In vivo session

O18. MRI based perfusion measurements inbone after implantation of biodegradable magnesium rods

Witte F, Bobe K, Meier M

Julius Wolff Institut, Charité - Universitätsmedizin Berlin, Berlin,Germany

Why do we need to know the local perfusion?

CR is depending on flow rate in in vitro systems

In vivo shear stress : 0.68MPa

CR is depending on the local environment

Clearance depends on local blood flow

It is necessary to know the local perfusion to creat “in vivo like”system

Mouse perfusion bone 2.3ml/100g/min

Rabbit bone 19.1 ml/100g/min

RAT femur 8-51 ml/100g/min

   Tibia 7-37 ml/100g/min

Arteral-spin labeling

FAIR(flow-sensitive alternating inversion recovery)

Magnetic Resonance in miedicine 2006, vol.5 108-115

In vivo measurement of perfusion, diffusion and structural changes

Witte European Cells and Materials vol.23, supl.2, 2012

植入鼠骨髓腔10天后血液灌注回到原来水平

Perfusion is depending on species, anatomical location, postoperativetime point

ASL-FAIR MRI sequences are powerful tool to discover: effect ofoperation method, effect of implantation site, postoperative changes in aspecific anatomical site, on local vasculariztion and tissue perfusion

O16. Implant location strongly influencesdegradation and applicability of magnesium alloys for orthopaedic application

Reifenrath J, Roessig C, Wolters L, SeitzJM, Helmecke P, Angrisani N

Small Animal Clinic, Veterinary University of Hannover, Foundation,Hannover, Germany

Bone remodeling process:

Intramedullary pin<intermedullary nail<plate screw system

Results cannot be generally transferred between different applicationarea

O17. The degradation behavior ofMg-3Zn-0.5Zr alloy inan in vitro and in vivo environment

Zhang J, Bi YZ, Chen MF, Huang Y

School of Materials Science and Engineering, Tianjin University ofTechnology, Tianjin, China

Mg-3Zn-0.5Zr, Mg-4Zn-0.5Zr, Mg-5Zn-0.5Zr

O19. In vivo study of iron-basedbiodegradable metals using rat model

Purnama A, Drolet M-C, Couet J, Mantovani D

Institut Universitaire de Cardiologie et de Pnemulogie de Québec,Department of Medicine, Laval University, Canada

316L SSElectroform-Fe A-FeFe-35Mn disc 0.5mm in diameter

1,3 months

Degradation by the presence of fibrious, neovascularization and indicationof inflammatory cells

W4. Coatingtechnologies for corrosion protection of Mg

Prof. Shaokang Guan

School of Materials Science and Engineering, Zhengzhou University,Zhengzhou, China

Biocomposite coating on fluoride coating by PED and TED
inorganic coating for Mg alloystent

Mg-Zn-Y-Nd alloy stent

The grain size was greatly refined to 1 micrometer and nano-particlesuniformly distributed in grains by cyclic extrusion compression.

Density : 1.780 YS: 185MPa UTS 330MPa poisson ratio 0.31, modulus: 42GPa

Metal coverage 3.5mm diameter: 18.62%

Axial recoil rate < 2%

Radial recoil <

TiO2 coating on Mg alloy stens

Inert-good corrosion resitance

Semiconductor antithrombogenic poperties

Prevent hyperplasia (0=30days), increase endothelioid cell adhension anfgrowth (1-2 months)

MgF2+TiO2+Drug,

MgF2 treated with Hf with 24 hours

Nano TiO2 : hydrothermal treatment to obtain anatase TiO2 coating withthe thickness 0.5-1 micrometer

In situ growth of TiO2 on MgF2 , with Hf/NH4F increasing

Drug Rapamycin spraying on top of the above inorganic coating

Hemolysis ratio for bare Mg alloy, nanosheet, nanoparticle, rapamycin47%, 2,7%, 1%, 0.5%

SOP35. Distribution of Fe-based degradablematerials in mice skeletal muscle

Paramitha D, Estuningsih S, Noviana D, UlumMF, Hermawan H

Faculty of Veterinary Medicine, Bogor Agricultural University (IPB),Indonesia

Cr-coated Fe wire 3.0, 1.0mm

SOP36. Degradation of Fe-bioceramiccomposites at two different implantation sites in sheep animal model observedby X-ray radiography

Noviana D, Nasution AK, Ulum MF, Hermawan H

Faculty of Veterinary Medicine, Bogor Agricultural University (IPB),Indonesia

5wt%HA/TCP/BCP

5*2*0.5mm

SOP37. Monitoring of early biodegradation ofFe-bioceramic composites by B-mode ultrasonography imaging in sheep animalmodel

Noviana D, Nasution AK, Ulum MF, Hermawan H

Faculty of Veterinary Medicine, Bogor Agricultural University (IPB),Indonesia

2D-B-mode ultrasonography at day 3, 9 and 14 days of implantation

SOP38. In vitro and in vivo charaterizationof a nitrided iron coronary stent

Zhang DY, Gao RL, Lin WJ, Qin L, Zhang G,Cao P, Qiu H, Wang GQ, Xia Y

R&D Lab, Lifetech Scientific (Shenzhen)Co.,Ltd, China

Plasma nitriding technology

The compound layer should be removed by polishing

Strut : 70+-5micrometer

Degradation 4 years

SOP39. Metal ion level and polymorphonuclearleukocyte cells number as determination factors for early in vivo rejection ofbiodegradable metals

Ulum MF, Paramitha D, Estuningsih S, NovianaD, Hermawan H

Faculty of Veterinary Medicine, Bogor Agricultural University (IPB),Indonesia

Measuring the level of Fe ion in the blood

PLM cell numbers indicate that the composite were not rejected by thesheep

SOP40. In vivo Models for the Evaluation ofDegradable Metallic Biomaterials for Orthopaedic Applications

Dias GJ, Walker J

Department of Anatomy, University of Otago, Dunedin,New Zealand

SOP41. The role of magnesium and associatedalloying elements in human physiology and biology

Qin L

Musculoskeletal Research Laboratory, Department ofOrthopaedics, The Chinese University of Hong Kong, Hong Kong SAR, China

SOP42. Experimental study on stentimplantation for congenital tracheal stenosis in infants and children

Xue BD, Lu ZH, Yuan GY, Xu ZW

Shanghai Children’s Medical Center, Shanghai Jiaotong University(SJTU)School of Medicine, Shanghai, China

Cell culture by rabbit tracheal epithelial cell

气管支架

下午

W6. In vivo models for orthopaedic andcardiovascular applications - selection and implementation

Dr. George Dias

Department of Anatomy, University of Otago, Dunedin, New Zealand

Why in vitro and in vivo evaluation?

To determine biocompatibility, safety and mechanical stability

In vitro testing& limitations

First stage test for acute toxicity & cytocompatibilty

Obtain information: cell proliferation, viability& differentiation

Screening for products qulity& potentially harmful contaminants

Not able to demonstrate tissue response

Cyttotoxicity/compitabilty vary between cell lines and passage number

Overestaimate toxicity, limited to acute cytocompatiiblity

Difficult to mimic/control dynamic properties& cell interactions

In vivo models for orthopedic applications

Inevitable for biomaterial designed gor prthopethic application

Particularly behavior of degradable metals—to access corrosion behaviorand biocompatibility

Interlinked-corrosion products having local

Rodent---can involve subcutaneous, intermuscular or intramuscular locationsin small animals

In vivo testing in soft tissues

Critical size bone defect evaluation

Desirable attributes of an animal models

Standardization & Regulation Update

Prof. Frank Witte

Julius Wolff Institut, Charité - Universitätsmedizin Berlin, Berlin,Germany

Timeline of standard&regulation in biometals

Biometal 2009

FDA March 2012

Biometals 2012, Maratea

FDA ASTM Nov 2012

DIN Nov. 4, 2013 Workshop on Biodegradable Metals, Berlin Germany

US-FDA requests: Report systemic toxicity of Biometals!

i.e., Weight loss of the animal, some signs of the animal organ changes

Solutions for a better in vitro – in vivo correlation

ISO/TC 150/SC 2/WG 7 Cardiovascular absorbable implants

Challenges with current ISO testing

Cytotoxicity testing according to ISO 10993-5

72h incubation for extract tests

Wxtraction volume based on sample surface or weight

Animal test according to ISO 10993-6

Implantation in dynamic environment for X week

Which in vivo time period is your in vitro experimental resembling?

基于GAP in results，可以反过来想：先在动物体内植入一段时间，取出然后称重变化，再来做体外实验找到对应这个重量变化的对应体外实验时间点

ED min, Mininium Extract dilution, ED cyto,  Ed max, maximum Extract dilution

Safety factor= ED cyto/Ed max

Closing Remarks

Prof. Diego Mantovani

Lab. for Biomaterials & Bioengineering (CRC-I), Dept.Min-Met-Materials Engineering & University Hospital Research

晚餐的BBQ，有烤鱼和烤虾吃