Ch 45 + 48 Delayed union, nonunion, malunion and bone graft Flashcards
- Osteosynthesis
healing of bone through surgical intervention with an implantable device
complex but robust process whereby the event of fracture initiates a cascade of biologic events directed at reestablishing the mechanical function of the bone
method of bone healing, primary or secondary (direct or indirect), is influenced by intrinsic factors of the individual patient and fracture and by extrinsic factors of methods of fracture repair and ancillary treatments
Fracture biology
determined by a number of factors
1.specific bone that is fractured, 2.mechanical environment of the fractured bone
3.biologic health of the fracture and patient
4.whether or not the fracture is treated with surgical intervention
5.manner in which the fracture is surgically stabilized
strain is used to describe the effects of loading on a fracture gap
strain potential; that is, cells or other material occupying the fracture gap would be potentially strained in a manner that is proportional to the change in the size of the gap
effects of change in the fracture gap during loading is that the ability to heal and recover from a fracture can be compromised.
- smaller fracture gaps experience greater strain potential than do larger fracture gaps under similar loading conditions
- formation of various tissue types within the fracture gap is dictated by the degree of interfragmentary strain (motion). In high strain environments, only flexible tissues such as granulation tissue can survive > can withstand almost 100% deformation.
- fibrocartilage is capable of accommodating 10% to 15% deformation.
- Bone tissue can only tolerate 2% deformation. Because survival of osteoblasts and osteocytes requires a low strain environment, fractures with small interfragmentary gaps often result in delayed healing because these small gaps lead to high strain during loading compared to comminuted fractures with larger interfragmentary gaps
- goal of fracture fixation should not be to simply decrease fracture gaps but:
- > (1) eliminate interfragmentary strain through anatomic reconstruction, compression of bone ends with rigid fixation, and absolute stability (eliminate fracture gap and interfragmentary strain)
- > (2) maintain a low strain environment through bridging techniques and implants that allow relative stability
non-union stratagies
- Mechanical strategies aim to realign fracture fragments and attenuate motion at the fracture site to allow healing to occur.
- Biologic strategies aim to preserve or enhance natural healing processes, which then will ultimately reestablish mechanical function.
What are the four tenets of bone healing and regeneration?
Mechanics
Scaffold
Growth factors
Cells
Inadequate Mechanical Environment
geometric and forces
- Geometric configuration centers on alignment of the fracture or reduction of fracture segments. The ultimate goal in fracture repair is that a healed and remodeled bone should take on a form and function of the bone as close as possible to that before injury.
- Too great a gap may overwhelm the healing mechanism.
- function without interference from adjacent soft tissues
Naturally occurring bone healing, as evidenced by development of callus in secondary bone formation, is strongly influenced by motion
- Appropriate motion is an essential part of bone healing because motion triggers both proliferation and differentiation of stem cells.
- - During weight bearing, most forces across the diaphysis are axial, healing tissues are compressed, and, as with a balloon, tension is created on the outside of the fracture callus > tensile strain is the most favorable mechanical environment for bone formation
- Closer to the center of the callus, stem cells are subjected more frequently to compressive forces; therefore, chondrogenesis is favored.
- Shear forces are least tolerated, and even modest amounts can be damaging to cells of a fracture callus. This is true for oblique fractures and axial load and also for transverse fractures in rotational loading
What is the general rule regarding the limits of a viable fracture gap
Should avoid fracture gaps which are approaching the size of the diameter of the bone
In what way is motion as essential part of bone healing?
Motion triggers proliferation and differentiation of stem cells
What is the most favourable mechanical environment for bone formation?
Low to moderate tensile strain and hydrostatic tensile stress
The amount of strain shown to enhance new bone formation in axial load is as high as 36% in some small gap models, and strains of 7% demonstrate far less bone healing
Define stress protection
Inhibition of healing of a fracturedue to too little strain being imparted onto the healing callus
not have adequate mechanical signaling to propagate and differentiate into functional bone
What is generally considered to be adequate strain for fracture healing?
- with regard to simple axial loading and fractures with a few to several millimeters of gap or comminution, strains of 5% to 10% are generally considered adequate
- Limiting strain to less than 1% to 2% should be avoided. Ideally, some strain, or motion, should be seen at low loads, then progressively less at higher loads.
Inadequate Biologic Environment
growth factors and cells
bone morphogenetic proteins > BMP-2 known to be essential
Growth factors> intercellular matrix. Then, Hemorrhage and platelet degranulation
- The principal cell type is the mesenchymal stem cell
- growth factors are active in a very specific temporal orchestration, with the concentration of each waxing and waning in order
- Considerable redundancy
- should concentrate on preserving the local fracture environment and promoting a positive cellular environment»_space; MIO that preserve soft tissue viability and local vascularity
- intrinsic factors (4)
Diaphyseal cortical bone
decreased/compromised vascularity of the periosteum
sparse soft tissue attachments
aged patient
all are negative intrinsic factors for growth factor activity
extrinsic factors
imposed by surgical decisions or techniques.
- Open reduction and internal fixation invade the fracture environment
What is generally considered to be adequate strain for fracture healing?
5-10%
How to mesenchymal stem cells respond to tension and compression?
When under tension, stem cells with differentiate into an osteoblastic lineage
When under compression, stem cells differentiate into a chondroblastic lineage
Where are growth factors which are essential for fracture healing derived from?
Initially derived from the intercellular matrix
Haemorrhage and platelet degranulation further deliver growth factors and cytokines
greatest cellular activity
cellular activity is least
thick periosteum,
metaphyseal bone,
young patients,
high vascularity
modest hydrostatic tension
diaphyseal bone with limited soft tissue attachments,
limited medullary space,
motion that exceeds the mechanical limit of the early fracture callus
hostile environment for stem cell activity is transverse or short oblique fractures of the radius and ulna
Periosteum has low cellular activity. The medullary space and corresponding medullary vascular resources are limited, sometimes severely The requirements for an adequate mechanical environment, limiting the strain to very tight tolerances, are very high because the bone and the fracture gap are very small.
What layer of the periosteum is an important source of mesenchymal stem cells?
Cambium layer
delayed union
prolongation in time for fracture healing.
Retrospectively, a fracture that required a longer period of time to heal than expected was delayed
Mechanical Causes of Delayed Union (2)
- excessive fracture gaps
- motion at the fracture site
- Larger fracture gaps require longer healing times > larger demand for new bone formation (more fertile biologic environment)
- Larger motion results in larger callus, and larger calluses require more time to form.
- if motion at the fracture site exceeds the strain limits > viable nonunion may result.
Biologic Causes of Delayed Union
- intrinsic, extrinsic, or both.
- consequences of inadequate cellular activity.
- high-energy fracturing> periosteum is damaged, compromising source of MSC
- Soft tissue damage > limiting adequate vascular supply.
- growth factors may lie fallow without prerequisite viable cells
- limited temporal period of activity and a lack of responding cells
Treatment of delayed union
preemptive > recognizing adverse healing
minimal biologic activity:
- techniques that will encourage primary bone healing
- encourage a more aggressive cellular response with BMP, graft
fracture gaps > treated with natural or synthetic scaffolds.
Mechanical stiffness of devices should be adequate
postoperative
- serial physical examinations and radiographs
- 3 to 4 weeks, when initial bony activity can be appreciated radiographically
- Pain on palpation/lameness suggest insufficient stability
- If no healing is evident at the early postoperative examination, then the biologic environment should be enhanced
Nonunion
A fracture that fails to progress to osteosynthesis regardless of healing time is a nonunion
failure of an adequate mechanical environment, biologic environment, or both
Viable Nonunions
hypertrophic
- have considerable callus > “elephant’s foot” on either side of the fracture line
- due to excessive motion, or lack of an adequate mechanical environment
- Motion incites a cellular response > exceed the tolerable strain > fibrous tissue rather than bone or cartilage
TX
fibrous tissue at the area of the fracture line should be removed
rigid fixation with dynamic compression
- restore medullary blood flow > drill hole is made from the residual fracture line
- Blaeser 2003: Treatment of biologically inactive nonunions by a limited en bloc ostectomy and compression plate fixation: A review of 17 cases
- Oligotrophic nonunion is a viable nonunion
without radiographic evidence of biologic activity.
- difficult to differentiate from biologically inactive (nonviable) nonunion.
- excessive motion AND lack of cellular activity
- common technical complication = loose implants
TX
removal of loose implants, elimination of interfragmentary motion
reinstallation of a biologically active environment > autogenous bone graft, demineralized bone matrix,
Nonviable Nonunions
biologically inactive so that osteosynthesis cannot occur even with adequate fixation.
A section of the healing fracture area is devoid of viable bone.
4 x nonviable?
- dystrophic > nonviable bone on one or both sides of the fracture. Compromise to the vasculature of the bone has occurred, so there is no living bone tissue on the ends.
- necrotic > implies an infected section of bone, specifically a sequestrum. This bone, being biologically dead, prevents healing.
- defect > gap at the fracture site. This is usually due to a gap too large for normal biologic healing processes to occur; the gap is filled with fibrous tissue rather than living bone
- atrophic > a result of the above; it occurs when dead bone of the fracture area is removed by the host without a healing or restorative process (ends resorb)
nonviable Tx
Requires removal of all nonviable bone and regeneration of new bone
Amputation often chosen due to poor prognosis and expense
Defect non-unions with adequate soft tissue and limb function are surgical candidates
Autogenous cancellous bone grafts (rich source of cells, growth factors, and matrix scaffolds)
rhBMP-2 and rhBMP-7
Rigid fixation (proper anatomic alignment and mechanical function)
ensure no infection
- Alternative tx options: segmental allograft, limb shortening
nonunion tX
Current treatment options are dependent on location and type of non-union.
- segmental bone loss: bone grafting, distraction osteogenesis, and bone transport, low intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field therapy (PEMF).
- Autograft: downfalls of donor site pain and morbidity as well as limited availability as it is impractical to harvest enough bone for repairing a critical size defect.
- allografts have a higher rate of failure (delayed or non-union, infection, or fracture) as well as potential for immunogenicity problems
- BMP-2 has become a prominent treatment option for spinal fusion applications, tibial fractures,
fracture was treated by opening the medullary cavity, performing osteostixis and generous autogenous cancellous bone grafting, and replacing the type II external skeletal fixator with a less stiff type I external skeletal fixator.
Muroi 2020: Application of autologous cortical bone grafts for femoral non-union fractures in two dogs.
limb shortening
Results indicate that dogs having had 10, 15 and 20 percent of their femoral diaphysis removed accommodate well by an increase in the standing angles of the shortened limb.
Malunions
result of failure of mechanical reestablishment of the form and function of the fracture, in which healing still occurs.
- some shortening and translation of a fracture is tolerated
- precision is required > rotational and medial to lateral (frontal) plane alignment of bones.
- imprecision often results in diminished function of the limb.
Treatment of Malunions
Plain radiograph for simple
CT for more complex.
3D/Rapid prototype fabrication
- Intra-op fluoro recommended as normal anatomic markers may not be present
- Locking plates: need not be compressed to bone. Con = no compression
- External skeletal fixators> i.e ring for distraction
alternate non-union tx options
Shock wave therapy
- bone absorb energy > stimulation of bone activity. human beings : efficacy in hypertrophic nonunion but not in atrophic nonunion
Pulsed electromagnetic fields
- treat delayed union and nonunion in human beings. One experimental study in dogs demonstrated a positive effect
Low-Intensity Pulsed Ultrasonography
- noninvasively transferring energy more selectively to bone. the exact mechanism not clear, Current literature on this subject is of low quality and conflicting
Parathyroid hormone for bone regeneration
- PTH may promote bone regeneration and provide an alternative to autograft and BMP use for the treatment of large segmental defects and non-unions
Bone graft and substitutes INDICATIONS:
substantial bone devitalization and/or loss from trauma
resection of a neoplasm,
arthrodesis,
spinal fusion,
nonunion or delayed union
arthroplasty
fragment gap defects during corrective osteotomy
reduced healing potential
- Influences on bone formation include :
molecular signals, cell responses
matrix production,
physical forces, gravity, movement, forces from surrounding tissues (muscle tensile forces)
vascular influences of oxygen tension and delivery of metabolic nutrients
cellular mechanisms behind bone regeneration are not completely understood
-
Mesenchymal stem cell
differentiation into osteoblastic, chondroblastic, adipocytic, tenocytic, or myoblastic lineages
found in adult bone > periosteum, bone marrow, fat - Growth factors
autocrine, paracrine, or endocrine mechanisms
1.TGF-beta > expressed in different cells during bone healing and, therefore, is thought to play roles throughout the entire healing process.
2.FGF > critical role in angiogenesis and proliferation of mesenchymal stem cells.
3.IGF > critical in skeletal development. thought to act locally to encourage cellular proliferation (lengthening and growth)
PDGF > alpha granules of platelets, fracture hematoma aid in initiating fracture healing. Exogenous application of platelet-derived growth factor has been investigated in several animal studies, some suggesting a degree of efficacy however recent 2018 review found final conclusions could not be drawn.
5.Bone morphogenic protein
roles in bone formation and bone healing
Recombinant human BMP-2 studied extensively in dog models to treatment of segmental bone defects, non-union fractures, and spinal fusion
Information on dosage and carriers in these studies has helped define efficacious methods (collagen sponge, calcium phosphate
Osteogenesis
- A graft that directly supplies and supports bone-forming cells is termed osteogenic > strategies nurture an early cellular environment.
- Fresh, autogenous (autogenic or autologous) cancellous bone grafts
- provide a mixture of cells, from fully differentiated osteoblasts lining the cancellous bone to undifferentiated mesenchymal stem cells in the marrow component.
- cancellous bone grafts revascularize more rapidly than fresh cortical
- combined with matrix and signals provided by the cancellous particles
- in vitro studies suggest that greater than 60% of cells that remain at room temperature in normal saline survive up to 3 hours after harvesting
- early as 5 days after implantation, with maximum osteogenesis occurring 8 weeks after transplantation
- osteogenic material is bone marrow
Osteoinduction
Materials that have the capacity to induce bone formation when placed into a site where no bone formation will otherwise occur
- recruit mesenchymal stem cells or their progeny to infiltrate the material of tissues (chemoattraction and migration), and then they induce multipotential cells to multiply and become cells that make up the regenerating bony callus (proliferation and differentiation).
- demineralized bone matrix > decalcifying bone (usually allogeneic)
- TGF-β and BMP-2, -4, and -7, and others
- prostaglandin E2, is also critical, bone formation can be inhibited by chronic nonsteroidal antiinflammatory drug use
Osteoconduction
Material that provides a scaffold for mesenchymal stem cells and their progeny to migrate into, and proliferate
physical materials (biologic or synthetic) of three-dimensional shape offer appropriate framework surface for cells and vascular ingrowth
- may or may not impart load-bearing characteristics
- and may be naturally occurring (e.g., trabecular matrix of cancellous bone) or synthetic (e.g., porous bioceramics).
Osteopromotion
A material or physical impetus that results in enhancement of regenerating bone
- provide different stimulatory signals to bone-regenerating tissues.
- differs from osteogenesis and osteoconduction in that bone formation is enhanced without cells or a scaffold; however, osteopromotive stimuli alone cannot induce bone formation
- platelet-rich plasma,
- hydrogels, and
- biphasic calcium phosphate
Autogenous Cancellous Bone Grafts
number of viable cells minus loss being ex vivo
- The trabeculae are lined with osteoblasts that provide osteogenesis under the influence of local cytokines
- disrupted bone releases cytokines and growth factors from the extracellular matrix; these substances are osteoinductive
- maintains a structural scaffold for new bone (osteoconduction)
- clot contain activated platelets, IGF-1, PDGF, and TGF-β, serving as an osteopromotive function.
- Complications are rare but fracture and premature growth plate closure have been reported. Bone restore by 8 weeks for humerus
- optimal size of the cancellous particles is between 3 and 6 mm
- To obtain the maximum effect > bone defect should be completely filled with graft.
accelerate bone healing by as much as 4 weeks
process post graft implantation
- The initial fracture hematoma > more organized and fibrotic (resorbed 1 to 2 weeks)
- Within minutes to hours> inflammatory response attracts cells, including lymphocytes, plasma cells, and mononuclear cells.
- Revascularization and osteoinduction begin within 5 days
- Necrotic tissue is resorbed > graft is fully vascularized by 20 days
- Woven bone initially deposited on the necrotic trabeculae of the graft and will later be remodeled into lamellar bone
- Osteoclastic (within graft) causes resorption of of necrotic graft after new woven bone has been deposited
- Finally, the new bone is remodeled into cortical bone in response to mechanical stress
graft donar sites (6)
where store?
consequences of drying?
proximal humerus
wing of the ilium. popular > volume of graft and no consequence of iatrogenic fracture
tibia
subtrochanteric region of the femur
condyles of the femur.
rib
- very convenient place to store the graft is in the barrel of a 5- or 10-mL syringe > drying will significantly lower cell viability in as little as 2 hours and cell numbers in as little as 2 to 3 hours
approach to prox. humerus for graft
greater tubercle is palpated and a surgical approach made at the level of the tendon of insertion of the infraspinatus muscle
Allograft-Based Bone Graft Substitutes
- Allogeneic bone has both osteoinductive and osteoconductive properties and capabilities but lacks the osteogenic cells
- Urist’s landmark publication describing bone morphogenetic proteins
- naturally occurring bone morphogenetic proteins, exposed through demineralization, allograft can facilitate induction
- osteoconductive scaffold for vascular ingrowth and for osteoblast
- size is not limited by what can be safely harvested from the patient, nor does allograft bone have the associated morbidity risks involved with autograft
- Histocompatibility issues are ameliorated by most processing methods
- Cortical allografts are used in situations in which structural support is needed, and in which large segments of lost cortical bone need to be replaced inc spinal fusion
- not likely to supply clinically significant amounts of osteoinductive elements. For cortical allografts to provide structural assistance, they must be stabilized by rigid internal fixation and interfragmentary compression
- ## Commercially available allograft bone available in the United States (serologic testing for transmissible diseases)
healing process of allograft
- slow rate of healing (more biologic methods are currently employed)> so more mechanical in limb-sparing
- heal in a different manner to autografts.
- more slowly and greater inflammatory response caused by residual antigenic material.
- bone slowly resorbed by immunologic and/or osteoclastic activity and substituted with host bone—a process known as creeping substitution.
- This process can take months to years depending on the cortical bone mass and the biologic activity at the implantation site.
- complete incorporation of the allograft with host bone matrix may not occur over the life of the patient
- incorporated with the host bone, a process that is enhanced by the addition of autogenous cancellous bone
what is mechanical disadvanatge of allograft?
- biomechanical disadvantage of cortical allograft is the loss of mechanical strength of the graft tissue during the resorption phase of the graft, which will become weaker than the host bone or the unremodeled graft
- Munakata 2018. Clinical efficacy of bone reconstruction surgery with frozen cortical bone allografts for nonunion of radial and ulnar fractures in toy breed dogs
- Bone reconstruction with FCBA is effective in the treatment of radial and ulnar nonunion fractures associated with large bone defects, regardless of the infection status of the surgical site
Demineralized Bone Matrix
no standardized procedure to determine osteoinductivity in allografts
- osteoinductive > inductive cytokines
- ground to specific particle sizes and has been decalcified with the use of acids (typically hydrochloric acid).
- Canine bone 22% to 25% calcium, after demineralization, this is reduced to <3%
- shown to be effective in bone healing
- small mineral content in the milieu favorably influences the formation of bone > shown in study on rats
- ## Removing the calcium exposes acid-resistant BMPs and other GFs > These stimulate mesenchymal stem cells (found by day 10)
demineralised bone use
- can be packed into bone voids, mixed with carriers such as putties, or mixed with autograft, exogenous recombinant bone-specific growth factors
- mixed with allogenic cancellous bone chips provides osteoinductive bone matrix + osteoconductive scaffold
- should be mixed with the patient’s blood or bone marrow to augment the deficiency of progenitor cells in allograft
- used successfully in dogs > studies published in the human and the veterinary literature support the reliable use of allograft bone in bone grafting to promote healing.
- and in titanium cage reconstruction of large segmental defects.
- In a study by Hoffer et al in which autograft was compared with allograft in dogs, demineralized bone matrix was demonstrated to be safe for use in dogs > osteotomy gap and for arthrodesis
how is osetinductions differnt with mineralised nobe matric compared to auto/allograft?
implanted, the process of osteoinduction occurs directly, rather than first going through resorption prior to the formation of new bone (as it does with mineralized autograft or allograft).
2010 review by Innes support its use and further research/applications
- the osteoinductive nature of demineralized bone powder, combined with the osteoconductive properties of cancellous bone, can provide a very effective graft material, especially when mixed with a source of osteogenic progenitor cells.
Cell-Based Strategies for Bone Regeneration
introduce mesenchymal stem cells into the area where new bone is needed (osteogenesis). - expected to:
- proliferate
- produce necessary cytokines,
- differentiate
- invoke a vascular response
- produce matrix and new bone.
- most abundant in the cambium layer of periosteum, bone marrow, and fat. abundant in the young and in areas of cancellous bone
MSC
- Bone marrow–derived mesenchymal stem cells are the most extensively studied.
- Isolation techniques rely on the cells’ property of adhering to certain surfaces.
- will proliferate in specific conditions, with culture expanding the population + osteogenic potential.
- survive cryopreservation and will survive biologic implantation, while maintaining their multilineage potential
- Three strategies (1) culture expanded autologous, (2) culture expanded allogeneic, and (3) selective mesenchymal stem cell retention
goal of cell retention–based bone regeneration
to provide a small but requisite number of mesenchymal stem cells and then to add a carrier matrix with osteoinductive and osteoconductive properties.
- bone marrow aspirate + demineralized cortical fibers + mineralized cancellous chips allomatrix
- In a femoral defect model using dogs, the allomatrix alone resulted in healing in 33% of defects; if bone marrow alone was added, the healing rate was 50%. With selective cell retention techniques, the healing rate was 100%
- allogeneic mesenchymal stem cell–based implants > very similarly to autologous mesenchymal stem cell–based implants
Bone Morphogenetic Proteins
- BMP-2, -4, -7, and -9 are known to have roles in the differentiation of osteoprogenitor cells to osteoblastic cells
- is rhBMP-2 placed on an absorbable collagen sponge and packaged
- several reports have described bone morphogenetic protein use in dogs
- segmental defects of the mandible;
- delayed union or nonunion of the femur, radius, and humerus;
- facilitation of tarsal arthrodesis
- cervical vertebral column fusion
Synthetic Materials for Bone Graft Substitutes
serve as osteoconductive bone graft materials
- Currently a lot of research especially in human dental area, often combing multiple treatments
ceramics
hydrogels
Ceramics
inorganic solid
- surface characteristics biologically compatible and support bone ingrowth > combination of chemistry, sintering, and special physical properties
- interconnective porosity, which allows ingrowth of bone and microvasculature
- Pore sizes of 300 to 500 µm are considered ideal for osteoprogenitor cell infiltration
Calcium Phosphate Ceramics
- modeled after hydroxyapatite, (component of the mineral phase of bone) to duplicate bone
- Bone ingrowth > osteoconductive material
- Calcium phosphates are replaced by osteoclastic resorption, leading to the re-formation of cancellous bone.
- calcium phosphates are available in many forms, from pastes to rigid block
Coralline Bone Graft Substitutes
- ProOsteon is a coralline-derived
- block or granular form.
Tricalcium Phosphate
- calcium-to-phosphate ratio of 1 : 5, compared with hydroxyapatite, which has a ratio of 1.67 : 1.
- ChronOS (Synthes) available in granular wedges and blocks.
- Conduit (DePuy Orthopaedics) supplied as granules.
- Osteoflux > 3D printed synthetic bone graft for oral bone augmentation and bone regeneration
rhBMP6 in autologous blood coagulum with synthetic ceramics for reconstruction of a large humerus segmental gunshot defect in a dog:
(3D)-printed patient-specific polycaprolactone/β-tricalcium phosphate (PCL/β-TCP) scaffold in limb-sparing surgery in a dog with distal radial OSA.
Biphasic Calcium Phosphate
- hydroxyapatite + tricalcium phosphate = greater structural strength and more rapid absorption
Nanocrystalline Calcium Phosphate
- hardens with an endothermic reaction, consists of various forms of calcium phosphate.
- injectable formulations.
Calcium Sulfate
- Calcium sulfates have a rapid absorption rate and, therefore, are not suitable for structural support or for long-term presence as an osteoconductive material.
CHOI 2019: New clinical application of three-dimensional-printed polycaprolactone/β-tricalcium phosphate scaffold as an alternative to allograft bone for limb-sparing surgery in a dog with distal radial osteosarcoma
Synthetic Blocks for Bone Regeneration: A Systematic Review and Meta-Analysis.** 2019**
(3D)-printed patient-specific polycaprolactone/β-tricalcium phosphate (PCL/β-TCP) scaffold in limb-sparing surgery in a dog with distal radial OSA. Significant improvement in limb function and quality of life was noted postoperatively, no complications. The survival time was 190 days.
Synthetic blocks may represent a viable resource in bone regenerative surgery for achieving new bone formation in animal in-vivo trials, clinical studies are required to confirm efficacy
Hydrogels
- three-dimensional polymer networks with aqueous solvent > controlled release of incorporated proteins such as growth factors.
- convenient injectable system
- Biodegradable so implants be completely replaced by bone in order to maximize the mechanical strength of the final repair.
- growth factors: (bFGF), (VEGF), BMPs
- a study using hydrogels as carrier matrixes for in a critical fracture model in dogs reported inhibition of bone formation.
- Further research is required
Xenograft
Jeong 2019: Successful Clinical Application of Cancellous Allografts With Structural Support for Failed Bone Fracture Healing in Dogs
- Bio-oss > bovine derived
- poor osteoinductive capabilities
- also used (rhBMP-2) and Matrigel as osteoinductive and delivery agents.
- In both cases, the fractures healed successfully. Conclusion: C350C can be used as a bone graft material that could replace autografts in cases with failed bone fracture healing. Matrigel is an ECM mixture
Long-Term Assessment of Bone Regeneration in
Nonunion Fractures Treated with Compression-
Resistant Matrix and Recombinant Human Bone
Morphogenetic Protein-2 in Dogs
Castilla 2023
Prospective cohort study with dogs at least 1-year post treatment.
Computed tomography was performed
Six patients met the inclusion criteria. The rhBMP-2 treated bone exhibited
higher density at the periphery and lower density in the centre, similar to the
contralateral limb. All patients were weight bearing on the treated limb and all
fractures were healed
In addition, concerns that BMP treatment does not return bone to normal form and function after remodelling have been reported.
Although excessive or ectopic
bone formation has not been reported in previous veterinary studies using BMP,16,23,33 it is a well-documented side effect of BMP used in spinal fusion procedures
on nonuinion fractures reported in dogs, 60% occur in the radius and ulna and 25% occur in the tibia
Delayed union, non-union and mal-union in 442 dogs
Marshall 2022
Retrospective study
Delayed union occurred in 13.9%
non-union in 4.6%
malunion in 0.7%
Risk factors:
age
comminuted fracture
treatment with bone graft
surgical site infection
major implant failure
prognosis for radial fractures in toy breeds
appears better than historically believed.
3x previous studies nonunion rate: 3.4%- 8.8
radius and ulna most common
non-unions that did eventually heal after revision surgery
took a total median time of 208 days
Human placenta-derived matrix with cancellous autograft
and demineralized bone matrix for large segmental
long-bone defects in two dogs with septic nonunion
Stanley E. Kim 2020
Short case series.
Methods: Both dogs presented for septic nonunion
debridement of nonviable bone resulted in segmental defects of 32% and 20% of the bone length for the antebrachial and humeral fractures
grafting or collapsing the ostectomy site is generally recommended when bone length loss is <20%, and more elaborate options such as bone-transport osteogenesis should be considered when bone length loss is >20%
union was documented at 8 weeks and 6 weeks for the antebrachial and humeral fractures, respectively
Use of three-dimensionally printed β-tricalcium phosphate
synthetic bone graft combined with recombinant human
bone morphogenic protein-2 to treat a severe radial
atrophic nonunion in a Yorkshire terrier
Jordi Franch
1-year-old Yorkshire terrier with a critical-sized left radial defect
after failed internal fixation of a transverse radial fracture
custom-designed synthetic 3D-printed
β-tricalcium phosphate (β-TCP) scaffold. The radius was exposed, and the β-TCP
scaffold was press-fitted in the bone gap underneath the plate. Recombinant human
bone morphogenic protein-2 (RhBMP-2) collagen sponges
18 months after surgery,
there was no evidence of the synthetic graft; instead, complete corticalization
of the affected area was noted.
