Engineering of Bone Tissue for augmentation procedures

By Dr. Amir Kraitzer

RequirementsCurrent solutionsBi-Phasic Calcium Sulfate

Outline

1. Overview2. Bone and Bone Augmentation3. Bone graft materials4. Bi-Phasic calcium sulfate Bone Graft – Bond

Bone

Bone Augmentation• The past decade brought a new era in

bone repair fueled by the latest technological advances

• Part of the routine surgical spine, orthopedics and dental care

• New methods and new bone grafts facilitated grafting procedures

• Bone graft sources: – The patient itself– Cadavers– Animals– Synthetic

• ~500,000 bone graft procedures performed in US yearly ~ 2.2 million worldwide• Estimated cost of $2.5 billion per year• Dental bone graft estimated cost 8% of total bone graft

Periodontal disease • Account for ~60% of tooth loss• Affect one or more of the

following tissues:– alveolar bone – periodontal ligament – cementum – gingiva

• Bacteria and plaque cause toxins eventually lead to inflammation

Outline

1. Overview2. Bone and Bone Augmentation3. Bone graft materials4. Bi-Phasic calcium sulfate Bone Graft – Bond

Bone

Bone augmentation• Following tooth extraction the alveolar ridge resorbes• Early bone loss can be reduced by socket grafting• Augmentation replaces missing bone• Grafting materials are implanted and fused with natural bone over time• Granular or block type grafts require membrane due to particle

migration• Grafting procedures repair jaw bone defects:

– periodontal defects– post extraction defects– bone reconstruction– implant placement– Infections– cyst or tumor surgery defects

Bone Augmentation:http://www.toothiq.com/dental-videos/dental-video-bone-resorption.html

Augmentation Procedures• Grafting procedures performed primarily by

periodontists or experienced dentists• Require wound healing understanding • Require knowledge of the mechanical, material

and biological properties of the graft

Sinus lift procedure

Bone Structure

• Mineralized component: 60% of the bone is hydroxylapatite crystals: Ca10(PO4)6(OH)2

• Organic matrix: 40% of the bone mostly collagen

• Cellular components:– Osteoprogenitor cells– Osteoblast– Osteocyte– Osteoclast

• Blood supply:– Receives 5 - 10% of cardiac output– Arterial supply– Microcirculation– Venous return

Bone is a highly ordered structure on the macroscopic, cellular and molecular levels.

Bone BiologyOsteoblast • Bone forming cell• Responsible for deposition and calcification of bone matrix• Osteoblasts synthesize collagen and other proteinsOsteocyte• Mature, fully differentiated osteoblast • Surrounded by mineralized bone matrix Osteoclast• Responsible for the resorptive aspect of bone remodeling• Elaborates enzymes, acids for resorption of bone matrix Osteoprogenitor Cells • Pluripotential cells• Stem cells• Bone marrow stromal cells

Bone StructureBone may be classified on the basis of its clinical structure• Compact Bone (cortical) - Dense,

solid bone such as the outer cortical layer

• Trabecular bone (spongy or cancellous bone) - non dense bone located between compact bone.

Bone anatomy and microstructure http://www.youtube.com/watch?v=c5zcGv8MvMc&feature=relatedhttp://www.youtube.com/watch?v=ylmanEGjRuY&NR=1&feature=fvwp

Bone Structure development

Cortical or cancellous bone is of two main types • Woven (embryonic) Bone

– Immature– rapidly forming bone– Randomly distributed oseocytes– poorly mineralized – structurally weak– replaced with lamellar bone

• Lamellar Bone– Mature bone– Arranged parallel collagen fibers , HA and bone cells– Main load bearing component of the bone– Slowly formed (approximately 0.6 to 1 mm/ day)

Bone Modeling and Remodeling

• Bone is capable of self-repair and adapts new loads (Wolff’s Law)

• When stimulated under load the cortical portion of bone becomes thicker

• Bone becomes weaker without stimulus • Two fundamental concepts, modeling and remodeling,

describe the dynamic nature of bone– Remodeling - Osteoclastic resorption and osteoblastic

formation is balanced– Modeling – Bone changes its 3D size and shape in response

to stimulus or physical forceBone formation: http://www.youtube.com/watch?v=X6E5Rz9tOKE&feature=related

Tensile Strength (MPa) and % elongation at break of cortical bone from the human femur as a function of age

BONE TISSUE MECHANICAL PROPERTIES

OstseoporosisA disease of bones that leads to an increased risk of fracture. Remodeling imbalance between bone resorption and bone formation

Healthy bone Osteoporosis

Outline

1. Overview2. Bone and Bone Augmentation3. Bone graft materials4. Bi-Phasic calcium sulfate Bone Graft – Bond

Bone

Mechanisms of Graft HealingAn ideal bone graft should possess the properties involved in bone healing

(1) Osteoconductive – Matrix providing 3D lattice with interconnected pores– Allowing cells to migrate for ingrowth of new blood vessels and

osteoprogenitor cells

(2) Osteoinductive – Recruit and encourage migration of osteoprogenitor cells– Stimulating factors towards osteoblastic differentiation

(3) Osteogenic – Formation of new bone from living cells transplanted within the graft

Bone Grafting MaterialsClassification of Grafting Materials Based on Source• Autograft (Autogenous) - Refers to a transplant of viable

cortical or cancellous bone from one location to another within the same patient

• Allograft- Refers to a transplant within the same species, such as the human bone sourced from cadavers.

• Xenograft- Refers to a cross-species transplantation such as the use of anorganic bovine bone or bovine collagen in human subjects

• Alloplast- Refers to implantation of a synthetic material. As a group, the alloplasts are synthetic osteoconductive materials.

Bone Grafting Materials

Autograft • Considered the gold standard• Osteoinductive, osteoconductive, and osteogenic properties • The risk of infection is minimal• Bone is harvested from mouth, hip, iliac crest or chinDisadvantages• Low availability of bone volume• Require a second operative site• Significant patient morbidity

Bone Grafting MaterialsAllografts• Human cadavers source• Mineralized freeze dried allograft

– Osteoconductive and Osteoinductive – Low bioavailabilty and activity of bone morphogenetic proteins (BMP)

• Demineralized freeze dried bone– Osteoinductive – The process exposes BMP

• BMP cause differentiation of mesenchymal cells into osteoblasts Disadvantages• Lack of uniformity in the products of individual banks• Risk of disease transmission and unpredictability• Possible infections, and antigenicity risks

Grafton® DBM Gel

Bone Grafting MaterialsXenograft• Naturally derived hydroxylapatite from bovine, coral• Osteoconductive • Similar structure, chemistry, and porosity of human boneDisadvantages• Risk of disease transmission• Remains in the defect for years • Continuous macrophage activity

Histology review: http://www.youtube.com/watch?v=bTP2hAG0wcM&feature=channel

Alloplast synthetic graftsDense Hydroxylapatite • High density, high crystallinity and no resorption over time• Particles placed adjacent to bone become surrounded by bone• Particles placed more than a few millimeters are surrounded by fibrous connective

tissueLow-Density Hydroxylapatite • Plasma-sprayed HA applied to implant surfaces• Amorphous • ResorbableBeta-Tricalcium Phosphate• Granular Matrix type:

– Porous particles (100-300 μm) pore size– Resorbed and replaced by bone in 9 to 12 months

• Cement Type: – Injected and hardens in 12 hours

Alloplast synthetic grafts/more

Bioglass • Amorphous • Composed of calcium phosphate, sodium, and silicon • Bioactive layer for bone cell attraction to form a HA layer Bioplant HTR®• Polymethyl methacrylate (PMMA) beads with a calcium

hydroxide (CH) coating• Porous (350 μm) to facilitate bone ingrowth• Partially resorbable (CH)

Ideal Synthetic bone graft• Materials – HA or HA forming materials

• Pore size, distribution, and porosity (matrix graft)– Pores of 100 mm form bone (Pores of 15-40 mm produce fibrous tissue)– Pore of 300-500 mm permit vascular in-growth– Interconnected pores

• Granule size (granular graft)– Grains larger than 10 mm prevent stimulation of macrophage phgocytosis

• Crystalline structure – Affect the surface adsorption of osteogenic cells– Affects mechanical and resorption profile

• Mechanical properties– Should be in close proximity to the mechanical properties of bone

Stress Shielding

• Reduced bone density due to removal of stress by an implant

• Stimulus for remodeling is required to maintain bone mass (Wolff's law)

• We must select materials which are in close proximity to bone’s mechanical properties

Density(g/cm3)

Elastic modulus (GPa)*

Yield strength(MPa)

Tensile Strength (MPa)

% Elongation at break

SS 316L30% cold worked

7.9 190 690 860 12%

Ti-6Al-4V or ASTM F136

annealed

4.5 114 830 900 14 %

PLLA 1.3 2.7 -- 50 5 -10%

Density(g/cm3)

Elastic modulus (GPa)*

Compressive Strength(MPa)

Tensile Strength (MPa)

% Elongation at break

Cortical Bone ~2 17 - 24 100-230 90-130 1-3%

CancellousBone

~1 0.1 - 4.5 2-12 10-20 5-7%

*In tension

Resorption rate• In the early phase of healing material should remain stable• Resorbtion rate should correlate the rate of bone formation

– Fast resorption compromise the osteocoductivity – Slow resorption may block bone in-growth

• Homogenous solubility– Prevent premature microparticles separation– Reduce macrophage phagocytosis– Assist bone-forming metabolism

• constant physiological concentration of calcium and phosphate ions

Actifuse compared to β-TCP (VitossTM) and calcium sulfate (Osteoset TM) in the distal femoral condyle of the New Zealand white rabbit

Actifuse (Ca-Po with silicate ions replaced phosphate groups in the calcium phosphate ionic lattice)

Novel Bi-Phasic Calcium sulfate bone graft

Alderman, 1969;

Bahn, 1966 ;

Bell, 1964 ;

Coetzee, 1980 ;

Edberg, 1930 ;

Gitelis et al., 2001 ;

Kelly et al., 2001 ;

Peltier and co-worker, 1957;

Peltier and Lillo, 1957 ;

Peltier and Orn, 1958 ;

Peltier and Speer, 1981 ;

Peltier et al., 1957 ;

Peltier, 1959 ;

Peltier, 1961 ;

Robinson et al., 1999 ;

Silveira et al., 2008 ;

Tay et al., 1999 ;

Calcium Sulfate (CS)

• Long history of use as a void filler• First used in 1892 by Dreesmann in

orthopedics • Highly biocompatible• Osteoconductive • Fully resorbed over a period of 5–7 weeks• New bone formed in a normal morphology

The Bi Phasic Calcium Sulfate Concept

Advantages• High strength• Resorption rate

equivalent to bone growth

• Is not affected by blood and saliva

Advantages• Moldable• Cementable

HemihydrateCaSO4 · 0.5H2O

Dihydrate CaSO4 · 2H2O

Disadvantages• Does not set in presence of

blood/saliva• Low strength• Fast resorption

Disadvantages• Non-moldable• Non- cementable

CS HemihydrateCS Dihydrate+

Bi–Phasic Calcium Sulfate

Fast and efficient setting under blood and saliva (2-5 min) High crystalline percentageResorbtion rate equivalent to bone growth (4-10 weeks) Moldable Average reaction temperature - 30°C Neutral pH Preserves the 3D spaceMechanical properties equivalent to bone

Bi – Phasic CS Advantages

Thank you

• Facilitate treatment• Enhanced resorption rate

– Composite bone graft with various rates of resorption– Osteoconductive only when required

• Effective and safe biological activity– Promotion of osteoblastic proliferation, differentiation and function

Future of Bone Grafts