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利用内源性干细胞动员剂和具有成骨诱导性的纳米纤维聚合物支架进行原位骨组织工程。

In Situ Bone Tissue Engineering With an Endogenous Stem Cell Mobilizer and Osteoinductive Nanofibrous Polymeric Scaffolds.

机构信息

Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.

Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea.

出版信息

Biotechnol J. 2017 Dec;12(12). doi: 10.1002/biot.201700062. Epub 2017 Sep 28.

DOI:10.1002/biot.201700062
PMID:28925552
Abstract

Classical bone tissue engineering involves the use of culture-expanded cells and scaffolds to produce tissue constructs for transplantation. Despite promising results, clinical adoption of these constructs has been limited due to various drawbacks, including extensive cell expansion steps, low cell survival rate upon transplantation, and the possibility of immuno-rejection. To bypass the ex vivo cell culture and transplantation process, the regenerative capacity of the host is exploited by mobilizing endogenous stem cells to the site of injury. Systemic injection of substance P (SP) induce mobilization of CD29 CD105 CD45 cells from bone marrow and enhance bone tissue regeneration in a critical-sized calvarial bone defect model. To provide an appropriate environment for endogenous stem cells to survive and differentiate into osteogenic lineage cells, electrospun nanofibrous polycaprolactone (PCL) scaffolds are functionalized with hydroxyapatite (HA) particles via a polydopamine (PDA) coating to create highly osteoinductive PCL-PDA-HA scaffolds that are implanted in defects. The combination of the PCL-PDA-HA scaffold and SP treatment enhance in situ bone tissue formation in defects. Thus, this in situ bone regeneration strategy, which combines recruitment of endogenous stem cells from the bone marrow to defective sites and implantation of a highly biocompatible and osteoinductive cell-free scaffold system, has potential as an effective therapeutic in regenerative medicine.

摘要

经典的骨组织工程学涉及使用培养扩增的细胞和支架来生产用于移植的组织构建体。尽管取得了有希望的结果,但由于各种缺点,包括广泛的细胞扩增步骤、移植后细胞存活率低以及免疫排斥的可能性,这些构建体的临床应用受到限制。为了绕过体外细胞培养和移植过程,利用宿主的再生能力将内源性干细胞动员到损伤部位。全身注射 P 物质 (SP) 可诱导 CD29+CD105+CD45+细胞从骨髓中动员,并增强临界尺寸颅骨骨缺损模型中的骨组织再生。为了提供一个适宜的环境,使内源性干细胞能够存活并分化为成骨谱系细胞,将聚己内酯 (PCL) 纳米纤维支架通过聚多巴胺 (PDA) 涂层功能化羟基磷灰石 (HA) 颗粒,以创建具有高度成骨诱导性的 PCL-PDA-HA 支架,并将其植入缺陷部位。PCL-PDA-HA 支架与 SP 治疗的结合增强了缺陷部位的原位骨组织形成。因此,这种原位骨再生策略结合了从骨髓中招募内源性干细胞到缺陷部位和植入高度生物相容性和成骨诱导性的无细胞支架系统,作为再生医学中的一种有效治疗方法具有潜力。

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