Overview of skin, tendon, & bone grafts used in foot & ankle surgery.

1. Simplifying the Science - Advances in Wound, Tendon, and Bone Grafts J. Palmer Branch, DPM Comprehensive Foot and Ankle, LLC www.comprehensivefootandankle.net DrCuboid@aol.com Lilburn, GA (770-921-8800) Cumming, GA (770-886-6833) 1

2. INTRODUCTION 2

3. Overview Many similarities in healing process Skin Tendon Bone Understand the graft concept (allow for ingrowth of new tissue) - Science is secondary. Understand the basic graft healing process and timing of events, then you can determine what to do and when and advance your techniques. 3

4. BASIC CONCEPT The process of skin, soft tissue and bone graft healing is analogous to ivy growing into a lattice or scaffold. Other products and specialized grafts stimulate the healing process itself - Growth factors - BMP - Magnetic bone stimulators 4

5. SKIN HISTOLOGY 1) Epidermis - stratified squamous epithelium epidermal ridges 2) Dermis a) Papillary layer - small blood vessels, lymph & nerves fine collagen & elastic fibers b) Reticular layer - vascular plexus, lymph, nerves & appendages compact collagen fibers & thick elastic fibers 3) Hypodermis (subcutaneous) mainly adipose tissue, sweat glands, blood vessels 5

6. Basics of wound healing 6

7. Growth factors & wound healing 7

8. Bone Structure 8

9. Bone histology - micro Haversian canal and nutrient artery Woven bone with collagen matrix 9

10. Bone trabeculation Trabeculae  10

11. Bone healing - Inflammatory cells - Soft callous formation - Transitions to hard callous - Primary vs. Secondary bone healing – primary facilitated by close contact, stability, compression 11

12. Bone healing Phase 1 (Days 0-4) blood clot then fibrin network forms, TGP PDGF stimulate the chemotaxis and later proliferation of primitive mesenchymal cells Phase 2 (Days 5-9) primitive mesenchymal cells differentiate into chondroblasts and chondrocytes subsequent production of cartilaginous matrix. This matrix is then invaded by capillaries Phase 3 (Days 10-21) Mesenchymal Cell Differentiation Into osteoblasts and osteocytes Type I collagen synthesis (Days 12 through 18) Multinucleated osteoclasts begin the process of bone remodeling. The osteoclasts and osteoblasts replace early bone and remaining calcified cartilage with bone ossicles. By Day 21, bone marrow differentiation occurs 12

13. Bone healing pictures Active osteoblasts laying down compact bone Osteoblasts with multiple nuclei and foamy cytoplasm

14. Tendon Structure 14

15. TENDON – NORMAL VS ABNORMAL A – NORMAL, B – ACUTE RUPTURE, C – TENDINTIS, D- TENDINOSIS 15

16. Tendon healing process Week 1 - Hemostasis, inflammation, growth factor release – Tendon ends retract / phagocytosis of debris - Fibroblastic splint / tendon callous Week 2 – Vascularity of paratenon increases *Preservation of paratenon in surgical repair important. - fibroblasts continue to proliferate Week 3 - Collagen fibers come together and align longitudinally - Classic stage for mobilization, but newer PT/ Achilles rehab studies call for earlier mobilization to reduce adhesions. Week 4 - Inflammation reduces - Improved gliding function - Increased parallel organization and growth of collagen fibers * Maturation at about 8 weeks. * Repaired tendon typically has at best around 80% of original strength. 16

17. GRAFTS Sorry – best phagocytosis shot I had. 17

18. Split-thickness skin grafts 18 Classic problems Donor site morbidity Limited supply Difficulty healing Limited durability

20. Originally released as a cover for periosteum

21. Provides a collagen scaffold for ingrowth of granulation tissueBrigido - Compared single application of GraftJacket to sharp debridement, weekly dressing changes - 85.7% healed with GraftJacket at 12 weeks vs. 28.6% healed at 12 weeks without. Alloderm – similar product / human dermis, often used in burn wounds GammaGraft – Irradiated human dermis. Pegasus (OrthoAdapt) – Recently purchased by Synovis Life Technologies Source is equine pericardium Rejection a possibility 19

22. GraftJacket – healing diagrams

23. GraftJacket – Sample case 21 After debridement Infected wound dehiscence ulcer– 6 weeks s/p I & D, & IV antibiotics GraftJacket applied in OR (Osteoset antibiotic beads and VAC also used.)

24. GraftJacket – Sample case 22 1 week post-op Osteoset absorbable antibiotic beads also noted 2 weeks post - op 8 weeks post-op Wound healed around 16 weeks post - op

25. Business Template 23

26. Topical - Growth Factors Stimulate the healing process Dermagraft – Genzkow showed higher percent at 50% and 100% healed at 8 and 12 weeks vs. control. At 8 weeks 50% of ulcers healed with Dermagraft vs. 8% control 75% vs. 23% fully healed at 12 weeks. Apligraf Future Stem cell-derived products 24

27. Skin substitute / matrix dressings Integra – dermal replacement, bilayered – allows for ingrowth of new skin Dermal layer - Acellular porous lattice - fibers of cross-linked bovine collagen with GAG (glycosaminoglycans) Epidermal layer – synthetic polymer ( polysiloxane) Oasis – Porcine intestinal submucosa, provides extracellular matrix for tissue ingrowth. 25

29. Osteoinduction – Chemically stimulates new bone formation

30. Osteogenesis – Generation of new bone

31. Autograft only – living cells / osteoblasts

33. Bone graft materials - benefits 27

35. Donor Allograft bone– chips, wedges, etc.

36. Xenograft

37. CancelloPure(Wright) – Bovine bone - cancellous wedges – Biocleanse treated, terminally sterilized

38. ProOsteon (InterPore/BioMet -coral)

39. Synthetic / ceramic bone replacements

40. Hardening Putty / Injectable

41. Prodense, MIIG - Wright

42. Norien CRS FastSet Putty (Synthes)

43. Particulate or prefab products

44. Calcium sulfate – Nexa Orthopedics – wedges and plugs

45. Titanium – Biofoam Evans wedges28

46. Bone graft types / examples Osteoinductive substances DBM Grafton (Osteotech), AlloMatrix(Wright), Biomet DBM putty BioMet Platform injectable(Biomet), DBX (Synthes) Bone marrow aspirate harvest system Symphony(DePuy), Magellan (Medtronic) Adult stem cells Trinity Multipotential Cellular Bone Matrix (recent poster at ACFAS) Recombinant human bone morphogenetic protein-2 INFUSE Bone Graft is rhBMP-2 (manufactured BMP) Combination products ProStim - ProDense with DBM Origen DBM Bioactive glass – particulate scaffold / chips with DBM Ignite Power Mix - injectable scaffold of demineralized bone matrix with aspirated red bone marrow. 29

47. Bone Grafts - traditional 30 Cancellous chips Donor site morbidity must be considered (e.g. infections, chronic pain, scarring)

48. Osteoset Absorbable Antibiotic beads {e.g. Osteoset – calcium sulfate} Release antibiotic mixed into the beads into the surgical wound Usually Vancomycin, Tobramycin, and Gentamycin are used. Allows for extremely high local levels of antibiotic into the wound - usually several times over the MIC (minimal inhibitory concentration) for some antibiotic-resistant bacteria. **Polymethymethacrylate removable beads or free-formed spacers may be used for this purpose as well. - must be removed. 31

50. Predictable bone regeneration

51. Stronger than autograft

52. 645% greater compressive strength at 13 weeks vs. autograft *

53. Faster, denser than autograft

54. 170% more new bone vs autograft at 13 weeks*

55. Remodels to normal bone

56. Easy-to use applicator*Urban, et al in canine proximal humerus model, June, 2007 Pro-Dense Injectable Regenerative Graft 32

57. 33

58. PRODENSELAPIDUS 34

59. Prodense Evans Case 35 INTRAOP 9 WEEKS POST-OP

60. Evans - ProDense + Tricortical wedge 36 Evans & T-N fusion Soft lateral calcaneus Tricortical wedge + ProDense injection Rapid ProDense incorporation , slow tricortical wedge incorporation 1 WEEK POST-OP 3 MONTHS POST-OP 6 WEEKS POST-OP

61. Bone stimulators Stimulate the bone healing process - Piezoelectric effect / electronegativity at fracture site - Increase growth factor and receptors - Increase affect calcium flow across membranes - Stimulate endothelial cell and capillary growth and capillary formation. Electromagnetic fields - External - Biomet / EBI, Physio-Stim, DonJoy CMF OL1000 - Internal - Biomet OsteoGen Ultrasound- Exogen (Low intensity pulsed ultrasound) - Mechanical pressure waves transmit through skin and soft tissue results in stimulated growth factors which stimulate bone healing process. 37

62. GraftJacket Cryogenically processed human dermis - Many applications - High tensile strength

63. GRAFTJACKET® Regenerative Tissue Matrix Preserved vascular channels act as “template” for rapid revascularization Typical Freeze-drying Ice crystals damage collagen/elastin Body then recognizes as foreign Initiates inflammatory or immune response Cryogenic Processing Prevents ice crystal formation Structurally intact matrix with: -Collagen -Elastin -Proteoglycans Preserved vascular channels 400x magnified image of non-implanted material demonstrating preserved vascular channel 39

64. Tendon Grafts - examples GraftJacket (standard, MaxForce, MaxForce Extreme) Restore Cuffpatch Biotape XM Acellular porcine dermal matrix OrthAdapt (formerly Pegasus, now Synovis Life Technologies) rejection 40

65. Right Achilles tendon repair. Severe rejection of Pegasus / OrthoAdapt graft with large foreign body granuloma.

66. Growth factors in tendon healing Platelet Derived Growth Factor (PDGF) produced shortly after tendon injury stimulates the production of other growth factors. TGF-beta complex active during the inflammatory and repair phases of tendon healing especially in the in the repair of injured tendons. TGF-beta 1 aids an extra cellular matrix deposition; however, it’s over expression results in tissue fibrosis. TGF-beta 2 functions similarly to TGF-beta 1. TGF-beta 3 has been shown to improve tissue scarring. Highest levels of TGF-beta receptor expression occur at day 14 post injury and decrease until day 56 post injury. Vascular Endothelial Growth Factor (VEGF) stimulates endothelial cell proliferation enhances angiogenesis and increases capillary permeability. VEGF RNA expression is detected at the repair site 7 days post injury with peak levels at 10 days post injury. 42

67. GraftJacket Achilles Tendon Repair standard cannoli wrap technique Improved strength allows for earlier rehab. Can be difficult to close paratenon if thick graft used. 43

68. Tendon transfers / weaves Classic advantages – Improved strength - Earlier rehab to prevent adhesions Classic disadvantage - Loss of donor tendon function / donor site morbidity - Additional surgical site and prolonged OR time. FHL tendon transfer – Achilles repair Pulvertaft weave 44

69. Alternate technique to cannoli wrap 45

70. GraftJacket Strip & Shoelace weave 46 1 - Reapproximate tendon ends 2 - Place inlay strip 3 – Tie in weave strip

71. GraftJacket Strip & Shoelace Weave 47 5 – Weave strip is woven in a shoelace pattern – similar to Pulvertaft technique

72. GraftJacket Strip & Shoelace Weave 48 6 - Closure of the paratenon is facilitated.

73. Creating a GraftJacket weave strip 49

74. GraftJacket Strip & Shoelace Peroneal Tendon Repair 50

75. GraftJacket Strip & Shoelace Peroneal Tendon Repair 51

76. Other tendon grafts / materials Flexiglide - - absorbable mesh graft - limited strength - mostly helpful in adhesion prevention Tenoglide – similar, more friable, difficult to handle

77. Other future graft types Hardening Injectable bone cement –immediate stabilization, limited scaffold effect Stem cells in surgical thread used to repair Achilles tendon. 53

78. Selection of appropriate advanced therapy How can the healing process be best enhanced for the situation? Applying medical expertise and judgment to each situation Medicine is often more an art than a science. Know what each product can do – particular indications and benefits of each device or treatment. 54

79. Summary Understand the basic science. Scaffold effect to reduce the defect. Strength when needed for bone and tendon. Growth factors and other means to speed healing when needed. Use the basic concept to enhance explaining planned procedures to patients. Be able to take your surgical plan to the next level when indicated by not getting hung up on the details of the basic grafting process. 55

80. 56 THANK YOU J. Palmer Branch, DPM – DrCuboid@aol.com Comprehensive Foot & Ankle, LLC www.comprehensivefootandankle.net Lilburn, GA (770-921-8800); Cumming, GA (770-886-6833)