Bone and bone graft healing

Bone and bone graft healing

1. BONE AND BONE GRAFT HEALING Presenter: Dr Prajwal K Rao

2. Bone Formation Intramembranous ossification – Direct condensation of mesenchymal stem cells (eg: Flat bones of craniofacial skeleton) Enchondral ossification – MSC form hyaline cartilage template subsequently replaced by bone(eg: Tubular long bones, Vertebral column and Pelvis)

3. Type of Bone Cortical/Compact bone – Dense , Strong accounts for 80% of all bony tissue. Functional unit is Osteon/Haversian System. Cancellous/Trabecular bone – Porous bone comprising 20% of human skeleton.

4. Covering of Bone 2 Layered Periosteum – Outer dense fibrous layer and Inner osteogenic layer which differentiates into osteoblasts when induced. Endosteum - Thin vascular connective tissue lining medullary cavity.

5. OSTEON/HAVERSIAN SYSTEM

6. Chemical Composition Organic ( 30% ) Collagen (type I) 90% Noncollagenous Proteins Inorganic ( 60%) – Calcium Hydroxyapatite Water (10%)

7. Cellular composition Osteoblasts - Metabolically active, Bone forming cells, lining the surface of bone . Osteoclasts - Multinucleated, bone-resorbing cells controlled by hormonal and cellular mechanisms . Osteocytes – Mechanosensory cells that translate physical stress into chemical/electrical signals to stimulate bone remodeling

8. Extracellular matrix Complex scaffolding from which bone derives strength and characteristic architecture. Contains collagenous and noncollagenous phospho and glycoproteins.

9. Bone Repair Primary Bone Repair – Direct cortical healing of two fracture ends without cartilaginous intermediate. Periosteum provides Osteoprogenitor cells and undifferentiated MSCs. Secondary Bone Repair - Un differentiated MSCs proliferate and differentiate into cartilage prior to bone formation at fracture site.

10. Bone healing Healing occurs in three distinct but overlapping stages: Inflammatory Stage Repair Stage Remodelling Stage

11. Inflammatory Stage In the inflammatory stage, a hematoma develops within the fracture site during the first few hours and days. Inflammatory cells (macrophages, monocytes, lymphocytes, and polymorphonuclear cells) and fibroblasts infiltrate the bone under Prostaglandin mediation. This results in the formation of granulation tissue, ingrowth of vascular tissue, and migration of mesenchymal cells.

12. Reparative Stage Callus Formation – Chiefly composed of cartilage and then woven bone, osteoid, fibrous connective tissue and blood vessels. Fracture Callus undergoes both Intramembranous and Enchondral ossification. Eventually, the callus ossifies, forming a bridge of woven bone between the fracture fragments.

13. Remodeling Stage Remodeling of the bone occurs slowly over months to years and is facilitated by mechanical stress placed on the bone. As the fracture site is exposed to an axial loading force, bone is generally laid down where it is needed and resorbed from where it is not needed. Adequate strength is typically achieved in 3 to 6 months

14. Variables influencing bone repair Blood supply - Tubular Long bones have three blood supplies Nutrient artery (inner 2/3 rd cortex and intramedullary ) Periosteal vessels (outer 1/3 rd of cortex) Metaphyseal and Epiphyseal vessels (cancellous bone at end of long bones) Fracture fixation Age

15. Physiology of Bone repair Osteoinduction Osteoconduction Osseointegration Distraction Osteogenesis

16. Osteoinduction Undifferentiated Pluripotent cells are stimulated to become cells within osteoblast lineage. Occurs naturally during skeletogenesis and fracture repair Purified and Recombinant BMP Bioglass – Apatite surface layer is formed when bioactive glass mixed with saline or blood, which incorporates collagen and proteins from surrounding native bone and also stimulates production of osteogenic cytokines from surrounding Osteoprogenitor cells. Adipose tissue, Umbilical cord of neonates and Palatal Periosteum of older infants – Source of MSC

17. Osteoconduction Ability of material to serve as a scaffold on which bone can attach and grow. During Primary bone repair, opposing bone fragments at fracture site mediate osteoconduction and in Secondary bone repair Callus ECM acts as a scaffold. Allografts(Processed human bone), Autogenous bone grafts, Purified collagen, CaP substitutes and Synthetic polymers

18. Osseointegration Stable anchorage between Native bone and Implant without cartilaginous intermediate. Implant must be Bioinert or Bioactive. Bioinert (Commercial Titanium) – Do not stimulate adverse reaction from native tissue. Bioactive – Promotes favorable tissue reaction and chemical bond formation between implant and native tissue.

19. Distraction Osteogenesis Gradual controlled separation of osteotomized bone results in “Tension Stress Effect” leading to angiogenesis and new bone formation 3 main stages: Latency, Activation, Consolidation

20. Latency – between 1 and 7 days, where bone healing is initiated at the bony gap, periosteal integrity is restored and callus formation begins. Activation – Osteogenesis is induced with generation of immature bone. Distraction done by turning of an axial screw at predetermined rate for a certain number of days until target augmentation is achieved Consolidation – Immature to mature bone

21. Variables affecting osteogenesis Device Stability Latency period Gradual distraction Sufficient Consolidation Period Patient factors – Age, Blood supply, Radiation

22. Bone grafts Autografts – From patient Allografts – From another individual Xenografts- From another species Bone substitutes or Implants

23. Indications of Bone grafts Bone gaps in trauma or communiated fractures D elayed or nonunion of fractures Bony defects after benign or malignant lesion resection Reconstruction of functional and contour deficits in craniofacial skeleton Arthrodesis Limb lengthening procedures Spinal fusion

24. Bone graft healing Osteogenesis: Defined as the formation of new bone. This process occurs when viable osteoblasts and osteoblast precursors (stem cells) are transplanted with the bone graft. Osteoblast precursors are found in bone, bone marrow and periosteum, which differentiate into mature osteoblasts under appropriate host conditions.

25. Osteoconduction: Bone graft provides a structural framework on which host cells reconstitute. This scaffold enables the ingrowth of vessels, osteoblasts, and stem cells so that union occurs with the host skeleton. Important structural properties include porosity, pore size, pore connectivity, and surface roughness . Osteoconduction is limited, however, by factors such as size of defect, cellularity of the recipient bed, contact with donor tissue, and host regulation of resorption and remodeling.

26. Osteoinductio n : Recruitment of stem cells from the host bed into the graft site, where they differentiate into osteoblasts. BMP, IGF, PDGF, FGF, EGF, TGF-B and Retinoic acid helps in osteoblast differentiation and proliferation.

27. Bone graft survival Type of graft Quality of transplanted bone and recipient site Mechanical properties of graft Systemic and Local disease Creeping substitution – Process of graft resorption and replacement of necrotic bone by vascular ingrowth and new bone formation.

28. Autografts : Presence of osteoblasts provides direct osteogenesis , presence of growth factors permits osteoinduction, and bone tissue allows osteoconduction. Autogenic bone grafts represent the "gold standard" of bone transplantation. Autografts, both cortical and cancellous, have similar phases of healing and incorporation

29. Histologically, however, there are few differences: 1) Cancellous Autografts are revascularized more rapidly than cortical grafts, 2 ) Cancellous Autografts tend to repair completely with time, whereas cortical autografts remain a mixture of necrotic and viable bone . Cancellous bone grafts indicated in bridge gap less than 5 – 6 cm in nonstress bearing areas. Source: Iliac crest, Cranial diploe, Upper tibial epiphysis and distal radius. Cortical bone grafts is able to bridge defects upto 12 cm in length and provides immediate structural support. Source: Fibula, Rib and Iliac crest

30. Cancellous Autografts: Early Phase: Within first 4 weeks, characterized by inflammation, revascularization, and osteoinduction. Osteocyte precursors and osteocytes that survive transplantation begin producing new bone. Bone marrow necrosis occurs, followed by invasion of host granulation tissue. Revascularization , which may begin as early as 2 days after transplantation, rapidly progresses. Bone morphogenic proteins and other growth factors induce migration of osteoblast precursor cells to the graft. These stem cells differentiate into osteoblasts and new bone forms by the end of the early phase. At 4 weeks, active bone resorption and new bone formation occurs throughout the graft's interior .

31. Late Phase: Proceeds through osteoconduction and eventual graft incorporation. Active graft resorption with new capillary ingrowth continues. Mature osteoblasts line the edges of the dead trabeculae as osteoid is deposited around the necrotic core. Remodeling proceeds and the graft is eventually replaced with live host bone. Skeletal strength is restored as the trabeculae gradually return to normal. The end of the late phase is characterized by replacement of the cancellous autograft with the host skeleton. This occurs approximately 6 months after transplantation and is usually complete by 1 year

32. Cortical Autografts Revascularization is significantly slower, thus prolonging incorporation due to decreased porosity and increased density, which prevents vascular ingrowth. Incorporation of a cortical autograft, in contrast to cancellous autografts, begins with osteoclastic activity rather than osteoblastic until osteoclastic resorption is sufficient to allow vascular invasion of Volkmann and Haversian canals.

33. By the second week, widespread resorption of the cortical graft occurs. This resorption increases during the first 6 months, leading to significant mechanical weakness. Cortical autografts remain a mixture of viable new bone and necrotic bone for a prolonged period.

34. Allografts Primarily acts through osteoconduction. Cancellous allograft may have some osteoinductive potential but it will vary depending on the source and how it was processed and sterilized.

35. Provide a structural framework upon which host osteocytes reconstitute. Fresh and fresh-frozen bone allografts may provoke a greater immune response, freeze-dried and demineralized bone significantly reduces antigenicity. Following allogeneic bone transfer, a nonspecific inflammatory period occurs. Depending on the genetic differences between host and donor, three types of responses are observed: Acceptance (type 1), Partial acceptance (type 2), or Rejection (type 3) Its biologic fate is determined by the aggressiveness of the host's response.

36. Bone graft survival Graft exposure time to air at room temperature should be minimum Graft to be covered in blood soaked sponge with saline gauze. Stored in 10% human albumin and 90% balanced salt solution for longer periods Antibiotic wash to be used with caution Grafts to be kept cold Dead space around graft should be avoided Graft to be placed in previously prepared vascularized bed. Cancellous portion of graft should be placed in contact with cancellous bone in the bed

37. Biology of Conventional Bone grafts Ideal for bone defects less than 6 cm with a well vascularised bed, adequate soft tissue cover and absence of infection. Conventional grafts have substantial problems of fatigue fracture even years after surgical procedure. Successful grafting requires well vascularised bed, adequate immobilization and protection from excessive stress by rigid internal fixation.

38. Biology of Vascularized Bone Grafts Avert reparative phase of nonvascularised grafts and do not depend on recipient bed vascularity. Survival of osteocytes leads to decreased remodeling process during revascularization. Viable bone do not undergo creeping substitution thus significant osteopenia do not occur. Union is more rapid and Bone hypertrophy in response to applied stress may occur with time. ure .

39. Vascularized bone grafts Vascularized bone grafts have superior material properties with greater strength, toughness and elastic modulus . Helps to restore longitudinal growth by inclusion of growth plate . Helps to revascularize adjacent necrotic bone and improves local blood flow in scarred soft tissue beds . Helps to reconstruct composite tissue loss in one procedure with utilization of skin, muscle, tendon and nerves with bone graft .

40. Indications for Vascularised bone grafts Segmental defects >6 -8 cms following Trauma, Oncologic bone loss , Osteomyelitis or Infected Nonunion Biologic Failure – Persistent nonunion, Poor vascularized bone and surrounding tissue. Composite tissue loss – To solve complex tissue defect with a single stage reconstruction Avascular necrosis of bone Osteomyelitis Physeal arrest

41. Reference