上降文通大学 SHANGHAI JLAO TONG UNIVERSITY 临床医学与材料 (二) 漏 孙康教授 材料科学与工程学院 BWnn 2018-10-13 WA SHANG 1日g6
临床医学与材料 （二） 孙康 教授 材料科学与工程学院 2018-10-13
上游充通大学 SHANGHAI JIAO TONG UNIVERSITY 创伤愈合是指机体遭受外力作 用，器官组织出现离断或缺损 后的愈复过程，包括了各种组 织的再生和肉芽组织增生、瘢 痕形成的复杂组合，表现出各 种修复过程的协同作用。 ● 损伤的程度及组织的再生能力 血液泵 透析液血液 决定修复的方式、愈合的时间 及瘢痕的大小。损伤组织的再 生与修复是机体在生物进化过 半透膜 程中获得的，因此机体的全身 和局部因素，均可影响组织的 液 再生修复。影响再生修复的因 用过的 素包括全身因素及局部因素两 透析液 方面。 血液透析图
创伤愈合是指机体遭受外力作 用，器官组织出现离断或缺损 后的愈复过程，包括了各种组 织的再生和肉芽组织增生、瘢 痕形成的复杂组合，表现出各 种修复过程的协同作用。 损伤的程度及组织的再生能力 决定修复的方式、愈合的时间 及瘢痕的大小。损伤组织的再 生与修复是机体在生物进化过 程中获得的，因此机体的全身 和局部因素，均可影响组织的 再生修复。影响再生修复的因 素包括全身因素及局部因素两 方面
上游充通大学 SHANGHAI JIAO TONG UNIVERSITY Tissue Engineering Tissue damage or organ failure resulting from injury or disease is a major health care problem,and the transplantation of tissues or organs is severely limited.Since 1988,Tissue engineering is a new but rapidly growing field that uses implanted cells,scaffolds,and biologically active molecules to replace or repair injured or diseased tissues and organs. Nervous tissue:Internal communication Brain,spinal cord,and nerves Cell source Novel chemistries Engineering cells iPSCs 器心 Engineering Muscle tissue:Contracts to cause movement Muscles attached to bones (skeletal) Adult stem Muscles of heart(cardiac) Muscles of walls of hollow organs(smooth) cells Growth factors aterials Epithelial tissue:Forms boundaries between different environments,protects,secretes,absorbs,filters Lining of Gl tract organs and other hollow organs Skin surface (epidermis) Genetic tools Progress in tissue engineering Biomechanics CRISPR-Cas9 Connective tissue:Supports,protects,binds other tissues together Bones Decellularized Tendons Fat and other soft padding tissue Self assembly 3D printing organs 日日日且 Engineering tissue architecture Journal of Biomedical Materials Research banner,53(6),2000
3 Tissue Engineering Tissue damage or organ failure resulting from injury or disease is a major health care problem, and the transplantation of tissues or organs is severely limited. Since 1988, Tissue engineering is a new but rapidly growing field that uses implanted cells, scaffolds, and biologically active molecules to replace or repair injured or diseased tissues and organs. Journal of Biomedical Materials Research banner, 53(6),2000
With the development of research,tissue engineering has progressed rapidly in kinds of tissues,such as skin,blood vessels,liver,bone,nerve, e.g. growth cone SCAFFOLD 3 (Peptide WITH growth factors BIOMIMETIC Blood vessel SEQUENCES focal adhesion Factor A BFactor B SCAFFOLD RELEASING GEs biomaterial-based NGC Factor c with intraluminal filaments Platelet-rich Schwann cell regenerating axon PLATELETS ● GENE TRANSFER 00 intraluminal filament 90 Stem Cell Niche (Bone Marrow. Surrounding Tissues...) ACTIVELY PRODUCING CELLS (EPCs) B Biomaterials 35,2014,6143-6156;Neural Regeneration,2015,73-99;Biomedical Engineering,40(5),2012,363-408
With the development of research, tissue engineering has progressed rapidly in kinds of tissues, such as skin, blood vessels, liver, bone, nerve, e.g. Biomaterials 35,2014, 6143-6156;Neural Regeneration, 2015, 73-99;Biomedical Engineering, 40(5), 2012, 363–408
LIMB HAND N individual motor GRIPS for each digit Koy Precision Fully articulated joints Power uscles to make Schematic of pacemaker system
上游充通大学 SHANGHAI JIAO TONG UNIVERSITY 植入物相关感染风险 Device No.inserted in the US per year ”Rate of infection,% Fracture fixation devices 2,000,000 5-10 Dental implants 1,000,000 5-10 Joint prostheses 600,000 1-3 Vascular grafts 450,000 1-5 Cardiac pacemakers 300,000 1-7 Mammary implants 130,000 1-2 Mechanical heart valves 85,000 1-3 Penile implants 15,000 1-3 Heart assist devices 700 25-50
Device No. inserted in the US per year Rate of infection, % Fracture fixation devices 2,000,000 5–10 Dental implants 1,000,000 5–10 Joint prostheses 600,000 1–3 Vascular grafts 450,000 1–5 Cardiac pacemakers 300,000 1–7 Mammary implants 130,000 1–2 Mechanical heart valves 85,000 1–3 Penile implants 15,000 1–3 Heart assist devices 700 25–50 植入物相关感染风险
Bacteria and biofilm The diseases caused by bacteria is a problem in clinical therapy,because of the complicated formation and structure of bacterial biofilm and antibiotic resistance. 5 stages of Biofilm Development Biofilms are the product of a microbial I developmental process.The process is I summarized by five major stages of biofilm I development: I.Initial attachment ll.Irreversible attachment 3 IlI. Maturation I IV.Maturation ll iV.Dispersion Annual Review of Microbiology.2000,54:49-79
Bacteria and biofilm The diseases caused by bacteria is a problem in clinical therapy, because of the complicated formation and structure of bacterial biofilm and antibiotic resistance. Biofilms are the product of a microbial developmental process. The process is summarized by five major stages of biofilm development: I. Initial attachment II. Irreversible attachment III. Maturation I IV. Maturation II V. Dispersion Annual Review of Microbiology. 2000,54: 49–79
The Extracellular polymeric substances (EPS)matrix consists of extracellular DNA (eDNA), polysaccharides,proteins,amyloid fibres and bacteriophages.The EPS matrix functions as a shield to protect the bacterial community or population from predators such as protozoa or lytic phages,as well as from chemical toxins. Phages- Toxins- Protozoa- ◆Signals Food Waste Parental strain eDNA Fattyacid Genotypic and phenotypic variants D Oxygen RsO晚Protein Amyloid fibre Dispersal cell Nitric oxide oocooo Polysaccharide Filamentous phage Dead cell Cold Spring Harb Perspect Biol 2010;2:0000398 Nature Reviews Microbiology,2012(10)
The Extracellular polymeric substances (EPS) matrix consists of extracellular DNA (eDNA), polysaccharides, proteins, amyloid fibres and bacteriophages. The EPS matrix functions as a shield to protect the bacterial community or population from predators such as protozoa or lytic phages, as well as from chemical toxins . Cold Spring Harb Perspect Biol 2010;2:a000398 Nature Reviews Microbiology, 2012(10)
Therapy Strategy 小菌落 细菌解散 细菌的 细胞 基质 瓦解生物膜的4种策略 新型材料让生物膜很难附着 B 降解基质，能够瓦解生物 脂质体(1 liposome）是一些 D 细菌会将一种特殊的脂肪酸 于物体表面。这些材料在纳 膜。这些黏液中的DNA分 中空的小球，能够潜入基质， 作为信号分子发送给其他细 米水平上做成粗糙表面，这 子能够被脱氧核糖核酸酶I 运送抗菌化合物。它们与细 菌，通知它们从生物膜中分 种表面结构可以阻碍细菌黏 (DNAse I)分解。研究人员 菌融合后，会释放出承载的 离出来。研究人员正试图利 附蛋白的附着。 正在能造成耳部感染的生物 杀菌药物。细菌病毒（噬菌 用这种脂肪酸，诱骗细菌分 膜上，测试这种方法。 体)也可以同样的方式进入 离出来。NO也能作为类似 基质中。 I亲水聚合物(PEG) r=·=·一·一·= 两性离子聚合物 儿朗.i ,脂质体/纳米粒子+ Cis-DA 儿Ag杀死接触细菌.一·一 〡抗生素/基质分解酶/抗菌ㄧ Cyclic di-GMP 化合物--- =，=，=，=，-
小菌落 细菌解散 Therapy Strategy 亲水聚合物（PEG） 两性离子聚合物 Ag杀死接触细菌 脱氧核糖核酸酶+抗生素 脂质体/纳米粒子+ 抗生素/基质分解酶/抗菌 化合物··· Cis-DA Cyclic di-GMP NO
上游充通大学 SHANGHAI JIAO TONG UNIVERSITY 人类与感染战斗的历史同我们的 文明一样古老。 过去的几个世纪里，尽管已经 取得很大进步，但毫不夸张地说 每天走进手术室时，对感染的恐惧 存在于每一个外科医生心中。 Javad Parvizi,MD,FRCS 《假体周围感染国际共识2014》
人类与感染战斗的历史同我们的 文明一样古老。 过去的几个世纪里，尽管已经 取得很大进步，但毫不夸张地说， 每天走进手术室时，对感染的恐惧 存在于每一个外科医生心中。 —— Javad Parvizi, MD, FRCS 《假体周围感染国际共识 2014》