Dr.T.K.Jeejesh kumar Biology of Distraction Histiogenesis

Distraction osteogenesis Distraction osteogenesis is a unique clinical method for regenerating local bone deficiencies in length, width, or alignment or in bones with intercalary gaps, nonunions, or osteomyelitis.

Introduced by Ilizarov Gradual mechanical distraction of a low- energy osteotomy spontaneously produced potentially unlimited new bone from the local host bone rapidly remodels to normal structure, even in skeletally mature bone.

Aim To understand Biology and the basic science of the Ilizarov method Essential for the practicing limb lengthening surgeon.

 james Aronson  Departments of Orthopedics and Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, Little Rock, Arkansas, U.S.A. Research activities Over a 10-year period, a series of basic research projects was completed in this field to answer three questions:

(i) What growth process occurs within the biological interface that can spontaneously regenerate bone?

(ii) Which are the clinically available variables important to modulate this local biology and to affect outcome?

iii) Do mechanical factors play an intrinsic role in this process of bone?

Materials and methods Sixty-five adult mongrel dogs, divided into subgroups underwent left tibial lengthening to test the effects of variations in technical factors - latency period, - rate and rhythm of distraction, - osteotomy site, - fixator type, - stability.

biopsy and whole bone specimens used 1.decalcified and nondecalcified histology, 2.India ink injection with Spalteholz clearing, 3.back-scattered scanning electron microscopy, 4. Gravimetric (change in mass,volume and desity) 5.chemical analysis( major elements of bone ) 6. biomechanical testing.

noninvasive methods 1.plain radiography, 2.arteriography, 3.technetium scintigraphy, ( blood flow ) 4.computerized axial tomography, ( new bone mineralisation) 5.strain gauge measurements were used in order to correlate findings with the invasive techniques.

different outcomes confirmed by invasive tests, the noninvasive tools were compared in order to develop reliable clinical methods to monitor patients in the clinical setting.

 Studied at various stages after distraction of osteotomy site  Latency period  after 1 week  After 2 week  After 3 week  After 4 week  Consolidation phase  Remodelling phase Histology

 The initial latency period appeared to be no different than routine fracture healing, as might be expected.  Hematoma and inflammatory cell infiltrates filled the gap at the corticotomy site. Histology

 After the start of distraction,  mesenchymal-like cells began to organize a bridge of collagen and immature vascular sinusoids First week

 fibrovascular bridge seemed to organize itself parallel to the direction of distraction  The collagen network became denser and less vascular, almost resembling tendon  vascular channels remained at the proximal and distal edges closely approximated to the cut surfaces of the corticotomy segments.

 central zone of hypovascular fibrous tissue bridges the entire 6 to 7 mm gap  This region has been named the FIZ

Host Bone Zone Fibrous Interzone Host Bone Zone parallel collagen fibres FIZ Fibroblastslike cells DistractionOsteogenesis Week 1 Histology : Zones Vascular sinusoids

collagen is incorporated into each individual bony trabeculum Each microcolumn is surrounded by large vascular sinusoids. Vascular sinusoids collagen fibres Microcolumns

Back-scattered scanning electron microscopy demonstrates mineralized columns of new bone surrounded by loose collagen and vascular spaces. Polarized light microscopy demonstrates uniform incorporation of collagen bundles within each of the two micro- columns pictured, all parallel to the distraction force.

microradiograph

Plain radiography after 1 week

 osteoblast-like cells appeared in clusters adjacent to the vascular sinuses on either side of the FIZ.  Collagen bundles became fused with pink staining matrix-resembling osteoid by routine staining of decalcified specimens. second week of distraction

Host Bone Zone Fibrous Interzone Host Bone Zone PMF PMF inc. in vascularity upto FIZ Osteoblasts like cells Conical Microcolumns Distraction Osteogenesis Week 2

 The osteoblastic cells initially rested on the surface of these primary bone spicules, and eventually became enveloped within, because the spicule gradually enlarged by circumferential apposition of collagen and osteoid  the osteoid began to mineralize. These early bone spicules could be described as the PMF. end of the second week

 The mineralization within the columns was confirmed by von Kossa staining of the nondecalcified specimens Histology specimen at 2 nd week Well organized collagen bundles

Plain radiography at 2 nd week No mineralization

. distraction gap increased, elongation of the new bone spicules. third week

 The tips of the spicules began at a diameter of approximately 7 to 10 microns and rapidly expanded to diameters of up to 150 microns toward each corticotomy surface

 Each microcolumn of new bone was surrounded by large thin-walled sinusoids  The columns were devoid of Haversian canals.

Host Bone Zone F I Z Host Bone Zone PMF formation Increasing length& width of microcolumns FIZ avascular(4-8mm) Vascular sinuses at PMF Distraction Osteogenesis Week 3 PMZ MCF

 No cartilage or osteoclasts were seen.  These regions on either side of the FIZ can be described as the zones of MCF.

New bone formation Non decalcified von kossa stain 4 th week F I Z

Host Bone Zone MCF Host Bone Zone - Bridging of FIZ by microcolumns & vascular channels - Uniform bony tissue Post Distraction Consolidation phase

.cortex & medullary canal.Neovascularity receds.marrow elements in IM spaces Remodelling phase

Decalcified hematoxylin-eosin stained specimen New cortex formed Day 77 post corticotomy- remodeling

Longitudinal Transverse Ultrastructural alignment of new bone

Nerves Muscle Other tissues Other tissues Skin

 1.Stability of apparatus  2.Soft tissue preservation  3.Rate and Rhythm  4. Latency Period  5. Level of osteotomy  6. Physiological loading Variables distraction osteogenesis

1 Mechanical Stability Provide a stable constructProvide a stable construct At least two levels of fixation in each segmentAt least two levels of fixation in each segment No ‘macro’ motion at allNo ‘macro’ motion at all

.If regenerate uniformly poor, .suspect loss of stability. .ADD pins or REVISE fixation Clinical : Mechanical Stability

 1-s2.0-S gr5 2. Soft tissue preservation Classical corticotomy difficult to achieveClassical corticotomy difficult to achieve Preservation of periosteum and minimally traumatic osteotomy desiredPreservation of periosteum and minimally traumatic osteotomy desired

3.Rate of distraction Nerve damage with more than 1 mm/day Early consolidation with 0.5 mm 0.5 mm / day 0.5 mm / day 1.0 mm / day 1.0 mm / day 1.5 mm / day 1.5 mm / day 2.0 mm / day 2.0 mm / day

- once / day - 4 times / day - 60 times / day - auto- distraction 4.Rhythm

- Always 0.25 mm q.i.d. to begin with - Rate limiting factors: Regenerate, Joint stiffness, Neuro-vascular structures Clinical: Rate & Rhythm

- Soft tissue damage - Age - Disease 5.Latency Period lifespan

Metaphyseal Diaphyseal Epiphyseal 6,Level of Distraction

Stimulus for strong skeletal structuring 7.Physiological Loading

 Latency period  after 1 week  After 2 week  After 3 week  After 4 week  Consolidation phase  Remodelling phase summary

Under ideal conditions, a low energy osteotomy preserving blood flow to each apposed surface, distracted at regular, incremental rate of 1mm/day by a stable external fixation system will reliably regenerate a new bone segment of similar macro and micro structure. conclusion

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