In vivo constructs after maturation in mice： Whitish with glistening； Firm in consistency.
体内、外构建的差异（关节软骨）
Articular cartilage constructs in vitro
Articular cartilage constructs in vivo
promoting human keratinocytes (epidermal cells) to multiply and to differentiate to replicate the architecture of the epidermis.
Apligraf without : • Melanocytes; • Macrophages; • Lymphocytes; • Blood vessels; • Hair follicles; • Sweat glands.
• Developing mathematical models for cell growth and tissue formation；
• Devising experimental techniques to determine model parameters such as oxygen consumption rate and effective diffusivity in the tissue；
生物力学检测
样品制作、保存； 实验设计：选择指标、样本量、数据处
组织工程研究内容
组织工程研究过程
干细胞 工程
细胞 改造
细胞接种 应力与生长
生物学及 力学检测
种子细胞 支架材料
构建模式 体内 体外
工程化 组织
工程化组 织的保存
材料设计 加工检测
生物反应器、力学 植入技术 诱导与信号的转导 修复技术
植入技术 修复技术
Simple culture techniques
SEM
体外构建的耳软骨
Newly formed in vitro auricular cartilage construct
Ear cartilage construct with the chondrocytes
静态、动态构建的差异（软骨）
动态构建: 有软骨陷窝; 有软骨基质分泌.
静态构建: 无软骨陷窝; 无软骨基质分泌.
Monitoring of the cell viability, functionality and tissue formation；
Developing continuous sampling and analytical technologies using micro- or nano-probes；
工程化组织的理解
Special culture
Engineered tissue
The engineered tissue， or construct， usually consists of three-dimensional scaffolds and living cells with the desired structure and functionality.
体内构建
本位：功能位置； 皮下：浅表位置； 肌内：深度位置； 骨内：骨膜内。
体内构建的皮肤
Reconstructed human skin on the dorsal of the nude mice at 4 weeks after transplantation
体内构建气管软骨
皮下：浅表位置
Devising and developing new types of bioreactors, particularly addressing mass transfer and mechanical signaling.
简单
复杂
Байду номын сангаас低维
多维
On-line monitoring in engineered tissue
体内、外构建的差异（皮肤）
Apligraf consists of living cells and structural proteins: Lower dermal layer combines type 1
collagen and fibroblasts (dermal cells), which produce additional matrix proteins; Upper epidermal layer is formed by
If specific signals are not properly received or processed, then the cells dedifferentiate (i.e., become nonspecific cell types), become disorganized, and eventually die.
Purposes of tissue engineering
Medical application purpose
Research purpose
To develop biological substitutes for implantation into the body ;
To foster tissue regeneration and remodeling;
静态:细胞或支架相对静止； 动态:细胞或支架相对运动； 存在的问题：
环境条件、营养条件(生物反应器) 。
生物反应器系统
静态:常规二氧化碳培养箱； 动态:旋转培养系统、拉伸/压
缩/扭转培养系统、电磁培养 系统、声学/光学培养系统。
Perfusion of Culture System
Improve mass transport throughout the scaffold by perfusing media through cell seeded scaffolds and stimulate those cells via flowinduced shear stress.
Enabling efficient control of the tissue culture bioreactor and optimization of the construct design and bio-processing operation.
Cryopreservation of engineered tissues
Dynamic microenvironment
Cell colonies need external cues or signals to grow into functional 3D tissues. Cells are constantly bombarded with mechanical, electrical, structural, and chemical cues that signal the cells about what they should be doing.
工程化组织的构建 (Construct of engineered-tissues)
四川大学华西临床医学院 干细胞与组织工程研究室
秦廷武
Dec. 22, 2006
The concept of tissue engineering
The term ‘tissue engineering’ was officially coined at a National Science Foundation workshop in 1988 to mean the application of principles and methods of engineering and life sciences toward fundamental understanding of structure-function relationships in normal and pathological mammalian tissues and the development of biological substitutes to restore, maintain or improve tissue function.
• The models can be applied both in vivo and in vitro.
工程化组织的构建方法
体外构建
（工程化椎间盘）
体内构建
（工程化耳软骨）
体外构建
在体外模拟体内细胞的动态微环境，包括 生物化学、生物物理环境。提供组织特有的生 物的、化学的和物理的刺激，产生相应的传导 信号。并提供细胞营养及代谢通路。
﹡ 细胞―材料
细胞 材料
？ 有机结合体
Bioreactors for Tissue Culture
Bioreactors are purpose-designed tissue culture system；
Providing the desired biochemical and mechanical environment for cell adhesion, proliferation, differentiation and function；
Preservation and storage of live engineered tissues, or bio-constructs, would be one of the major obstacles for the commercialization.
Mathematical modeling in tissue engineering