BONE HEALNG AND REPAIR

1. BONE HEALNG AND REPAIR SEMINAR BY ARIFA HASSAN 2ND MDS DEPT OF PROSTHODONTICS

2. CONTENTS • INTRODUCTION • HISTORY • BIOLOGY OF BONE  • STRUCTURE • COMPOSITION • HISTOLOGY • BONE HEALING  TYPES OF BONE HEALING STAGES OF BONE HEALING BONE HEALING AT IMPLANT SITE • BONE GRAFT • GUIDED BONE REGENERATION  • COMPLICATIONS OF BONE HEALING • FACTORS INFLUENCING THE BONE HEALING • RECENT ADVANCES • CONCLUSION • SUMMARY

3. INTRODUCTION • Bone repair after fracture is a special process where sequential cellular and molecular events take place to generate new bone, rather than a fibrous scar, like other connective tissues. • The precise series of ordered events required to produce new bone are modulated by systemic and local factors, and disruption of these orderly events may cause healing problems. • Thus, a clear understanding of the sequence of events and their regulation is needed to decide when and how an intervention is required to promote healing and to avoid complications.

4. Fracture is defined as a break in the continuity of bone. Fracture results in loss of its mechanical stability and also partial destruction of blood supply. • Healing means to make whole or sound again, to cure, leaving a scar behind. But following fracture a scar is not formed, instead a bone has formed a new at the original fracture site. So rather than bone healing the appropriate nomenclature would beBONE REGENERATION

5. HISTORY • History of fracture and its knowledge dates back to Egyptian mummies of 2700 B.C • In 17th century Albrecht Haller, observed invading capillary buds in fracture callus and thought that blood vessels are responsible for callus formation. • John Hunter, a pupil of Haller, described the morphologic sequence of fracture healing.

6. In 1873, Kolliker observed the role of multinucleated giant cells, osteoclast to be responsible for bone resorption. • In1939, Gluksman suggested pressure and shearing stresses are possible stimuli for fracture healing. • In 1961, Tonna and Cronkie demonstrated the role of local mesenchymal cells in fracture repair.

7. WHAT IS BONE ? • Bone is essentially a highly vascular, living, constantly changing mineralized connective tissue which makes up body’s skeleton. functions are: - Bone provides protection for the vital organs of the body( eg: heart and brain) - The hematopoietic bone marrow is protected by the surrounding bony tissue. - Storage of calcium and phosphate. BONE biology,harvaesting ,grafting for ental implants rationale and cliical applications by Arun K. Garg

8. MACROSCOPY Living bone is white, with either dense texture like ivory or honeycombed by large cavites. • Spongy bone (cancellous) : is composed of a lattice or network of branching bone spicules or trabeculae. The spaces between the bone spicules contain bone marrow. • Compact bone (cortical / outer): appears as a mass of bony tissue lacking spaces visible to the unaided eye. Orban’s oral histology and embryology by 12thediton by GS Kumar

10. MICROSCOPY • Woven (Immature bone):Characterized by random arrangement of cells and collagen ,associated with periods of rapid bone formation, such as in initial stage of fracture healing. • Lamellar bone (Mature bone) : Characterized by an orderly cellular distribution and properly oriented collagen fibres . This constitutes the organised bone in both cortical and cancellous bone Orban’s oral histology and embryology by 12thediton by GS Kumar

12. PERIOSTEUM Is a membrane that lines the outer surface of all bones except at the joints of long bones. • Is made up of : • Outer FIBROUS layer : made up of white connective and elastic tissue. • Inner CAMBIUM layer : which has a looser composition, is more vascular and contains cells with osteogenic potency. Molecular biology of bone remodelling. Nadia Rucci. Clinical Cases in Mineral and Bone Metabolism 2008; 5(1): 49-56

15. FUNCTIONS OF PERIOSTEUM: • Anchors tendons and ligaments to bone. • Acts as a limiting membrane. • Participates in growth (appositional) and repair through the activities of the osteoprogenitor cells • Periosteum helps in fracture healing by forming periosteal callus. •  Allows passage of blood vessels, lymphatics and nerves into and out of the bone. Molecular biology of bone remodelling. Nadia Rucci. Clinical Cases in Mineral and Bone Metabolism 2008; 5(1): 49-56

16. BONE COMPOSITION BONE biology,harvaesting ,grafting for ental implants rationale and cliical applications by Arun K. Garg • CELLS • OSTEO PROGENITOR CELLS • OSTEOBLASTS • OSTEOCLASTS • OSTEOCYTES • BONE LINING CELLS • EXTRACELLULAR MATRIX • ORGANIC MATERIAL 25% • INORGANIC MATERIAL 60% • WATER 15%

18. BONE CELLS • 1.OSTEO PROGENITOR CELLS

20. 2.OSTEOBLASTS • Are bone forming cells, which are cuboidal to pyrimidal in shape , these cells are located where new bone is forming, eg:in the periosteum. • Cytoplasm contains ribonucleoproteins which are responsible for synthesis of protein matrix • During osteogenesis , osteoblastsecreate growth factors(GF)---Transforming GF,Bonemorphogenic proteins(BMP),Platelet derived GF,Insulin like GF. • Which are stored in the bone matrix Orban’s oral histology and embryology by 12thediton by GS Kumar

21. Osteoblasts contain the enzyme alkaline phosphatase used to calcify the osseous matrix.(deposition of calcium and phopherous) • Arrive in 3-5 days with early angeogenesis at wound site • As they become entrapped in the forming bone they differentiate into osteocytes

22. The synthesis type 1 collagen, osteocalcin (bone Gla protein) and osteonectin

24. 3.OSTEOCLASTS • Osteoclasts are bone resorbing cells and their activity is controlled by PTH(In the bone PTH causes demineralization or decalcification by inducing the pyrophosphatase enzyme in the osteoclasts) • Giant, multinuclear cells . • They are found on the surfaces of osseous tissue usually in shallow depressions called Howship’s lacunae. Orban’s oral histology and embryology by 12thediton by GS Kumar

25. The osteoclast is characterized by acid phosphatase within its cytoplasmic vesicles and vacuoles, which distinguishes it from other giant cells and macrophages • Under E.M. the cell surface facing the osseous matrix shows numerous cytoplasmic projections and microvilli described as a ruffled border.

26. OSTEOCLASTS RUFFLED BORDER MICROSCOPIC PICTURE ELECTRON MICROSCOPY

27. This Villisecreateproteolytic enzymes that digest or dessolve the organic matrix • Via phagocytosis ,osteoclast absorb minute bone particles & crystels and dissolve them,and release the products into the blood stream BONE biology,harvaesting ,grafting for ental implants rationale and cliical applications by Arun K. Garg

28. 4.OSTEOCYTES • Basically, an osteoblast that has been enclosed within the bony matrix in a space called the lacuna. • In developing bone, the cytoplasmic processes from one osteocyte make contact with the processes (canaliculi) from adjoining osteocytes. In mature bone, the processes are withdrawn almost completely. • In mature bone the empty canaliculi remain as passage ways for the diffusion of nutrients and wastes between bone and blood. Orban’s oral histology and embryology by 12thediton by GS Kumar

31. 5.BONE LINING CELLS • These are similar to osteocyte and they are the retired osteoblat cells • Are flattened epithelium in adult skeleton found on resting surfaces. • Plays active role in differentiation of progenitor cells • Controls osteoclasts, mineral hemostasis and may secrete collagenase. • Lines – endosteal surface of marrow cavity - periosteal surface Orban’s oral histology and embryology by 12thediton by GS Kumar

33. Bone healing • Bone healing ,or fracture healing,is a proliferative physiological process in which the body facilitates the repair of a bone • In classic histologic terms, fracture healing has been divided into two broad phases: • Primary healing • Secondary healing Peterson’s principles of oral and maxillofacial surgery 3rd edition ,volume 1 by Michael Miloro, G.F. Ghali, Peter Larsen ,Peter Waite

34. TYPES OF BONE HEALING • PRIMARY or direct healing by internal remodelling • Bone is directly formed from one fragment to another • Healing occurs without callus formation as in compression plating • It occurs only with absolute stability and is a biological  process of osteonal bone remodeling . Peterson’s principles of oral and maxillofacial surgery 3rd edition ,volume 1 by Michael Miloro, G.F. Ghali, Peter Larsen ,Peter Waite

35. In fact, this method is employed only after rigid surgical fixation, or in case with a partial crack in the bone, a so-called "unicortical" fracture, where the remaining bone holds everything rigid. • In brief: Primary bone healing is lead by the formation of a so-called cutting cone (consisting of osteoclasts at the front of the cone to remove bone and trailing osteoblasts to lay down new bone) across the gaps to form a secondary osteon

37. Primary healing involves a direct attempt by the cortex to reestablish itself once it has become interrupted • Bone on one side of the cortex must unite with bone on the other side of the cortex to reestablish mechanical continuity Principles of bone healing Iain H. KalfasS, M.D., F.A.C.S. Neurosurg Focus 10 (4):Article 1, 2001

38. Two types • CONTACT HEALING: When there is direct contact between the cortical bone ends, lamellar bone forms directly across the fracture line , parallel to long axis of the bone, by direct extension of osteons. • GAP HEALING: Osteoblasts differentiate and start depositing osteoids on the exposed surfaces of fragment ends, mostly without a preceding osteoclasticresorption which is later converted into the lamellar bone

40. Principles of bone healing Iain H. KalfasS, M.D., F.A.C.S. Neurosurg Focus 10 (4):Article 1, 2001 SECONDARY: It is usual type, consisting of formation of callus either of cartilaginous or fibrous. This callus is later replaced by lamellar bone. It is comparable to healing of soft tissue by filling of gaps with vascular granulation tissue.

41. Secondary healing involves responses in the periosteum and external soft tissues with the subsequent formation of a callus • The majority of fractures heal by secondary fracture healing

42. STAGES OF FRACTURE HEALING • There are 3 major phases with sub divisions: • A.Reactive Phase: • i. Fracture and inflammatory phase. • ii. Stage of hematoma formation. • iii. Granulation tissue formation. • B.Reparative Phase: • iv. Cartilage Callus formation. • v. Lamellar bone deposition. • C.Remodeling Phase: • vi. Remodeling to original bone contour.

43. A.REACTIVE PHASE Principles of bone healing Iain H. KalfasS, M.D., F.A.C.S. Neurosurg Focus 10 (4):Article 1, 2001 I .Fracture & inflammatory phase : After fracture the first change seen by light and electron microscopy is the presence of blood cells within the tissues which are adjacent to the injury site. Soon after fracture, the blood vessels constrict, stopping any further bleeding.

45. 20 years of guided bone regeneration in implant dentistry 2nd edition by Daniel Buser, ChristerDahlin , Robert K.Schenk

46. . ii. Stage of Hematoma formation: Within a few hours after fracture, the extravascular blood cells form a blood clot, known as a hematoma. All of the cells within the blood clot degenerate and die. The fracture hematoma immobilizes &splints the fracture. The fracture haematoma provides a fibrin scaffold that facilitates migration of repair cells.

47. iii. Granulation Tissue Formation Within this same area the fibroblasts survive and replicate. They form a loose aggregate of cells, interspersed with small blood vessels, known as granulation tissuewhich grows forward, outside and inside the bone to bridge the fracture. They are stimulated by vasoactive mediators like serotonin and histamine.

48. B. REPARATIVE PHASE .THE BIOLOGY OF FRACTURE HEALING IN LONG BONES B. McKIBBIN THE JOURNAL OF BONF. AND JOINT SURGERY, VOL. 60-B.No. 2. MAY 1978 iv. Cartilage Callus formation : Days after the # the periosteal cells proximal to the fracture gap and fibroblasts develop into chondroblasts which form hyaline cartilage. The periosteal cells distal to the fracture gap develop into osteoblasts which form woven bone. These 2 tissues unite with their counterparts and culminate into new mass of heterogenous tissue called Fracture Callusrestoring some of its original strength.

50. v. Lamellar bone deposition: Or consolidation ..where hyaline cartilage and woven bone is replaced by lamellar bone. This process is called Endochondral ossification. At this point, the mineralized matrix is penetrated by channels, each containing a microvesseland numerous osteoblasts.  This new lamellar bone is in the form of trabecular bonewhich restores bone’s original strength.