Principios biológicos en ondas de choque

Transcription

1 Principios biológicos en ondas de choque W. Schaden Trauma Center Meidling, Vienna, Austria Ludwig Boltzmann Institute for experimental and clinical Traumatology Austrian Cluster for Tissue Regeneration

2 For almost 40 years shockwaves are used successfully in urology practically without side effects. Just the mechanical properties of shockwaves were of interest (PRESSURE). For use in all other medical disciplines the biological effects are most important. The absence of dangerous long term effects (malignant degeneration of treated soft tissues, etc.) is the only important message.

3 Effects on Bone Tissue In control X-rays performed one year after disintegration of ureter and bladder concrements, Haupt (1986, Bochum) observed a thickening of the iliac bone where the shockwaves passed through. kidney swollen ureter iliac crest where the SW travels through stone in ureter bladder

4 Effects on Bone Tissue In the beginning we focused on the mechanical forces.

5 Hypothesis: ESWT Mechanical Model Provocation of micro lesions in the tissue initiates and stimulates tissue repair/regeneration processes.

6 Histological findings 3 weeks after high energy shockwave application: highly active osteocytes/osteoblasts formation of new bony tissue necrotic osteocytes (empty vacuoles) cortical swelling

7 ESWT Mechanical Model Today we know that this hypothesis was completely wrong..

8 ESWT Mechanical Model First doubts on this mechanical model came up when Schaden et al. (2001) could show, that less number of pulses (= less total amount of energy) is more efficient in the treatment of non-unions. Maier et al. (2002, Munich) proved most efficient osteostimulation in rat femura at energy levels without any mechanical destruction.

9 Influence Number of Impulses Pulses Number Healed Failure < (72%) 70 (28%) > 3000 < (79%) 47 (21%) > < (65%) 14 (35%) > < (62%) 14 (38%) > (70%) 28 (30%) total (73%) 173 (27%) Numbers are shown for long bones and scaphoid Schaden et al., 2001, Clin Orthop

10 Osteointegrity depending on energy M. Mayer (2002) Fracture in trabecular bone Fracture in cortical bone 6 5 * 6 5 * Animal [n] Animal [n] ,35 0,5 0,9 1,2 EFD [mj/mm 2 ] * = p<0,05 vs. ESWT ,35 0,5 0,9 1,2 EFD [mj/mm 2 ] * = p<0,05 vs. ESWT

11 Case Report 58 years old, male, TKR June 96, supracondylar fract. March 2000 => double plate, cemented KR; May 2000 dislocation => re-plating; July 2000 dislocation => long stem revision TKR, cerclage; October 2000 fracture of the stem, persistent non-union October 2000: ESWT + plaster cast (8weeks)

12 Case Report 6 months after ESWT

13 65 year old, male, fall over steps, HIV-positive, diabetic I open tibia fracture same day UTN

14 65 year old, male, fall over steps, HIV-positive, diabetic 3 months after trauma => ESWT 3 months after ESWT 3 years after ESWT

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18 ESWT for Non-Unions F 1 F 2

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20 epigastric art.

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24 11.7 cm cm 2

25 Results Effect of Shockwave Treatment on Area of Necrosis in Rat Skin Flaps Area of Necrosis (sqcm) Treatment Group Shockwave Control p=0.0006

26 Laxity, Elastic Deformation, Stiffness, Elasticity: comparable to contralateral side

27 From Mechanical Model to Bioresponse Lower amounts of pulses more effective (Schaden) Osteogenesis without mechanical destruction (Maier) Hypothesis: SW treatment causes biological responses without damaging / destroying tissue

28 Biological Response of Shock Wave in Tendon Materials and Methods: 50 New Zealand white rabbits, 12 months old, body weight ranging from 2.5 to 3.5 Kg were used in this study. The right limbs (study side) received 500 impulses of shock wave treatment at 14 KV (equivalent to 0.18 mj/mm 2 ) to the Achilles tendon near the insertion of the heel bone. The left limbs (control side) received sham treatment. Wang (Taiwan)

29 Biological Response of Shock Waves in Tendon Materials and Methods: Biopsies of the Achilles tendon-bone unit were performed in both the study and control limbs in 0, 1, 4, 8 and 12 weeks with 10 rabbits at each time period. The neo-vessels were examined microscopically with H-E stain. Tendon Bone (Neo-vessel) (10 X) (H-E stain) (40 X) Wang (Taiwan)

30 Results of Neo-Vessels # Neo-Vessels Control Shockwave P-value -1 (N=50) (N=50) 0-week (N = 10) Mean±SD 22 ± 3 24 ± week (N = 10) Mean±SD 24 ± 4 26 ± P-value week (N = 10) Mean±SD 22 ± 5 42 ± P-value week (N = 10) Mean±SD 24 ± 5 40 ± P-value week (N = 10) Mean±SD 25 ± 6 42 ± P-value P-value -1 : Comparison of control with shock wave therapy; P-value -2 :Comparison of 0-week with 1-, 4-, 8- and 12- week. Mann-Whitney test. (40x). Wang (Taiwan)

31 Results of enos Expression Microscopic Features of enos Expression: Bone Tendon (Control) Bone Positive enos cell number 450 Control Shock wave Tendon (Shock Wave) Weeks after shock wave therapy ESWT promotes the expression of enos signal transduction. The effects of shock waves appear to be time-dependent. Wang (Taiwan)

32 Results of VEGF Expression Microscopic Features of VEGF Expression: (Control) (Shock Wave) Positive VEGF vessel number Control Shock Wave Weeks after shock wave therapy ESWT promotes VEGF induction for angiogenesis. The effects of shock waves appear to be time-dependent. Wang (Taiwan)

33 Results of PCNA Expression Microscopic Features Bone of PCNA Expression: Tendon (Bone) (Control) Bone Positive PCNA cell number Control Shock Wave Tendon (Shock Wave) Weeks after shock wave therapy ESWT promotes cell proliferation at the tendon-bone junction. The effects of shock waves appears to be time-dependent. Wang (Taiwan)

34 Biological Responses Vasculogenesis Control SW LCx occlusion in pigs 4 weeks Nishida et al., 2004, Circulation

35 Biological Responses Inflammation Control ESWT Murine dorsal full-thickness burn Davis et al., 2009, Int Wound J

36 Biological Responses Stem Cells Regeneration by increased cell differentiation Differentiation of bone-marrow mesenchymal cells by the induction of osteogenic growth factors such as transforming growth factor beta 1 (TGF- 1) Extracorporeal shock wave promotes growth and differentiation of bone-marrow stromal cells towards osteoprogenitors associated with induction of TGF- 1 F. S. Wang et al. J Bone Joint Surg; 2002;84-B:

37 Biological Responses Stem Cells Recruitment of i.v. administered EPC to ischemic adductor muscle is significantly enhanced after SW pre-conditioning Red EPC Green vwf White laminin Blue - nuclei Aicher et al., 2006, Circulation

38 Biological Responses Stem Cells

39 Biological Effects of Shock Waves o o o o o o o o o Permeability change of cell membrane Stimulation of mitochondria, ATP release Dilution of substance p Reduction of non-myelinited nerve fibers Anti-inflammatory effect Angio- and vasculogenesis Promotion of NO (nitric oxide) Promotion of growth factors (VEGF, BMP s, OP s, etc.) Mobilization, Migration and (differentiation) of stem

40 Is it possible to communicate with biological tissue?

41 Lorenz Böhler ( )

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45 . communication with muscle???

46 . communication with kidney beans??? kidney beans control group kidney beans shockwave group Grant De Poyster Drew 2A estem High School March 20, 2011

47 . communication with nerve cells??? orange dots: active mitochondria in nerve cells before ESWT.immediately after ESWT

48 ...communication with skin and other tissues??? before ESWT after ESWT D. Jankovic, U. Dreisilker, Interdisziplinäre Zeitschrift für Gefäßkrankheiten, 5, 2/2009, 39-43

49 communication with biological systems is possible via mechanotransduction

50 Ingber, 2006, FASEB Journal Receptors in Organs and Cells

51 Mechanotransduction Mechanotransduction is a mechanism to transform mechanical stimuli into biochemical/electrical responses: hear feel / proprioception regulation of blood pressure It influences dimension, form and mobility of cells Cells can actively change their shape reacting to mechanical influences Masahiro Sokabe

52 Direct mechanotransduction Jaalouk, Nature Rev 2009

53 Indirect mechanotransduction Wang, Tytell, Ingber Nature Rev 2009

54 .challenges with a new language without dictionary

55 Message to be taken home: shockwaves do not damage tissue shockwaves stimulate biological regeneration via mechanotransduction

56 April 15 th 18 th, 2015

57 Titelmasterformat durch Klicken bearbeiten First ESWT-application on open heart