Consideration of mechanical factors
Consideration of mechanical factors
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DOI：
10.1111/j.1749-6632.2002.tb03111.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Guldberg, RE
中科院分区：
文献类型：
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作者：
Guldberg, RE
组织工程所需的基本要素包括细胞外基质支架、细胞和组织特异性生物活性因子。这些元件是由宿主提供还是必须以某种组合植入构建体中，关键取决于体内生物化学、血管和机械环境。以骨组织工程为例，对构建体的初始修复反应将根据骨祖细胞的局部可用性、伤口床的血管分布和缺损部位的机械稳定性而显著变化。体内重塑随后将增强、维持或降解在修复期间形成的组织。因此，对组织工程构建体的初始和长期生物学反应受到构建体设计参数和体内环境之间的相互作用的强烈影响。这些相互作用在不同物种、患者和解剖部位之间的可变性代表了组织工程的关键挑战。成功的组织再生必须超越复制形状和结构，以恢复生物和机械功能，并与周围天然组织长期整合。最初，植入的构建体应该是免疫可接受的和生物相容的，并且在许多情况下，促进血管生成和祖细胞的募集。如果满足这些早期反应标准，则可以进行有序的修复序列，最终导致基质合成和沉积。然而，在修复阶段成功的组织形成并不能单独保证长期的功能再生。新形成的修复组织的保留及其与周围组织的整合取决于随后的重塑反应。例如，骨包含骨细胞的复杂细胞通讯网络，并且通过骨吸收破骨细胞和骨形成成骨细胞进行局部重塑，在正常条件下用于维持骨骼结构完整性。然而，在缺乏足够的机械刺激的情况下，骨重建也会迅速去除骨量。这一结果是由一个共同的模型，以测试骨诱导性能，涉及皮下或肌内植入的结构到无胸腺大鼠和其他动物物种。构建体募集局部未分化的细胞，诱导沿着
The basic elements required for tissue engineering include an extracellular matrix scaffold, cells, and tissue-specific bioactive factors. Whether these elements are provided by the host or must be implanted in some combination within a construct depends critically on the in vivo biochemical, vascular, and mechanical environments. Using bone tissue engineering as an example, the initial repair response to a construct will vary substantially according to the local availability of osteoprogenitor cells, the vascularity of the wound bed, and the mechanical stability of the defect site. In vivo remodeling will subsequently reinforce, maintain, or degrade the tissue formed during repair. Thus, the initial and long-term biological responses to tissueengineered constructs are strongly influenced by interactions between construct design parameters and the in vivo environment. The variability of these interactions among different species, patients, and anatomic sites represents a key challenge in tissue engineering.Successful tissue regeneration must go beyond reproducing shape and structure to restore biological and mechanical function and long-term integration with surrounding native tissues. Initially, an implanted construct should be immune-acceptable and biocompatible and, in many cases, promote angiogenesis and the recruitment of progenitor cells. If these early response criteria are met, then an ordered repair sequence culminating in matrix synthesis and deposition may proceed. However, successful tissue formation during the repair phase does not alone guarantee long-term functional regeneration. The retention of newly-formed repair tissue and its integration with surrounding tissues depends on the subsequent remodeling response. For example, bone contains an intricate cellular communication network of osteocytes and is subject to local remodeling by bone-resorbing osteoclasts and bone-forming osteoblasts, serving under normal conditions to maintain skeletal structural integrity. In the absence of adequate mechanical stimuli, however, bone remodeling will also rapidly remove bone mass. This outcome is illustrated by a common model to test for bone-induction properties involving subcutaneous or intramuscular implantation of constructs into athymic rats and other animal species. Constructs that recruit local undifferentiated cells, induce differentiation along an