2 in PLGA capsules at an extraskeletal site of the rat.

Bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor-beta (TGF-beta) superfamily and has strong bone-inductive activity in vivo. To examine the role of BMP-2 in an extraskeletal site of rat using a controlled release system of peptides, we encapsulated the recombinant human BMP-2 (rhBMP-2) with poly(DL-lactide-co-glycolide) (PLGA) and implanted the rhBMP-2/PLGA capsules in the subcutaneous area of rats. Upon histochemical examination, it was found that bone-inducing cells having alkaline phosphatase (ALP) activity appeared around the capsules by the suitably released rhBMP-2. In addition, the temporal histological examination showed that direct bone formation without cartilage occurred in the process of this ectopic bone induction. These data indicate that the role of rhBMP-2 in the extraskeletal site of rats is to induce the differentiation of mesenchymal cells into the osteoblasts.Copyright 1999 John Wiley & Sons, Inc.     

腭中缝牵张成骨中骨形成蛋白2的表达

背景：正畸医生常常通过扩大腭中缝矫正上颌骨横向发育不足。骨形成蛋白2可以诱导骨和软骨的形成,促进牵张成骨过程中的骨重建。然而关于骨形成蛋白2在腭中缝牵张成骨中的时间空间表达规律尚不清楚。 目的：观察骨形成蛋白2在大鼠腭中缝牵张成骨过程中的表达规律。 方法：实验选用80只5周龄雄性Wistar大鼠,分为实验组和对照组(包括阴性对照和空白对照)。将初始力值为50 g的腭中缝扩大簧黏接到大鼠两侧上颌牙列上建立大鼠腭中缝牵张模型,牵张1,4,7,14 d后,采用免疫组织化学和实时定量荧光PCR方法分析骨形成蛋白2蛋白和mRNA在各加力时间点的表达。 结果与结论：腭中缝扩张后骨形成蛋白2蛋白表达水平显著增加,且存在时空表达差异,主要定位于腭中缝纤维组织、软骨细胞层、骨细胞和成骨细胞胞浆及其细胞外基质。同时,骨形成蛋白2 mRNA表达也明显上调。提示腭中缝牵张力可刺激骨缝中骨形成蛋白2蛋白和mRNA的合成,在骨缝塑建过程中发挥重要作用。     

Experimental studies on bone induction using low-molecular-weight poly (DL-lactide-co-glycolide) as a carrier for recombinant human bone morphogenetic protein-2

An appropriate carrier acting as a slow delivery vehicle for the BMPs is required for maximal clinical effectiveness of these bone-inductive proteins. The purpose of this study was to evaluate a low-molecular-weight PLGA copolymer as a synthetic, biodegradable carrier for rhBMP-2 implantation in vivo. Two, 10, or 50 microg of recombinant human BMP-2 were mixed with 10 mg of a poly (DL-lactide-co-glycolide) (PLGA) 50:50 copolymer and implanted into the calf muscles of Wistar rats. Soft X-ray analysis and histologic examination indicated that new bone formation occurred at all rhBMP-2-implanted sites within 3 weeks after implantation. Correlation of rhBMP-2 concentration with the amount of bone induction was confirmed by specific alkaline phosphatase activity and calcium content assay. In vitro analysis indicated that 78.5% of the PLGA copolymer was degraded to smaller molecular weight material after 14 days in PBS solution. It is suggested that rhBMP-2 was released in an active form at the implant site during the degradation of the copolymer, resulting in the induction of new bone formation. Thus this low-molecular-weight PLGA copolymer material represents a promising delivery vehicle for BMPs, and possibly other growth factors, around dental and orthopedic implants.