Bone Regeneration Using Gene-Activated Matrices.
Bone Regeneration Using Gene-Activated Matrices.
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DOI：
10.1208/s12248-016-9982-2
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Salem AK
中科院分区：
文献类型：
--
作者：
D'Mello S;Atluri K;Geary SM;Hong L;Elangovan S;Salem AK
基因转移到骨是一种潜在的治疗策略，用于定向、持续和调节蛋白质表达。用于骨再生的组织工程策略包括将蛋白质、基因（病毒和非病毒介导的递送）和/或细胞递送到骨缺损部位。此外，仿生支架和掺入骨合成代谢剂的支架大大增强了骨修复过程。区域基因治疗具有通过将成骨基因局部递送到骨病变来增强骨缺损愈合和骨再生的潜力，从而减少全身毒性和使用超生理剂量的治疗性蛋白质的需要。通过植入基因激活基质（GAM），可以以刺激骨缺损内的骨生成和骨修复的方式实现原位持续的基因表达和连续的成骨蛋白产生。实质上影响基因疗法的治疗功效的关键参数包括：成骨转基因的选择、非病毒或病毒载体的选择、伤口环境以及离体和体内基因递送策略（例如GAM）的选择。对于基因治疗应用来说，临床有益量的蛋白质以持续的方式在病变内和周围内源性合成是至关重要的。因此，有必要开发可靠和可重复的基因递送方法，并在转化为临床实践之前对其有效性和安全性进行测试。还需要考虑患者的年龄、性别和全身健康状况以及疾病过程的性质等实际因素，以便个性化治疗，并朝着开发临床适用的基因疗法治疗骨缺损的方向取得进展。这篇综述讨论了组织工程的策略，以再生骨与非病毒基因传递系统的具体重点。
Gene delivery to bone is a potential therapeutic strategy for directed, sustained and regulated protein expression. Tissue engineering strategies for bone regeneration include delivery of proteins, genes (viral and non-viral-mediated delivery) and/or cells to the bone defect site. In addition, biomimetic scaffolds and scaffolds incorporating bone anabolic agents greatly enhance the bone repair process. Regional gene therapy has the potential of enhancing bone defect healing and bone regeneration by delivering osteogenic genes locally to the osseous lesions, thereby reducing systemic toxicity and the need for using supraphysiological dosages of therapeutic proteins. By implanting gene-activated matrices (GAMs), sustained gene expression and continuous osteogenic protein production in situ can be achieved in a way that stimulates osteogenesis and bone repair within osseous defects. Critical parameters substantially affecting the therapeutic efficacy of gene therapy include: the choice of osteogenic transgene(s), selection of non-viral or viral vectors, the wound environment, and the selection of ex vivo and in vivo gene delivery strategies, such as GAMs. It is critical for gene therapy applications that clinically beneficial amounts of proteins are synthesized endogenously within and around the lesion in a sustained manner. It is therefore necessary that reliable and reproducible methods of gene delivery be developed and tested for their efficacy and safety before translating into clinical practice. Practical considerations such as the age, gender and systemic health of patients and the nature of the disease process also need to be taken into account in order to personalize the treatments and progress towards developing a clinically applicable gene therapy for healing bone defects. This review discusses tissue engineering strategies to regenerate bone with specific focus on non-viral gene delivery systems.
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影响因子：
3.8
作者：
Do, Anh-Vu;Akkouch, Adil;Green, Brian;Ozbolat, Ibrahim;Debabneh, Amer;Geary, Sean;Salem, Aliasger K.
通讯作者：
Salem, Aliasger K.
影响因子：
82.9
作者：
Bonadio, J;Smiley, E;Goldstein, S
通讯作者：
Goldstein, S
影响因子：
4.9
作者：
Atluri K;Seabold D;Hong L;Elangovan S;Salem AK
通讯作者：
Salem AK
影响因子：
3.7
作者：
Chen H;Liu N;Xu X;Qu X;Lu E
通讯作者：
Lu E
DOI：
10.1016/j.jconrel.2015.09.050
发表时间：
2015-11-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Elangovan S;Khorsand B;Do AV;Hong L;Dewerth A;Kormann M;Ross RD;Sumner DR;Allamargot C;Salem AK
通讯作者：
Salem AK