Bone grafts and Guided bone

regeneration(GBR)
Dr Priyank Rai
JR-1, Unit of Prosthodontics & Crown and Bridge & implantology

17th October, 2022

30 years of guided bone regeneration / edited by Daniel Buser, Page-2, ISBN: 9780867158038
Bone Grafts and bone substitutes
sin Zhao;Ruijia Yang;Paul R. Cooper;Zohaib Khurshid;Amin Shavandi;Jithendra Ratnayake; (2021). Bone Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments . Molecules, (), –. doi:10.3390/molecules261030
 Functions of Bone augmentation materials

Provide mechanical support to prevent membrane collapse.

Stabilize the blood clot.
Allow ingrowth of blood vessels.
Act as an osteoconductive scaffold for bone ingrowth.
Maybe osteoinductive.
May contain bone cells.
Become integrated into or replaced by bone.
Protect the augmented volume from resorption.
 Biologic properties of bone filler materials

Osteoconductive- materials with a matrix to serve as a scaffold

and act as a template for bone deposition.
Osteoinductive-contain proteins (BMPs) that stimulate and
support the proliferation and differentiation of uncommitted
stem cells to become osteoblasts.
Osteogenic-autogenous bone contains bone cells (bone-lining
cells, osteoblasts, osteoblast uncommitted stem cells, and/or
osteocytes. Can support bone formation directly or indirectly.

30 years of guided bone regeneration / edited by Daniel Buser, Page-67, ISBN: 9780867158038
 Autogenous bone graft

Preferred material due to its osteoconductive, osteoinductive and

osteogenic properties.
The availability of osteogenic cells and growth factors depends largely on
:
• patient’s age
• presence of systemic diseases
• location of the donor site
GFs are released either passively or during the resorption of the
autografts.
Dependent upon the absolute surface area of the graft.
i.e, blocks of cancellous graft and particulate graft demonstrate the faster release of GFs.
Cancellous bone grafts exhibit a faster rate of revascularization (maximum 0.2–0.4 mm ⁄ day) than
cortical bone grafts (0.15– 0.30 mm ⁄ day)
Autogenous particulate grafts

Autogenous bone from bone collectors.

Autogenous bone from bone mills.
Autogenous bone collected with a piezoelectric
technique.
Autogenous bone from bone scrapers.
 Limitations of autogenous grafts

Harvesting may require an additional surgical intervention.

unpredictable resorption of up to 60% of cortico- cancellous block grafts
increased operative time, costs, intraoperative blood loss, pain, and recovery time.
associated with an increased risk of donor site morbidity .
the supply of autogenous bone for grafting may be limited.
 Allografts

obtained from either a compatible living donor or from cadaveric bone sources.
preparation in three primary forms—fresh frozen(FFB), or freeze-dried(FDBA or DFDBA)
FDBA and DFDBA contain osteoinductive molecules such as BMPs.
allografts decelerated new bone formation in comparison with autografts (positive control) and
coagulum (negative control)
DFDBA showed osteoconductive properties, but the osteoinductive potential could not be demonstrated.

Buser D, Hoffmann B, Bernard JP, Lussi A, Mettler D, Schenk RK. Evaluation of filling materials in membrane-protected bone defects. A comparative histomorphometric study in the mandible of
miniature pigs. Clin Oral Implants Res 1998;9:137–150
 available in various forms, from whole bone segments, cortico-cancellous, and cortical pieces to chips,
wedges, pegs, powder, and DBM.
DFDBA with transport vehicles (glycerol, starch, hyaluronic acid, collagen, and saline)
improved handling and adaptability due to the hardening of the mixture and its components.
slow release of BMPs increases the osteoinductive potential in FDBA.
Limitations of risk of infectious disease transmission(HIV, HBV, HCV
high-temperature treatment resulted in less bone formation and lower osteoconductivity than chemical
treatment

Rusin Zhao;Ruijia Yang;Paul R. Cooper;Zohaib Khurshid;Amin Shavandi;Jithendra Ratnayake; (2021). Bone Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments . Molecules, (), –.
doi:10.3390/molecules26103007
 Xenografts
act solely as an osteoconductive scaffold.
Bovine bone is treated with a stepwise annealing process followed by chemical
treatment with NaOH.
considered the standard of care for sinus augmentation procedures due to their
superior stability and low immunogenicity.
a healing period of 8 months is recommended when used as the only grafting
material.
As deproteinized bovine bone is free of proteins, osteoclastic resorption can
probably not occur. deproteinized bovine bone
 Chitosans

derived from the exoskeletons of crustaceans composed of glucosamine and N-acetylglucosamine.

stimulate bone regeneration by providing a structural scaffold that
• supports osteoblastic activity,
• the formation of mineralized bone matrix and
• inducing differentiation of MSCs into osteoblasts in various in vitro environments
• a hydrophilic surface that promotes cell adhesion and proliferation.

Silk fibroin

commonly used as a bone scaffold in sponge, fibres., film and hydrogel forms
indicated for use as a GBR membrane:
• following tooth extraction, cyst/tumor excision
• deficient alveolar bone for implant placement
 Phytogenetic materials

Gusuibu(Drynaria fortunei)-
• promotes bone calcification and remodelling processes due to
• osteoinductive properties & increased alkaline phosphatase activity
Corals- the osteoconductive potential of coral-derived bone substitutes is less than that of other bone substitute
materials
Algae-In contrast to coralline HAs, phycogenic fluorapatite undergoes slow resorption by enzymatic and cellular
degradation
 Alloplastic materials(Osteobiologics)

• calcium phosphates (CaPs)-HAs and TCPs, bioactive glasses, and polymers

• HA is considered to be osteoconductive and non-resorbable
• TCP also demonstrates osteoconductive properties but resorbs rapidly
• limits its use in bone augmentation procedures performed for esthetic purposes.
• combinations of HA and TCP—biphasic calcium phosphates (BCPs) formulations
• varying the HA: TCP ratio to modulate the substitution rate and bioactivity of these biomaterials
• Recent research To develop BCPs, which are osteoinductive are being conducted.
• Bioglasses exhibit bone bonding as a result of the surface reactive silica, calcium, and phosphate groups
• The optimal particle size of 300 microns for bone formation
• silicon dioxide (SiO ), sodium oxide (Na O), calcium oxide (CaO) and phosphorus pentoxide (P O )
2 2 2 5

• addition of potassium oxide (K O), magnesium oxide (MgO) and boric oxide (B O)
2 2

• The desirable properties of bioglass include:

good biocompatibility, osteoconductivity, antimicrobial activity and a porous structure promoting
vascularization
• bioglass can be used in a mixture with autogenous bone at the floor of the maxillary sinus,
 Biofunctionalization
Coating of bone substitutes with biologics like GFs
DBBM can absorb a lot of the patient’s own proteins and other macromolecules from the environment
due to its high macro- and nanoporosity so it appears suitable for biofunctionalization.
 Comparisons of
Different bone substitutes

• 4 weeks- More bone formed in autografts

• 12 and 24 weeks- highest bone formed in TCP
• Highest degradation rate for TCP
• Volumetric stability in other 3 groups

Buser D, Hoffmann B, Bernard JP, Lussi A, Mettler D, Schenk RK. Evaluation of filling materials in membrane-protected bone defects. A comparative histomorphometric study in the mandible of miniature pigs. Clin
Oral Implants Res 1998;9:137–150.
110.Jensen SS, Bornstein MM, Dard M, Bosshardt DD, Buser D. Comparative study
of biphasic calcium phosphates with different HA/TCP ratios in mandibular bone
defects. A long- term histomorphometric study in minipigs. J Biomed Mater Res B
Appl Biomater 2009;90:171–181.
 Different options to promote and support bone formation

Osteoinduction by growth factors.

Osteoconduction by autogenous bone grafts and
substitutes.
Transfer of stem cells that differentiate into osteoblasts.
Distraction Osteogenesis/Distraction Histogenesis.
GBR using barrier membranes.
Factors that may lead to failure of bone regeneration

Failure of the vascular supply.

Mechanical instability- inadequate immobilization.
Oversized defects.
Competing tissues of high proliferative activity.
Principles of GBR
Bone is a relatively slow-growing tissue.
Fibroblasts and epithelial cells can occupy the
available space to build up soft CT.
A barrier membrane, if lasts long enough can keep
these undesirable cells from the defect area.
It creates a secluded space for bone regeneration in
an undisturbed manner.

Membrane and defect compartments in GBR

Omar O, Elgali I, Dahlin C, Thomsen P. Barrier membranes: More than the barrier effect?. J Clin Periodontol. 2019;46(Suppl. 21):103–123. https://doi. org/10.1111/jcpe.13068
 Requirements of a GBR membrane
Biocompatibility- exhibit an appropriate tissue response.
Occlusive property- Prevent soft tissue invasion and
bacterial infiltration.
Space-making capacity- maintenance of defect space.
Attachment to or integration with the surrounding tissues.
Manageability- clinically manaegable

Dahlin, C. (2010). Optimal implant placement in the esthetic zone by the use of Guided Bone Regeneration. In L. Andersson, K.-E. Kahnberg, & M. A. Pogrel (Eds.), Oral and maxillofacial surgery (pp. 357–366). Chicago,
IL: John Wiley & Sons Ltd..
 Classification of GBR membranes
Membrane groups/Materials Main advantages Main disadvantages

Synthetic polymers • Inert and stable polymer in the Non-resorbable

Polytetrafluoroethylene biological system

Aliphatic polyesters • Bioresorbability Lack of rigidity

(e.g. PLA, PGA. and PCL) • Good processability and manageability and stability
• Drug-encapsulating ability

Natural polymers
Collagen and extracellular • Bioresorbability
matrices derived from bovine, porcine and • Low immunogenicity Lack of rigidity
human tissues • Drug-encapsulating ability and stability
Chitosan • Incorporation of biological components
Alginate • Hemostatic

Metals
High toughness
Titanium and titanium alloy Non-resorbable
Cobalt-chromium alloy • and plasticity

Inorganic compounds
Calcium sulfate • Bioresorbability Low toughness
Calcium phosphate • Osteoconductivity and plasticity
(e.g. hydroxyapatite)

Elgali I, Omar O, Dahlin C, Thomsen P. Guided bone regeneration: materials and biological mechanisms revisited. Eur J Oral Sci. 2017 Oct;125(5):315-337. doi: 10.1111/eos.12364. Epub 2017 Aug 19. PMID: 28833567; PMCID: PMC5601292.
Non-resorbable membranes Resorbable membranes

1. PTFE (polytetrafluorethylene) A. Synthetic polymers- Biodegradation by Kreb’s cycle into

2. ePTFE (Expanded CO2 and H2O.

polytetrafluorethylene) • Polyglycolides (PGAs),

3. dPTFE (High-density PTFE) • polylactides (PLAs), or copolymers thereof
4. Titanium-reinforced PTFE • polydioxanones
5. Titanium mesh • trimethylene carbonates
B. Polymers derived from animal resources(Collagen)
• bovine tendon, bovine dermis, calf skin, porcine dermis,
and human skin from cadavers.
• Cross-linked collagens exhibit membrane ossification
Collagen cross-linking agents- ultraviolet light, formaldehyde, glutaraldehyde, diphenyl phosphoryl
azide, and hexamethylene diisocyanate.
Glutaraldehyde technique left cytotoxic residues.
Membrane modifications may trigger membrane ossification.
The membrane of choice for most GBR cases
- Non-cross-linked collagen membranes
The membrane of choice for vertical augmentation procedure
- dPTFE

30 years of guided bone regeneration / edited by Daniel Buser, ISBN: 9780867158038

 Bone promotive effects of GBR membrane

upregulation of bone formation genes(e.g, OP, BSP,

ALP) after 3 weeks of healing.
enhanced expression of GFs, inflammatory cytokines
and bone remodelling proteins.
Fine-tuning of expression of TNF-α under collagen
barrier.
host cells that express and secrete pro-osteogenic and
bone-promoting factors,

Elgali I, Omar O, Dahlin C, Thomsen P. Guided bone regeneration: materials and biological mechanisms revisited. Eur J Oral Sci. 2017 Oct;125(5):315-337. doi: 10.1111/eos.12364. Epub 2017 Aug 19. PMID: 28833567; PMCID: PMC5601292.
 Potential strategies to enhance the
clinical results of the GBR technique

• Optimization of the membrane porosities.

• Incorporation of biological factors, natural
elements and synthetic bioactive materials
• Incorporation of antibiotics and antibacterial
agents.
• Administration of osteoconductive and
osteoinductive bone grafts.
• Administration of biological cues into the bone
defect.
 References

• 30 years of guided bone regeneration / edited by Daniel Buser, ISBN: 9780867158038

• Rusin Zhao;Ruijia Yang;Paul R. Cooper;Zohaib Khurshid;Amin Shavandi;Jithendra Ratnayake; (2021). Bone
Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments . Molecules, (), –.
doi:10.3390/molecules26103007
• Hallman M, Thor A. Bone substitutes and growth factors as an alternative/complement to autogenous bone for
grafting in implant dentistry. Periodontol 2000. 2008;47:172-92. doi: 10.1111/j.1600-0757.2008.00251.x.
PMID: 18412581.
• Omar O, Elgali I, Dahlin C, Thomsen P. Barrier membranes: More than the barrier effect?. J Clin Periodontol.
2019;46(Suppl. 21):103–123. https://doi. org/10.1111/jcpe.13068
• Dahlin, C. (2010). Optimal implant placement in the esthetic zone by the use of Guided Bone Regeneration. In L.
Andersson, K.-E. Kahnberg, & M. A. Pogrel (Eds.), Oral and maxillofacial surgery (pp. 357–366). Chicago, IL:
John Wiley & Sons Ltd..
• Elgali I, Omar O, Dahlin C, Thomsen P. Guided bone regeneration: materials and biological mechanisms revisited.
Eur J Oral Sci. 2017 Oct;125(5):315-337. doi: 10.1111/eos.12364. Epub 2017 Aug 19. PMID: 28833567; PMCID:
PMC5601292.
• Buser D, Hoffmann B, Bernard JP, Lussi A, Mettler D, Schenk RK. Evaluation of filling materials in membrane-
protected bone defects. A comparative histomorphometric study in the mandible of miniature pigs. Clin Oral
Implants Res 1998;9:137–150.
• Jensen SS, Bornstein MM, Dard M, Bosshardt DD, Buser D. Comparative study of biphasic calcium phosphates
with different HA/TCP ratios in mandibular bone defects. A long- term histomorphometric study in minipigs. J
Biomed Mater Res B Appl Biomater 2009;90:171–181.
Thank You