modified bone healing

1. FRACTURE UNION AND
RECENT ADVANCES
PRESENTATION BY:
DR .SANDEEP SARAF
ASSISTANT PROFESSOR IN ORTHOPAEDICS
GIMSR

2. • Fracture is defined as a
– break in the continuity of bone
– results in loss of its mechanical stability
– partial destruction of blood supply.
• But following fracture a scar is not formed,
instead a bone has formed
• bone healing the appropriate nomenclature
would be BONE REGENERATION
2
What is Fracture?

3. There are 3 major phases with sub divisions:
• Reactive Phase
– Fracture and inflammatory phase
– Stage of hematoma formation
– Granulation tissue formation.
• Reparative Phase:
– Cartilage Callus formation.
– Lamellar bone deposition.
• Remodeling Phase:
– Remodeling to original bone contour.
4
STAGES OF FRACTURE HEALING

5. • Clinical union
– occurs when progressively increasing stiffness and
strength provided by the mineralization process
makes the fracture site stable and pain free.
• Radiographic union
– present when plain radiographs show bone
trabeculae or cortical bone crossing the fracture
site.
• Radioisotope studies have shown increased
activity in fracture sites long after painless
function has been restored and radiographic
union is present, indicating that the remodeling
process continues for years.

6. • Local factors
• Chemical factors
• Vascular factors
• Systemic factors
• Electromagnetic factors
• Treatment factors
8
INFLUENCING FACTORS

7. A.Type of bone
B. Degree of Trauma
C.Vascular Injury
D. Degree of Immobilization
E. Type of Fractures
F. others: Bone death caused by
radiation
thermal
chemical burns
infection.
9
LOCAL FACTORS

8. 2.GROWTH 3.PERMEABILITY
FACTORS FACTORS
-Proteases
-Polypeptides
-Amines
1.MESSENGER
SUBSTANCES
-Serotonin
-Prostaglandins
-Histamines
-Thromboxane
-Transforming GF
-Fibroblast GF
-Platelet derived GF
-Insulin like GF
-Bone morphogenic
proteins(BMP)
10
2.CHEMICAL FACTORS

9. • MESSENGER SUBSTANCE:
CYTOKINES-
IL-1,4,6,11, macrophage and granulocyte/macrophage
stimulate bone resorption.
IL-1 ,6 synthesis is decreased by estrogen
PROSTAGLANDINS-
Stimulate osteoblastic bone formation and inhibit activity
of isolated osteoclasts.
LEUKOTRINES-
Stimulate osteoblastic bone formation and enhance the
capacity of isolated osteoclasts to form resorption pits.
11

10. GROWTH FACTORS
A.Transforming growth factor(TGF):
-Act on serine/threonine kinase cell wall receptors
- Promotes proliferation and differentiation of osteoblasts,
osteoclasts and chondrocytes
- Stimulates both endochondral and intramembranous
bone formation and collagen type 2 synthesis.
B.Fibroblast growth factors(FGF):
-Increase proliferation of chondrocytes and osteoblasts
-Enhance callus formation & stimulates angiogenesis.
12

11. C.Platelet derived growth
factor(PDGF):
•Stimulates bone cell growth
•Increases type I collagen synthesis by
increasing the number of osteoblasts.
•PDGF-B stimulates bone resorption.
D.Insulin like growth factor(ILGF):
•Stimulates bone collagen & matrix synthesis and
replicates osteoblasts .
•It also inhibits collagen degradation.
13

12. • E.Bone Morphogenic Proteins (BMP):
BMP are Osteoinductive proteins initially isolated from
demineralized bone matrix.
•FUNCTIONS:
–Induce cell differentiation : BMP 3(osteogenin).
–Promote endochondral ossification: BMP 2 & 7.
–Regulate extracellular matrix production :BMP1.
–Increase fusion rates in Spinal fusions (anterior lumbar
interbody fusion): BMP 2
–Non unions: BMP 7 as good as bone grafting .
14

13. • 3.PERMEABILITY FACTORS:
-Protease – Plasmin , Kalikrein, Globulin permeability
factor.
-Polypeptides –leucotaxime, Bradykinin, Kallidin
-Amines – Adrenalin, nor-adrenalin, Histamine.
These factors work in ways that :
– Increase capillary permeability
– Alteration in diffusion mechanism in intracellular
matrix
– Cellular migration
– Proliferation & differentiation
– New blood vessel formation
– Matrix synthesis
– Growth & development.
15

14. 16
3.VASCULAR FACTORS
•A. Metalloproteinases:
–Degrade cartilage and bones to allow invasion
of vessels
•B Angiogenic factors:
-Vascular-endothelial growth factors mediate neo-
angiogenesis & endothelial-cell specific mitogens.
•C. Angiopoietin (І & ІІ)
–Regulate formation of larger vessels and branches.

15. A.Age:
Young patients heal rapidly and have a remarkable ability
to remodel V/S old .
B.Nutrition:
An adequate metabolic stage with sufficient carbohydrates
and protein is necessary.
C.Systemic Diseases:
an immunocompromised state will likely delay healing.
Illnesses like Marfan’s syndrome and Ehlers-Danlos
syndrome cause abnormal musculoskeletal healing.
17
4.SYSTEMIC FACTORS

16. D.HORMONES:
– Estrogen
• Stimulates fracture healing through receptor mediated
mechanism.
– Thyroid hormones
• stimulate osteoclastic bone resorption.
– Glucocorticoids
• increased osteoclastic bone resorption.
– Parathyroid Hormone
• Accelerates callus formation (+osteoprogenitor cells) with
enhanced remodeling & biomechanical properties of healing #
– Growth Hormone
• Increases callus formation and fracture strength
18

17. • In vitro bone deformation produces
piezoelectric currents and streaming
potentials.
• Electromagnetic (EM) devices are based on
Wolff’s Law that bone responds to
mechanical stress: Exogenous EM fields may
simulate mechanical loading and stimulate
bone growth and repair
• TYPES ARE :
– Ultrasound.
– Direct electrical current.
– Pulsed electromagnetic fields (PEMF).
5.ELECTROMAGNETIC FACTORS

18. A.Ultrasound therapy:
• Modulates signal transduction,
increases gene expression
(aggrecan ), increases blood flow,
enhances bone remodeling and
increases callus torsional strength
in animal models.
• Low-intensity ultrasound is
approved by the FDA for stimulating
healing of fresh fractures.

19. • Direct Electrical
current:
– Electric stimulation of
bone has been taught
to be an effective and
non invasive method
for fracture healing
and treating fracture
non union. Studies
shows that electric
field generated helps
in proliferation of bone
cells.

20. 22
C. Pulsed electromagnetic fields (PEMF).
• Approved for the
treatment of non-unions
• Efficacy of bone
stimulation appears to be
frequency dependant
– are most effective (15 to 30 Hz
range)

21. Intertrochanteric hip fractures are
common injuries in the elderly.
Options include extramedullary
and intramedullary implants.
In unstable fracture patterns,
intramedullary devices appear to
have a biomechanical advantage
,lowering the forces imposed on
the implant due to the shorter
lever arm of the fixation.
RECENT ADVANCES

22. PROXIMAL FEMORAL NAIL
Intramedullary nails with two lag
screws were designed to improve
rotational control and bony
purchase within the femoral head,
thus resisting cutout and
subsequent fixation failure.

23. The two lag screw
design led to the
recognition of a new
failure pattern—the
Z-effect

25. TRIGEN
INTERTAN
Low risk of implant failure and non union.
Faster time to union
Eliminates Z effect
Intertrochanteric rotational stability.
Eliminates medial migration
Prevents periprosthetic fracture.

26. PFNA –
2
Indications
Pertrochanteric fractures (31-A1 and
31-A2)
Intertrochanteric fractures (31-A3)
High subtrochanteric fractures (32-
A1)
Contraindications
Low subtrochanteric fractures
Femoral shaft fractures
Isolated or combined medial femoral
neck fractures

27. Large surface and
increasing core diameter
guarantee maximum
compaction and optimal
hold in osteoporotic bone .
Inserting the PFNA-II blade
compacts the cancellous bone
providing additional
anchoring and rotational
stability.
Higher cut outresistance.

28. Elastic Nail
System.
Indications in Pediatrics
•Diaphyseal and certain metaphyseal/-
•Pathological fractures
•Epiphyseal fractures (Salter Harris I and
II), including radial neck,
•Subcapital humerus,
•Metatarsal and metacarpal fractures –
•Complex clavicular fractures
•Indications inAdults
•The osteosynthesis of clavicle
• Forearm and
•Humerus fractures.

29. The elastic flexible nails
are bent and inserted
into the medullary
symmetric Bracing action of two elastic nails having same
modulus of elasticity; which causes three point fixation & gives
rotational, Axial, Translational and Bending Stability

30. EXPERT TIBIAL
NAIL
The Expert Tibial Nail is an intramedullary
implant
Made of titanium alloy (TAN) for improved
mechanical and fatigue resistance
properties Depending on the anatomical
situation, nail lengths between 255 mm
and 465 mm are available in 15 mm steps

31. Multidirectional interlocking
screws ensure that alignment can
be well maintained and stability
preserved in short proximal or
distal tibial segments
The end cap achieves angular
stability between the proximal
oblique screw and the nail.

32. MULTILOC NAILING
SYSTEM:
Modular implant system for the treatment of humeral fracture.
Short and long nail, multiple locking options.
Can be used in both simple & complex fractures.
Nail design:
Straight nail for central insertionpoint.
Improved anchorage in strong subchondral bone.
Perservation of hypovascular supraspinatus foot print.
Multiplanar distal locking reduces implant taggling
Multiloc Screws:
Blunt screw tip to reduce the risk of secondaryperforation
Suture holes to enable reliable attachment of the rotatorcuff.
Counter sunk screw heads to reduce the risk of impingement.
Optional secondary 3.5 mm locking screw (Screw in screw) for improved
fixation in osteporotic bone.
Ascending screw provides medial support.

33. ANGULAR STABLE LOCKING
SYSTEM:
A novel screw & sleeve system is applied using
normal cannulated nails.
Reduces movement at fracture site by 80%
Risk of secondary loss of reduction.
Compatible with cannulated nails.
Free combinations of standard & ASLS screws in
same nail – choice can be made intra op.
Diameter 1: provides purchase in the near cortex
Diameter 2: Expands sleeve, thus providing angular
stability.
Diameter 3: Holds unexpanded sleeve for screw
insertion, provides purchase in for cortex.
(Bioabsorbable sleeve 70:30 poly (L-lactide – l0-D,
L-Lactide)

34. ASLS
Indications :
Metaphyseal fractures with small & less stable fragments.
Osteopenicbone.

35. ACUMED FIBULAR ROD
SYSTEM
ORIF of ankle fractures
Deep wound infection (elderly, diabetics)
Hardware discomfort & irriation.
Often the skin / soft tissue. Envelop may be
compromised.
ACUMED fibular rod system:
Excellent fracture stability
Minimally invasive
Indications:
Lateral mallelor fracture
Unstable ankle fractures with talar subluxation.

36. REAMER IRRIGATOR
ASPIRATION
Novel reaming system
Provides continuous irrigation & suction during reaming.
Was developed to reduce the incidence of fat embolism &
thermal necrosis.
How it works:
Reduces the intramedullary pressure
Reduces potential for fat embolism
Reduces heat generation
Removal of infected tissue.
Indications:
To clear the medullary canal of bone marrow & debris.
To effectively size the medullary canal for the acceptance of an
intramedullary implant.
To harvest finely morselised autogenous bone graft.
To remove infected & necrotic bone & tissue from the medullary
canal in osteomyelitis.

38. NANOTECHNOLOGY IN
INTRAMEDULLAY
NAILING
Treatment of bone infections as in chronic
Osteomyelitis, infected non – union & malunion is a
difficult one & requires more than one surgery.
Eradication of
infection
Curettage/
Sequestrectomy
Antibiotic
PMMAbeads
impregnated
Reconstruction
of bone graft &
soft tissue
Vascularized
fibular graft,
intramedullay
nailing,
Masquelet
techniques
Ilizarov

39. Coating intramedullay nails with nanoparticles containing both
antibiotic & growth factors have the following benefits:
1. Local & precise delivery of microbe susceptible antibiotic with a long
& controllable rate of release for successful eradication of pathogens.
2. Local administration of rh BMP & IGI1 for osteogenesis.
3. Augmentation of the vascular supply of new healthy bone.
4. Maintaining the stability & immobilization of operated bone.

40. The authors suggest the placement of > two
layer of polymer. The superficial layer
contains antibiotics nanoparticles & the
deep layer contains nanoparticles of
growth factors.
These nanoparticles are attached to various
different polymeric material such as poly
(D,L – lactide).

41. Composite verses
metalic
intradmedullary nailing
High rigidity of Ti alloys causes the nail to bear majority of the
load (70-74% in stance phase & 91% in phase).
This leads to stress shielding of the bone
A hybrid composite of carbon fiber/flax / epoxy was used for
Intramedullary & it’s mechanical performance was assessed.
The study showed that the composite material reduces the
negative effects of stress shielding.

42. Conventional manual locking
Trial & error
Maximum no. of fluoroscopic exposures
Novel Surgical navigation concepts for closed Intramedullary nailing
using 4- DOF laser – guiding robot.

43. DRUG ELUTING HEPARINIZED TITANIUM
NAILS
The surface of prsitine Ti – implants is functionalized with
heparin.
Gentamicin sulphate (Gs) and or BMP -2 is then sequentially
immoblized to the heparinized Ti surface.

44. THE TELEMERIZED
NAIL:
Measurement of force & moments acting across the fracture site.
Immediately after fixation – weight is borne by the nail.
As the fracture unites – load is shared by the bone and the nail.
Investigates the implant loading in vivo
Influence of posture & physiotherapy
Load changes due to fracture consolidation

45. INTRAMEDULLARY BONE STENT
Can be made from alloys like SS orshape
memory alloys (e.g. Nitinol)
Inserted into the medullary canal to reduce the
fracture & cause proper alignment
Radial expansion exerts a circumferential stress at
the fracture site, whereas longitudinal contraction
restores the fracture.

46. ADVANTAGES
Has a modulus of elasticity closer tobone
Super elastic property of Nitinol allows it to be deployed in a
compressed state, which can then easily expand & drastically
change its shape & configuration.
Has a titanium based oxide layer that is resistance to corrosion.
The “Spring – like” structure of the stent causes vibration,
which can positively affect the bone density, remodeling,
healing and therefore stimulate rapid bone degeneration.

47. 23
RECENT ADVANCES
Bone graft
Autogenous (iliac crest, prox. tibia, distal femur)
Scaffold for osteoconduction
Has bone matrix proteins  osteoinduction
Has progenitor stem cells  osteogenesis
(free vascular fibular graft for absent radius/ long bone)
Allogenic (from cadaver)
Synthetic (demineralized bone matrix, collagen, ceramics,
cements, polymers- Si, PMMA)
2 emerging products
Tricalcium PO4 composite (VITROSS, CORTOSS)
Hydroxyapatite compound (pro osteon) – marine coral

48. •Bone Marrow Aspirate
•bone marrow contains mesenchymal stem cells and circulating
progenitors
•Mesenchymal stem cells can differentiate into osteoblasts,
chondrocytes, and other connective tissue cells in vitro under
appropriate conditions.
•circulating endothelial progenitors that can contribute to
adult vasculogenesis.
•some of the effects of bone marrow aspirate on fracture healing
could be due to the local application of osteochondrogenic cells
and/or endothelial progenitor cells during bone healing.

49. • Laser Photobiomodulation on Bone
– Laser Phototherapy (LPT) is an effective tool to
stimulate bone.
– results show that the use of IR laser results on
increased bone neo-formation.
– LPT effect depends not only on the total dose, but
also on both irradiation time and mode.
– Energy density and intensity are biologically
independent and accounts for the success and the
failure of the treatment.

50. Percutaneous vertebroplasty:
–
–
–
–
– Vertebroplasty is a minimally invasive, image-guided
therapy used to relieve pain from a vertebral body fracture.
It has been used for osteoporotic or malignant fractures.
Vertebroplasty can increase patient mobility, decrease
narcotic needs, and prevent further vertebral collapse.
Percutaneous vertebroplasty (PVP) usually involves
percutaneous injection of a cement, polymethylmethacrylate
(PMMA), into the vertebral bodies.
Occasionally, PMMA has been placed manually into vertebral
lesions during open surgical operations.
Percut. Inj. (Fibroblast GF-2 + hyaluronon)  callus
formation & mechanical strength

51. 28
• OTHER RECENT ADVANCES:
• GROWTH FACTOR THERAPY
Due to their ability to stimulate proliferation and
differentiation of mesenchymal and osteoprogenitor cells they
have shown great promise for their ability to promote fracture
repair .
• APPLICATION OF PLATELET RICH PLASMA
PRP improves cellular proliferation and chondrogenesis during early
fracture healing and increases the mechanical strength of callus during
late fracture healing
Injecting platelet rich plasma at fracture site helps in fracture healing .
• TISSUE ENGINEERING, STEM CELLS AND GENE
THERAPIES
In past decade tissue culture and stem cells have
been implicated in enhancing fracture healing and articular
cartilage regeneration.