PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration.

PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration.
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DOI:
10.1038/gt.2009.117
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发表时间:
2010-01
期刊:
影响因子:
5.1
通讯作者:
--
中科院分区:
医学3区
文献类型:
--
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血小板衍生生长因子- bb (PDGF-BB)刺激愈合受损的慢性伤口如糖尿病溃疡和牙周病变的修复。然而,组织再生的可预测性的局限性部分是由于体内瞬时生长因子的生物利用度。在这里,我们报道了PDGF-B基因的传递刺激了口腔种植体拔牙窝缺陷的修复。在大鼠中制造牙槽嵴缺损,并在钛种植体安装时使用含有编码PDGF-B (5.5×108或5.5×109 pfu/ml)、编码荧光素酶(Ad- luc; 5.5×109 pfu/ml;对照)或重组人PDGF-BB蛋白(rhPDGF-BB, 0.3 mg/ml)的腺病毒(Ad)载体的胶原基质进行治疗。骨修复和骨整合通过背散射扫描电镜、组织形态测量、微计算机断层扫描和生物力学评估来测量。此外,进行了一组局部和系统的安全评估。结果显示,与Ad-Luc相比,Ad-PDGF-B和rhPDGF-BB可加速骨修复,且高剂量Ad-PDGF-B比低剂量Ad-PDGF-B更有效。没有注意到载体结构的显著传播或系统参数的改变。综上所述,Ad-PDGF-B的基因传递在骨组织工程和牙槽骨缺损骨整合方面表现出与体内rhPDGF-BB蛋白传递相当的再生和安全能力。
Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due in part to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5×108 or 5.5×109 pfu/ml), Ad encoding luciferase (Ad-Luc; 5.5×109 pfu/ml; control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg/ml). Bone repair and osseointegration were measured via backscattered SEM, histomorphometry, microcomputed tomography, and biomechanical assessments. Further, a panel of local and systemic safety assessments was performed. Results demonstrated bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared to Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B demonstrates regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable to rhPDGF-BB protein delivery in vivo.
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