Bone Grafts and Substitutes in

Dentistry: A Review of Current Trends

and Developments
Rusin Zhao 1 , Ruijia Yang 1, Paul R. Cooper 1, Zohaib Khurshid 2 , Amin Shavandi 3
and Jithendra Ratnayake 1,*

Presented by Dr Monika
MDS First year
Department of Prosthodontics
BONE
 INTRODUCTION
• A bone graft is defined as a living tissue capable of promoting bone healing,

transplanted into a bony defect, either alone or in combination with other

materials.

• A bone substitute is a natural or synthetic material, often containing only a

mineralized bone matrix with no viable cells, that is able to achieve the same

purpose.
• According to the US Food and Drug Administration (USFDA), bone grafts

are classified as Class II devices (bone grafts filling the bony voids and

defects) and Class III devices (bone graft containing drugs).

• The use of bone grafts and substitutes in dentistry have markedly

increased in recent years due to advancements in dental implantology

and the growing need for repair of craniofacial bony defects.

• These bony or skeletal defects may arise from trauma, periodontal

disease, surgical excision, cranioplasty, infection or congenital

malformations, and oral cancer.

• The most common observation of insufficient quantity of bone in

dentistry is following tooth loss, where rapid resorption of alveolar bone

occurs due to an absence of intraosseous stimulation that would

typically occur via the periodontal ligament fibers.

• Successful placement of dental implants requires sufficient alveolar

bone dimensions, that is, at least 10 in height and 3 mm to 4 mm in

diameter.

• It has been estimated that up to 50% of all dental implant procedures

• These primarily involve the use of allografts and autografts.

• None of the products in the market currently possesses all the ideal

properties for a bone substitute material including

 low patient morbidity,

 ease of handling,

 low immunogenicity,

 low cost

 angiogenic potential.
• The disadvantages of autografts include the

 lack of availability of graft tissue,

associated pain,

 morbidity at the donor site

the need for two operative procedures

• The disadvantages of allografts include

rejection of the donor tissue by the recipient’s immune system

concerns with transmission of diseases, such as HIV and hepatitis

• This literature review reports on the dental bone graft and substitute

materials that are currently available commercially, their limitations, and

the potential development of promising alternatives brought about by the

emergence of synthetic bone substitutes in recent decades.

 Characteristics of ideal bone grafting
materials
• The main function of bone grafts is to provide mechanical support and

stimulate osteo-regeneration, with the ultimate goal of bone replacement.

• The four fundamental biological properties of

 osseointegration

 osteogenesis

 osteoconduction,

 osteoinduction, are paramount in performing this role effectively.

Osseointegration
• The ability of a grafting material to chemically bond to the surface of the
bone in the absence of an intervening fibrous tissue layer is referred to
as osseointegration.
Osteogenesis
• Osteogenesis refers to the formation of new bone via osteoblasts or
progenitor cells present within the grafting material.

Osteoconduction
• Osteoconduction refers to the ability of a bone grafting material to
generate a bioactive scaffold on which host cells can grow.

• This structure enables vessels, osteoblasts and host progenitor cells to

migrate into the interconnected osteomatrix .
Osteoinduction
• Osteoinduction is the recruitment of host stem cells into the grafting
site, where local proteins and other factors induce the differentiation of
stem cells into osteoblasts.

• Multiple growth factors influence this process, including

• platelet-derived growth factors (PDGFs),

• fibroblast growth factors (FGFs)

• transforming growth factors- (TGFs-).

• These four fundamental properties enable new bone formation which

occurs in parallel to direct osseous interconnection .
• Additionally, various other properties will influence the success rate of a bone

graft.

• These include, but are not limited to,

 biocompatibility,

 bioresorbability,

 sterility,

 structural integrity,

 adequate porosity for vascular ingrowth,

 plasticity,

 ease of handling,

 cost,

 compressive strength .
Classification of dental bone graft and
substitute materials
 1. Natural Bone Graft and Substitute
Materials
• Materials of natural origin are defined as those that have been derived

from a living source without modification.

• These materials can be further subdivided into four subcategories:

• autografts,

• allografts (such as demineralized bone matrix (DBM)),

• xenografts,

• phytogenic materials.

• It has been estimated that up to 90% of all bone grafting procedures

 Autografts
• Autografts are commonly obtained from intraoral and extraoral sites from the same

individual, such as the mandibular symphysis, mandibular ramus, external oblique ridge,

iliac crest, proximal ulna, or distal radius, due to being good sources of cortical and

cancellous bone.

• Mandibular ramus grafts are appropriate for use when the sites requiring augmentation

are less than 4 mm in thickness and span a maximum of four teeth.

• No histocompatibility and immunogenicity issues associated with autografts, therefore they

represent the highest degree of biological safety.

• However, there are several downsides associated with autografts, such as the

• requirement for a secondary surgical visit,

• donor site injury

• the potential for scarring.

• Autografts have been associated with

• higher surgical costs

• more significant surgical risks, e.g.,

• excessive bleeding,

• infection,

• inflammation and pain, limiting their application to relatively smaller bone defects
• Cancellous bone is most commonly used for autografts and contains

osteoblasts and progenitor cells with considerable osteogenic potential.

• In contrast, cortical bone lacks osteoblasts and osteogenic cells; instead,

it provides structural-mechanical integrity and promotes bone healing

through osteoconduction.

• Cortical grafts are slower to integrate relative to cancellous grafts due to

their limited revascularization potential.

• Therefore, to maximize bone remodeling performance and healing

potential, a combination of cancellous and cortical bone is used.

• In dental applications, even though other bone substitutes are routinely

used for management of localized alveolar bony defects and maxillary

sinus bone grafting, autografts in block forms are still routinely used in

alveolar ridge augmentation procedures.

 Allograft
• The primary alternative to an autograft is the use of allograft materials, which can be

obtained from either a compatible living donor or from cadaveric bone sources.

• Allograft materials can be prepared in three primary forms—

• fresh,

• frozen, or

• freeze-dried.

• Fresh and frozen allograft materials possess superior osteoinductive properties but

are rarely used nowadays due to the higher risk of a host immunogenic response,

limited shelf life, and increased risk of disease transmission.

• In recent decades, the use of allograft materials has often been preferred.

• Allografts have been successfully used in combination with xenografts for guided
bone regeneration (GBR) in bone augmentation procedures.

FIGURE ; Clinical images illustrating the pre- and post-operative (post-op) procedures of an edentulous patient treated with
an implant with guided bone tissue regeneration. Images from left to right show: (a) the edentulous site after the tooth was
extracted; bone defect in the form of buccal concavity is visible in the apical aspect of 24 (yellow arrow). (b) Occlusal shot of
the edentulous site showing the buccal concavity. (c) The correct positioning of the implant (Straumann Bone Level Tapered
3.3 × 10 mm implant). (d) Proper bucco-palatal positioning of the implant
(e) Decorticated area to prior to placement of the bone and complete absence of the buccal bone at the apical part of the
implant. (f) The placement of Straumann Flex Membrane fixed and stabilized by tacks (AutoTac by BioHorizons Canada).
(g) Applying bone graft particles comprising of a mixture of Allograft and Xenograft (both from Straumann®) packed at the
buccal bone defect. (h) Periosteal sutures used to stabilize and fix the bone graft inside the membrane, which ensures
immobilization of graft resulting in optimal bone regeneration vs. fibrous tissue formation. (i) Primary closure of the site. (j)
Showing post-op. Primary closure is intact. (k) The implant after second stage and osseointegration check. (l) Five months later,
post-op cone beam computed tomography (CBCT) illustrating the final bone healing prior to second stage and osseointegration
check of the implant.
The post-op CBCT revealing a gain of over 5 mm of bone
• . In dental applications, allografts have been used to fill periodontal, maxillary, and

mandibular defects .

• Block allografts have routinely been used to restore deficiencies in alveolar ridge height

or severe ridge atrophy to allow for sufficient bone height for implant placement.

• In recent years, concerns relating to the shortage of tissue supply, as well as findings of

high failure rates following long-term use have led to a decline in the application of

allograft materials.
• DBM provides a lack of structural support and thus possesses poor mechanical

properties.

• Therefore, the use of DBM is only limited to filling bone defects and is generally used in

combination with other allografts, BMPs or composite bone substitute materials.

• Human DBM in putty form has been successfully used to preserve and restore alveolar

bone height and thickness following tooth extraction, resulting in the formation of

mineralized and mature bone six months after grafting.

• Collagen-based materials, such as extracellular bone matrix are another allograft derived

material available in the market.

• These materials can provide a favorable environment for new bone formation through

mineral deposition, vascularization, and growth factor adhesion.

• However, collagen-based materials present a high potential for adverse immune

reactions and possess poor structural integrity.

• Therefore, it is generally considered a poor graft substitute alone, although it can

improve osseointegration when incorporated with BMPs or a hydroxyapatite carrier.

 XENOGRAFT
• Xenografts are grafting materials that are derived from a genetically unrelated species from the host .

• The most common source of xenograft materials in the dental field is deproteinized bovine bone which

is commercially available as BioOssTM.

• Bovine bone is treated with a stepwise annealing process followed by chemical treatment with NaOH

to produce a porous hydroxyapatite (HA) material containing only the inorganic components of bovine

bone.

• The resulting porous structure highly resembles that of human bone and can provide good mechanical

support and stimulate bone healing through osteoconduction.

• The porous structure exhibits a vast surface area, and promotes the growth of new blood

vessels via angiogenesis which enhances bone growth.

• Bovine bone substitutes have been used extensively in maxillary sinus lifting and implant

procedures due to their superior stability and low immunogenicity.

• Studies have found that maxillary sinus defect sites grafted with BioOssTM resulted in

39% new bone formation after 6 months, which was comparable to 40% new bone

formation following grafting with autograft bone after the same time period.
• Furthermore, they found that 31% of grafted BioOssTM remained at the graft site,
compared with just 18% of the autograft bone.

• These statistics suggest that the efficacy of BioOssTM in stimulating new bone formation
closely matches, if not exceeds, that of autograft bone.

• A 5-year prospective follow-up study conducted by Ozkan et al. (2011) also found that
sufficient quality and volume of bone, allowing for predictable simultaneous placement of
implants, resulted from bovine bone grafts following one-stage maxillary sinus
augmentation procedures.

• Clinically, BioOss has proven to be a valuable bone substitute material providing good
quality of new bone and promising long-term survival rates following dental surgery.
• Other commercially available products based on bovine bone are also available, such as

OsteoGrafTM and CeraboneTM .

• Both of these products are high temperature treated, thus eliminating all organic

components, which result in a product that possesses low immunogenicity.

• Like BioOssTM, these products exhibit very similar structural and biochemical properties

to human bone and can act as effective osteoconductive grafting materials

• A promising xenograft material currently being researched is chitosan, a naturally occurring

polymer derived from the exoskeletons of crustaceans composed of glucosamine and N-

acetylglucosamine.

• Chitosan is available in a variety of forms, including beads, films, hydrogels, and more complex

structures, such as porous scaffolds.

• Wattanutchariya and Changkowkai found that mixing chitosan with gelatin and hydroxyapatite

(HA) produces a porous scaffold with more desirable properties, including decreased

degradability and an open pore structure conducive to cell attachment and vascularization.
• Recent studies in the dental field have reported the successful use of chitosan-based
materials as a membrane for GBR, guided tissue regeneration, coating implant surfaces,
periodontal regeneration and restoring alveolar bone height.

• Silk is a natural biopolymer obtained from the silkworm Bombyx mori.

• It is predominantly composed of the proteins, fibroin and sericin.

• After removal of sericin through degumming, silk fibroin (SF) is commonly used as a bone
scaffold in sponge, fibers, film and hydrogel forms.

• SF demonstrates excellent biocompatibility, degradability, tissue integration, oxygen and

water permeability.

• Recent research has shown that silk’s favorable biological properties enable its use as a
membrane for GBR despite its poor mechanical properties.
 Phytogenic material
• Phytogenic materials are bone substitute materials obtained from a plant-based origin, such as

Gusuibu, coral-based bone substitutes, and marine algae.

• This material has been shown to possess osteoinductive properties, increased alkaline

phosphatase activity, and thus promotes bone calcification and remodeling processes.

• In dental applications, Gusuibu has been shown to accelerate bone remodeling following

orthodontic tooth movement through promotion of osteoblastic activity, and cell culture studies

have revealed that Gusuibu is able to mediate bone remodeling through regulation of osteoclast

and osteoblast activity.

• Coral-based bone substitutes are predominantly composed of calcium carbonate used either in

its naturally occurring form or processed by heat treatment with ammonium phosphate and

converted into crystalline HA which subsequently has minimal residual carbonate.

• Coralline HA-based materials used in dentistry have varying pore sizes and exhibit good

compressive strengths, low immunogenicity, good bone bonding capacity, however they have

relatively low tensile strengths, brittleness and poor resorption.

• These materials have been used for procedures such as maxillary sinus lifting, periodontal

osseous defects and alveolar reconstruction for placement of dental implants.

• AlgiPoreTM is a naturally occurring HA derived from marine algae that has been clinically

used as a bone substitute material since 1988.

• This material possesses desirable properties such as good resorbability over time, a large

surface area for protein adhesion, and low immunogenicity.

• Clinically, AlgiporeTM has mostly been used as a space filler, in combination with other

materials following tooth extraction to prevent ridge deformities.

 2. Synthetic Bone Substitute
Materials
• To overcome potential immunogenicity and morbidity at donor sites, artificial synthetic

bone substitute materials are generated to closely mimic the biological properties of

natural bone.

• Despite this, currently available synthetic materials display only osteointegrative and

osteoconductive properties.
• Materials that fall into this category include calcium phosphate ceramics, such as

• hydroxyapatite (HA),

• tricalcium phosphate (TCP) and

• bioglass;

• metals, such as nickel-titanium;

• polymers, such as polymethylmethacrylate (PMMA), and polyglycolides and calcium

phosphate cements.
 3.Growth Factor-Based Bone
Substitutes (GFBSs)
• Growth factors (GFs) such as BMPs, platelet-derived growth factors (PDGFs) and insulin-like

growth factors (IGFs) have been found to possess osteoinductive properties, allowing for

accelerated bone regeneration in bony defects.

• In the dental field, the first use of bioactivated materials with growth factors is in the use of

plasma rich in growth factors (PRGF), platelet rich plasma (PRP) and plasma rich in fibrin

(PRF) to accelerate bone healing in patients with bisphosphonate related osteonecrosis of

the jaw (BRONJ).

• Recent studies have revealed varying results which cast doubt on whether the additional use

of PRP with other grafting materials in the treatment of infrabony defects and sinus

augmentation provides any added benefits.

• Since the early 2000s, BMP-2 and BMP-7 have been the most commonly used USFDA

approved growth factors for bone grafting procedures in dentistry and function as the active

components of two major commercial products—InfuseTM and OsigraftTM, respectively.

• However, the production of OsigraftTM has since been halted and the use of InfuseTM has

been associated with a large number of life-threatening complications

• Sticky bone is another recently developed concept which utilizes a bone graft matrix enriched with growth

factors using autologous fibrin glue.

• The use of sticky bone is able to stabilize bone graft material in bony defects allowing for accelerated bone

regeneration and minimizing bone loss.

• The advantages of this material include good moldability, good structural stability, selectivity for osteogenic

progenitor through prevention of soft tissue cell migration via fibrin interconnections; and fibrin network

allowing for rapid cell adhesion and accelerated healing.

• When used in combination with a concentrated growth factor (CGF) membrane, or titanium mesh, grafting

with sticky bone in an atrophic alveolar ridge resulted in favorable three-dimensional ridge augmentation

over a 4-month period.

4. Bone Substitutes with Infused Living
Osteogenic Cells

• Viable osteogenic progenitor cells, such as MSCs, can be used alone or in combination

with other materials such as cytokines, GFs and scaffolding carriers and carriers including

DBM to stimulate new bone formation and enhance bone healing through

osteoconduction and osteogenesis.

• MSCs are non-hematopoietic multipotent cells routinely derived from bone marrow .
• They are able to differentiate into osteogenic cells and can regenerate large bone defects

when used with a scaffolding carrier.

• Studies have shown that bone substitute materials that are bioengineered with MSCs can

markedly improve bone healing and reconstruction when compared with the use of MSCs

alone or a bone substitute material in the absence of MSCs.

• The resulting new bone formed displays significantly improved biomechanical performance

and thus improves the rates of successful placement of dental implants.

• Direct infusion with MSCs can promote more rapid and consistent bone healing.
• Clinically approved products available commercially for dental use include Bioseed-Oral

BoneTM and Osteotransplant DENTTM, which utilize an autologous source of MSCs with

an appropriate scaffold.

• These products are indicated for use in sinus augmentation of severely atrophic maxilla

to achieve predictable implant placement.

 Future of Bone Substitute Materials in
Dentistry
• Despite the establishment of criteria defining the ideal bone grafting material several decades ago, to

this day, autografts remain the gold standard and only material that possesses all four fundamental

biological properties.

• However, their limited availability and other associated limitations discussed previously have driven a

shift towards using alternative grafting materials and the development of novel synthetic bone

substitutes.

• Producing a mechanically strong, interconnected porous structure allowing for ideal osseointegration

and vascularization has been identified as the major difficulty faced in material development.
• Regrettably, synthetic bone substitutes only possess osteoconductive properties where

bone regeneration is restricted to the outer surface layer.

• This supports the need for the careful structural design of new materials including

considering vital biological parameters such as pore size, density, morphology and

interconnectivity and resorbability.

• There has been a recent trend for the incorporation of osteoinductive growth factors

and/or MSCs with a structural scaffold to increase the material’s bone regenerative

potential and inhibit undesirable inflammatory recipient responses.

• Additionally, there has also been increasing interest in the controlled time-release delivery of
growth factors as a means of maintaining their bioactivity over the therapeutic window.

• Thus, the development of novel grafting materials should focus on incorporating as many
ideal biological parameters as possible, whilst ensuring that such materials would be readily
available, cost-effective and clinically evidence based.

• Another major challenge we face is the lack of research investigating the safety and efficacy
of newer bone grafting materials.

• Most of the information available regarding these newer materials are derived from case
reports or experimental animal models, and thus the reliability of this information may be
questionable.
 Conclusion
• Bone graft and substitute materials which are either in the form of particulate or blocks are

mostly used in dentistry to regenerate the missing hard tissue structures.

• There is a high and growing demand for new and more efficient dental grafting materials.

• Current bone graft and substitute materials primarily serve as a structural framework for

osteo-regenerative processes that only satisfy the osteoconductivity criteria.

• Development of hybrid grafts which utilize growth factors and living osteogenic cells capable

of inducing bone regeneration presents the future of dental bone grafting and dental implants.
• Good examples include bone substitutes that can release bone morphogenic proteins or

platelet-derived growth factors in a controlled manner.

• Despite the progress highlighted in this review article more work is needed to develop

dental biomaterials that have a porous structure, mechanically stability, controlled

degradation, and remodeling ability which is comparable with the rate of new bone

formation.