Fracture Healing,Introduction,Pathology&Stages,Factors influencing osteogenesis,differences in healing of fractured bone by conservative&operative management.
Fracture Healing,Introduction,Pathology&Stages,Factors influencing osteogenesis,differences in healing of fractured bone by conservative&operative management.
Bone fractures are a very common orthopedic injury resulting from trauma and sudden loads or stresses applied to bones or a result from bones being weakened by certain diseases. More than 250,000 femur fracture patients are seen per year in the U.S. on average. Bone fractures are either a complete or partial break in a bone and in some cases a simple cast to immobilize the injury site is not enough to completely heal the fracture.
Immobilization from casts may not be enough to completely heal the fracture if a malunion (when both ends of the fractured bone misalign) occurs and/or if a non-union (when the fracture gap is too large and the fractured ends cannot re-attach to one another) occurs. In the case of a malunion or non-union, a possible solution to the problem is by surgically inserting an intramedullary rod into the center canal (diaphysial) region of the injured bone and fixating it into place with screws.
Bone fractures are a very common orthopedic injury resulting from trauma and sudden loads or stresses applied to bones or a result from bones being weakened by certain diseases. More than 250,000 femur fracture patients are seen per year in the U.S. on average. Bone fractures are either a complete or partial break in a bone and in some cases a simple cast to immobilize the injury site is not enough to completely heal the fracture.
Immobilization from casts may not be enough to completely heal the fracture if a malunion (when both ends of the fractured bone misalign) occurs and/or if a non-union (when the fracture gap is too large and the fractured ends cannot re-attach to one another) occurs. In the case of a malunion or non-union, a possible solution to the problem is by surgically inserting an intramedullary rod into the center canal (diaphysial) region of the injured bone and fixating it into place with screws.
Hello guys, bringing to you the concept of golden hour of neonatology. As in trauma, the first hour of neonatal life is most precious and this ppt is an attempt to highlight a few key aspects of this resuscitative strategy in premature infants.
Bone healing dr mohamed ashraf alleppeydrashraf369
biological basis of bone healing.presenting the clinical application of the process and how it fails.presentation by dr mohamed ashraf,professor and head ,govt TD medical college hospital ,alleppey,kerala, india .drashraf369@gmail.com
Bone tissue engineering challenges in oral and maxillofacial surgerySeyed Mohammad Zargar
In this presentation, I talked about maxillofacial deformities, Different Reconstruction methods and at tissue engineering approach.
S.Mohammad Zargar
Biomedical Engineering Student at University of Isfahan, Iran
Ortho: to make straight or right. The use of biologic substances to prompt, stimulate or support a “healing event” within the body.The use of biologic substances to promote healing or reduce pain.The use of platelets and stem cells in treatment and management of musculoskeletal conditions
What is Gene Therapy?
Gene therapy is an experimental technique that uses genes to treat or prevent disease
It focuses on the utilization of the therapeutic delivery of nucleic acids into a patient's cells as a drug to treat disease.
treatment directed to cure genetic diseases by introducing normal genes into patients to overcome the effect of defective genes. These genes deliver individual proteins to specific cells.
Gene therapy in Orthopaedics:
Potential applications of gene therapy as relevant to orthopedics:
Fracture healing
Non-union
Delayed-union
Compound fractures
Grade 3 open fractures.
- Ligament healing
Regeneration of ligaments like patellar tendon (extensor mechanism), ACL or improved fixation and incorporation of grafts
Meniscal tears
- Chondral (articular cartilage) healing and regeneration
- Muscular diseases
Muscular dystrophies
Muscle strain
Utilization of muscle cells as ex vivo delivery vehicles
Osteoarthritis (OA)
Primarily chondral regeneration
Alteration of joint milieu to retard joint degeneration
Rheumatoid arthritis
Altering or remitting the inflammatory process.
Types and Delivery systems of Gene Therapy --
Somatic gene therapy : targets non-reproductive cells
Germ line gene therapy : targets gamete cells – manipulations are passed to progeny
Viral vectors - done by viral transduction
genetically engineered virus permitted to initially infect the cell -- further replication inside cell is prevented
can not infect other cells d/t deficiency in replication
eg - ADV, AAV, HSV, Retrovirus
Non viral vectors - done by transfection (eukaryotic cells made to take up foreign DNA from environment)
- not as effective as viral vectors
- Naked DNA
- DNA -protein complex
- Liposomes (for delivering genes to chondrocytes)
- Gene gun (for muscles and cartilage cells)
Systemic gene therapy
- targets all cells
- injected directly to blood
- treating metastatic diseases
- poor penetration in tissues with decreased blood supply – cartilage and menisci
Local gene therapy
- injected to specific tissue
Direct
- ACL, MCL, Meniscus, Tendon, Ligament
Indirect
- target cell is removed form body – exposed to vector in vitro and reinserted
- spine, articular cartilage, skeletal muscle
Gene delivery systems are categorized as viral-based,non-viral-based and combined hybrid systems -
commonly used viral vectors consist of adenoviruses, retroviruses, and lentiviruses
newer viral vectors that have been developed to improve upon the existing delivery systems like:
- Sendai Virus Vectors (SeV) has been developed as a recombinant viral vector.
Physical methods: Microinjection, electroporation, ultrasound, gene gun, and hydrodynamic applications, etc.
Chemical methods : polymers, liposomes, dendrimers, and cationic lipid systems, etc.
References - Essential Orthopaedics – Principles and practice by Manish Kumar Varshney
Non union of fractures dr mohamed ashraf,HOD orthopaedics,govt TD medical col...drashraf369
presentation about pathophysiology and pathmechanics of delayed and non union of fractures.it shows how to manage different types of bone non union. presentation is by Dr Mohamed ashraf professor and head of orthopaedics,govt TD medical college, alleppey,kerala,india
An overview of management of articular cartilage injuries at various stages. the modalities discussed are PRP, Bone marrow aspirate concentrate, Microfracture, Mosaicplasty and ACI. the pros and cons of each method discussed and compared
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- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
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RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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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. What is a Fracture Healing?
• A complex process that requires the
recruitment of appropriate cells
• the subsequent expression of the
appropriate genes at the right time and
in the right anatomical location.
• A fracture initiates a sequence of
inflammation, repair, and remodeling
that can restore the injured bone to its
original state or near original state.
4. 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.
6. FACTURE UNION
• Union is incomplete repair and the ensheathing
callus is calcified.
• Clinically the fracture site is still a little tender,
the bone moves in one piece, attempted
angulation is painful.
• X-Rays show the fracture line still clearly visible,
with fluffy callus around it.
• Repair is incomplete and it is not safe to subject
the unprotected bone to stress.
7. • 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.
9. 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
11. • 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
12. 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
13. 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
14. • 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
15. • 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
16. 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.
17. 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
18. 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
19. • 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
20. 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.
21. • 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.
22. 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)
23. 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
24. •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.
25. • Use of Serological Bone Formation Markers
– Current serum markers of bone formation activity
include
• bone-specific alkaline phosphatase (ALP)
• procollagen type-I N-terminal propeptide (PINP)
• procollagen type-I C-terminal propeptide (PICP)
• osteocalcin (OC)
– to Monitor Callus Development and Fracture
Healing
– PINP is superior in reflecting bone formation
processes when compared with ALP, PICP, and OC.
PINP can also be characterized as an index of
collagen synthesis, a marker of the early stages of
bone formation, and a marker of callus formation.
26. • 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.
27. 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
28. 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.
29. • Fracture healing is influenced by
many variables including mechanical
stability, electrical environment,
biochemical factors and blood flow
etc…
• Our ability to enhance fracture
healing will increase as we better
understand the interaction between
these variables.
29
SUMMARY
31. • CAMPBELL TEXTBOOK OF ORTHOPAEDICS 11TH EDITION..
• APLEYS PRINCIPLE OF ORTHOPAEDICS
• REVIEW OF ORTHOPAEDICS BY MILLER
• Orthopaedic Knowledge Update 10
• Recent Developments in the Biology of Fracture Repair
• Recent Advances in the Use of Serological Bone Formation
Markers to Monitor Callus Development and Fracture
Healing Marlon O. Coulibaly1, Debra L.
• Recent Advances on the Use of Laser Photobiomodulation
on Bone. A. Pinheiro
• Gene therapy for in vivo bone formation: recent advances
W. LATTANZI1*, E. POLA2*
• The evidence of low-intensity pulsed ultrasound for in
vitro, animal and human fracture healingPilar Martinez de
Albornoz†, Anil Khanna‡,
31
BIBLIOGRAPHY
Editor's Notes
A.Type of bone:
Calcellous (spongy) bone V/S cortical bone.
B. Degree of Trauma:
Extensive soft tissue injury and comminuted #‘s V/S Mild contusions
C.Vascular Injury:
Inadequate blood supply impairs healing. Especially vulnerable areas are the femoral head, talus, and scaphoid bones.
D. Degree of Immobilization:
Immobilized for vascular ingrowth and bone healing to occur.
Repeated disruptions of repair tissue, especially to areas with marginal blood supply or heavy soft tissue damage, will impair healing.
E. Type of Fractures: Intraarticular fractures communicate with synovial fluid, which contains collagenases that retard bone healing V/S Open fractures result in infections V/S
Segmental fractures have disrupted blood supply.
F. others: Bone death caused by radiation, thermal or chemical burns or infection.
D.HORMONES:
Estrogen
Stimulates fracture healing through receptor mediated mechanism.
Thyroid hormones
Thyroxine and triiodothyronine stimulate osteoclastic bone resorption.
Glucocorticoids
Inhibit calcium absorption from the gut causing increased PTH and therefore increased osteoclastic bone resorption.
Parathyroid Hormone
Accelerates callus formation (+osteoprogenitor cells) with enhanced remodeling & biomechanical properties of healing #
Growth Hormone
Mediated through IGF-1 (Somatomedin-C)
Increases callus formation and fracture strength