Biomimetic (Latest)

BIOMIMETIC
DENTISTRY
• "Bio" meaning life
"mimetic" related to imitate biochemical process from
nature
Biomimetic Aspects • Biomimetics refers to the repair of affected dentition
of Restorative mimicking the characteristics of a natural tooth in terms of
Dentistry appearance, biomechanical, and functional competences
Biomaterials
Sohail Zafar m. 2020

BIOMIMETIC PERSPECTIVE
 Mechanical
 Aesthetic
 Biocompatibility
 Tissue-Engineering Aspects
 Remineralization
DENTAL
HARD
TISSUES
Enamel
• Highly mineralized crystalline lattice structure of HA
• brittle and higher elastic modulus and compressive strength compared to resilient and flexible
dentin
• Enamel has a hard, dense crystalline structure, still permeable pass through rod sheaths due to
crack formation and hypomineralization

Dentin-Pulp Complex (DPC)
• Dentin is composed of inorganic and organic material
• Dentin and pulp are considered to a single tissue unit, that the integrated dynamics of DPC
impact not only the quality and quantity of dentin but also the pulpal component

Cementum
• Cementum is composed of inorganic, organic matrix (collagen and proteins) and water
• Acellular cementum (without cementoblasts) is present in the coronal portion
• Cellular cementum is associated with the apical half of root structure

 Mechanical
 Aesthetic
Biomimetic Mechanical Perspective of
Restorative Materials
• Elasticmodulus
• Surface hardness
Elastic modulus
• Elastic modulus of dental restorative materials should be harminized with tooth
→ to facilitate uniform sharing of stresses in the tooth-restoration interface

• The discrepancy of elastic modulus across tooth-restoration interface enhance the probability of
fracture of remaining tooth structure and bonding may fail to microleakage and secondary caries

Surface hardness
• Surface hardness of restorative materials should closely match to hardness of tooth structure

• Lower SH are more susceptible to abrasion in surface wear and porosity

• The restoration of severely damaged teeth, an alternative to cuspal coverage is direct restorations
utilizing short fiber-reinforced composite (FRC) materials
• The direct restorations with FRC material comprise 2 layers

• FRC base covered with resin composite
Bijelic D,2019
• FRC base > > Multidirectional irregular
• Main advantage is the fracture pattern deviation from
non-reparable to restorable
• Properties of short FRC
• High aspect ratio (Lc/d) → everX Posterior
• Lc : critical fiber length
• d : diameter
• Fiber loading
• Fiber orientation
Bijelic D,2019
Adhesion between everX Posterior and conventional composite is a key factor
The fibers in everX Posterior increase the adhesion to overlying

composite by providing mechanical retention
• The anatomical placement of short FRC with cusp-supporting design will enhance chewing
fracture resistance of damaged teeth
Limiting the thickness of

The cusp-supporting
overlaying material to
design is to substitute all
equal the enamel
lost dentin tissue
thickness
Bijelic D,2019
Most of the direct composite restorations without a short-FRC base fractured unfavorably with or
without endodontically for 75%
The anatomical cusp-supporting short-FRC base design provided enhanced resistance to fracture and
preserved tooth integrity by stopping the fracture propagation towards the CEJ and the root
Bijelic D,2019
• Short FRC is dentin-like in two aspects,
• structurally (short fibers resembling the collagen network in dentin)

• mechanically (having flexural modulus, tensile strength and fracture toughness close to
dentin)
Absorb and distribute the occlusal stress
Bijelic D,2019
Catastrophic non-restorable
Restorable fracture of biomimetic
fracture of direct composite resin
bilayered restoration in ETT
restoration in non-ETT
Non-restorable fracture of
Possibly restorable fracture of direct composite resin restoration
biomimetic bilayered restoration in in ETT
non-ETT
Bijelic D,2019
 Mechanical
 Aesthetic
Aesthetic Perspective of Restorative
Materials
• Resin composite are presently the direct restorative materials that has conservative, aesthetics and
durability
• In recent years, porcelain veneers have become the treatment of choice for restoration of anterior
teeth in terms of morphology and optical properties and mimicking natural enamel.
Bijelic D,2019
 Mechanical
 Aesthetic
Biocompatibility of
Dental Restorative Materials
Ideally, a restorative dental material or

its breakdown products
should not incite any allergic or toxic reaction
Biocompatibility of
Chemical/light-cured RDCs and GIC:

cytotoxic reactions following initial setting
and further decreased soon
Goldberg M. 2008
Gao W. 2001
Biocompatibility of
Dental porcelains :
- highly stable and insoluble → bioinert, highly biocompatible
Matinlinna J. 2007
Ho G. 2011
BIOMIMETIC
MINERALIZATION
OF ENAMEL AND
DENTIN
Biomimetic mineralization
Enamel
• synthesis of enamel-like apatite structures
• enamel biomimetic mineralization
Dentine
• application of non-collagenous proteins (NCP) analogues
and bioactive materials for the biomimetic mineralization of dentin
• However, it's hard to mimic in vivo conditions of complex oral

environment during experiment.
Cao C. 2015
BIOMIMETIC ENDODONTICS
AND
REGENERATIVE ASPECTS
1. Endodontic Irrigants
2. Intra-canal Medicaments
3. Biomimetic Endodontic Cements
• antimicrobial property
Endodontic
• without harming the healthy tissues and stem cells

Irrigants

• dissolve pulp remnants and necrotic tissues

• remove smear layer → may alter dentinal surface in the
root canal
Dioguardi M. 2018
Scott II 2018
Yu C. 2007
• Commonly used : sodium hypochlorite (NaOCl)

Endodontic hydrogen peroxide (H2O2)
chlorhexidine (CHX)
Irrigants ethylene diamine tetraacetic acid (EDTA)
saline
• chemical irrigants + intra-canal medicaments

Irrigant Main Outcome Reference

CHX (2%) No survival of SCAPs Trevino E.G. 2011
Endodontic Toxicity to SCAPs Wifbiller M. 2019
Irrigants
NaOCl (1.5%) Survival of SCPAs Martin D.E. 2014
EDTA (17%) Survival of SCPAs Trevino E.G. 2011

Martin D.E. 2014
• eliminate the residual microorganisms following

Intra-canal cleaning and irrigating
Medicaments

• prevents regrowth of microorganisms in the empty
pulp space
Bansal R. 2014
Hedge J. 2009
Ruparel N.B. 2012
- Calcium Hydroxide
Calcium Hydroxide - Triple Antibiotic Paste

- Bioceramics
• alkaline (pH ~12.5) white odorless compound
• acts on the bacterial cells to denatures their proteins by disrupting the cytoplasmic
membrane
• induces remineralization, repair/regeneration of dentin and inhibits resorptive activity
• prolonged time during the apexification : may weaken the root dentin by resorptive activity
and even fracture of the root
Mohammadi Z. 2011
Kaval M.E. 2018
Bakkal M. 2018
Lin J. 2017
- Calcium Hydroxide
Calcium Hydroxide - Triple Antibiotic Paste

- Bioceramics
• alkalinity of Ca(OH)2 → free hydroxyl ions (OH)

• Deep penetration of OH into dentinal tubules → raise pH and solubilize organic matrix
• Concentrations up to 500 mg/mL is conducive to survival of SCAPs

• Concerns
• Prolonged time should be avoided
• Incomplete removal of Ca(OH)2 from root canals
Shetty S. 2017
Althumairy R.I. 2014
Nerness A. 2016
- Calcium Hydroxide
Triple Antibiotic Paste - Triple Antibiotic Paste

- Bioceramics
• three antimicrobial agents including

bacteriostatic (minocycline) and bactericidal (metronidazole, ciprofloxacin)
• target the complete eradication of microorganisms from the root canals
Sideridou I. 2003
- Calcium Hydroxide

- Bioceramics
Ciprofloxacin (belongs to fluoroquinones)

• good penetration, highly effective against anaerobes present in necrotic pulp
• not very effective against the Gram-positive bacteria
Metronidazole
• against the obligate anaerobes originating from the necrotic pulp
Minocycline (derivative of tetracycline)

• interfere with the bacterial protein synthesis
Adefurin A. 2011
Ramu C. 2012
Windlet III. 2005
Ahmed N. 2013
- Calcium Hydroxide

- Bioceramics
• Concentration of 1mg/mL (1:1:1)

• elimination of root canal microorganisms up to 99.99%
• promotion of revascularization in immature permanent tooth
• Due to acidic pH, TAP demineralized the dentin surface

→ surface roughness of dentin → facilitates stem cells
differentiation and attachment
Krittika R. 2017
Ivica A. 2019
Alyas S.M. 2016
Latham J. 2016
- Calcium Hydroxide

- Bioceramics
• Concentration :
• 1mg/mL or lower : no unfavorable effect on the stem cell viability
• higher than 1mg/mL : detrimental effects on dental stem cells
Concern
• tooth-staining due the presence of minocycline is common
Krittika R. 2017
Ivica A. 2019
Alyas S.M. 2016
Latham J. 2016
Biomimetic Endodontic Cements

Bioceramics - Bioceramics
Bioactive bioceramics
• bioresorbable (CaP bone substitutes)
• non-bioresorbable (calcium silicate or hydraulic cements)
• induces a favorable response from host tissues

• deposition of HA layer when exposed to calcium and phosphate enriched tissue fluid
• good biocompatibility
• osteoconductivity
• osteoinductivity
• sealing ability
Brave A.D. 2012

Koch K. 2009
Skallevold H.E. 2019
Gray mineral trioxide aggregate (GMTA)

ProRoot mineral trioxide aggregate (MTA) (GMTA; Dentsply Endodontics, Tulsa, OK, USA)

• contains bismuth oxide, tricalcium and dicalcium silicates
• discoloration of teeth
Camilleri J. 2005
Perez A. 2003
Song J. 2006
Bodrumlu E. 2008
White MTA ProRoot(white mineral trioxide aggregate (WMTA)); Dentsply Endodontics, Tulsa, OK,

USA)
• lack of tetracalcium aluminoferrite
Camilleri J. 2005
Perez A. 2003
Song J. 2006
Bodrumlu E. 2008
• Drawbacks : cost, wash out during irrigation, delayed

setting and difficult manipulation
Despite MTA is the gold standard for root-end restorations
Camilleri J. 2005
Perez A. 2003
Song J. 2006
Bodrumlu E. 2008
Biodentine (Septodont, Saint Maur des Fosse´s, France)

• contain zirconia, tricalcium silicate and radio-opacifier which
interacts with the living cells and have proven good biocompatibility
• overcome major concerns of MTA (such as discoloration) and can be

preferred in anterior teeth
Gomes-Filho J.E. 2009

Laurent P. 2008
Bezgin T. 2015
Mullaguri H. 2016
Valles M. 2015
 Mechanical
 Aesthetic
BIOMIMETIC
TISSUE-ENGINEERING
ASPECTS
Biomimetic Tissue-Engineering
3. Growth factors:
support cell functions
1. Scaffold:
Facilitates cells differentiation,
proliferation and biosynthesis
2. Cells:

1.Biomimetic Scaffolds: Desired Properties
- biocompatible
- mimic physical & mechanical properties
mimic extracellular matrix - high porosity
- bioactivity
- bioresorbable & biodegradable rate

1.Biomimetic Scaffolds: Material  Polymers,
• natural polymers
• synthetic polymers
Collagen
- main benefit is enzymatic biodegradation and mechanical properties
- can be altered with inorganic compounds, e.g., H, chitosan, gelatin.
- mouse calvarial defect was implanted by collagen–HA

scaffold derived from mesenchymal stem cells of mouse-
bone marrow.
-The defect was healed after 3 weeks.
Others: Chitosan, Platelet-rich fibrin

1.Biomimetic Scaffolds: Material  Polymers
• natural polymers
• synthetic polymers
- longer shelf life and cost effectively.

- better mechanical and physical properties.
- but less ability to interact with cells and biocompatibility issues.
- Solution is to fabricate composite scaffolds.
- Ex. Hydrogel, polypropylene fumarate (PPF), polylactic acid (PLA)

1.Biomimetic Scaffolds: Material
 Polymers, Bioceramics
Calcium phosphate (CaP)
- widely used in the regeneration of hard tissues

- biocompatibility, good bioactivity, osteoinductivity, and osteoconductivity.
- but poor mechanical properties, and difficulty of shaping
- limit their wide application in tissue engineering.

1.Biomimetic Scaffolds: Material
 Polymers, Bioceramics, Metal
- Recently, degradable metallic biomaterials known as “biodegradable metals” (BMs)

- gradual corrosion that releases corrosion products which elicited appropriate host response
- Examples of BMs include Iron (Fe), calcium(Ca), magnesium (Mg)
- lack of data regarding biocompatibility and cell viability the potential of these materials is currently
uncertain

1.Biomimetic Scaffolds: Method of processing 3D biomimetic scaffold
1. Porogens in biomaterials
for example, particulate-leaching, freeze-drying
2. Rapid prototyping techniques including 3D Printing

(3DP), Bioprinting (3D plotting or direct-writing)

1.Biomimetic Scaffolds: Method of processing 3D biomimetic scaffold
3. Woven or non-woven fibers scaffolds using electrospinning and microsphere sintering

2. Dental stem cell therapy for biomimetic tissue regeneration
• Stem cells are undifferentiated, capable of cell differentiation and self-renewal
• Adult stem cells are referred as multipotent mesenchymal stromal cells (MSCs)
• There are various types and sources of post-natal dental stem cells.

3. Biological signaling growth factors
- complex system of communicate interactions within the cell and directs different cell activities
- major role in regulation of tissue differentiation

Bone morphogenetic proteins(BMP):
- cytological differentiation of pulp cells into pre-odontoblasts and odontoblasts.

3. Biological signaling growth factors
Fibroblast growth factor (FGF)

- induce angiogenesis, chemotaxis and cell proliferation of periodontal ligament cells
Transforming growth factor (TGF)

- major role of TGF-β in tissue homeostasis, osteo/chondrogenesis, tissue repair
- TGF-β inhibits proliferation of macrophages and neutrophils

Tooth bioengineering and regenerative dentistry
1. Embryonic tooth bud-based

strategies
2. Postnatal dental cell
3. Current challenges
Yelick PC. 2019

1.Embryonic tooth bud-based strategies for tooth regeneration
• Embryonic tooth formation: inductive signal
Oral ectoderm underlying mesenchyme dental epithelium
• Bioengineered tooth-based developmental signaling cascades

- Inductive signal from nondental source: bone marrow
- Induce tooth formation in epithelial cells isolated from gingiva
combined embryonic tooth mesenchyme
- constructs in a renal capsule mouse
Yelick PC. 2019

2. Postnatal dental cell for bioengineered whole-tooth tissue engineering
- the regenerative capacity of adult dental cells for applications in bioengineered replacement tooth
formation
- Adult dental stem cells harvested from deciduous or adult exfoliated teeth are ideal sources for
applications in tooth regeneration because they are readily available, can be harvested and banked for
future use.
- the first to characterize a clonogenic and rapidly proliferative population of cells harvested from adult
human dental pulp, called dental pulp stem cells (DPSCs).
Yelick PC. 2019

 Stem Cells from Human Exfoliated Deciduous Teeth
(SHED)
- SHED are highly proliferative and capable of differentiation

- When implanted in vivo, SHED formed bone and dentin
• Another group: harvested from unerupted porcine tooth buds
• culture and seeded onto available biodegradable scaffolds such as polyglycolic acid (PGA)
• this approach could be used to generate small, anatomically correct tooth crowns,
consisting of dental pulp, dentin, and enamel
Young. 2002
 Induced Pluripotent Stem Cells (iPSCs) for Dental Tissue Regeneration
• iPSCs: The potential to create any type of autologous cell from cells easily and painlessly
obtained from any individual
• Efforts are ongoing to regenerate dental pulp (Goldberg 2011),

periodontal ligaments (Cho et al. 2019), odontoblasts(Xie et al. 2018),
and ameloblasts(Abdullah et al. 2019)
Yelick PC. 2019

 Scaffold Materials for Whole-Tooth Tissue Engineering
• hydrogel scaffolds such as gelatin methacrylate (GelMA) hydrogels ,

and natural decellularized tooth bud scaffolds
adult dental cell sources and decellularized natural

tooth bud extracellular matrix (ECM) scaffolds,
close to full-sized teeth have been bioengineered
and grown in the jaws of mini pig hosts,
Yelick PC. 2019

3.Current challenges for whole-tooth tissue engineering
• Full-Sized Bioengineered Teeth of Predetermined Size and Shape?
• Proper vascularization and innervation?
• Fighting infection and maintaining oral health?
• Cost and dental insurance considerations?
Yelick PC. 2019

 Mechanical
 Aesthetic
BIOMIMETIC
MINERALIZATION
Dental caries
Featherstone, 2008
Nuii et al., 2014
REMINERALIZATION
IN ENAMEL
Pandya et al., 2018
Pandya et al., 2018
Pandya et al., 2018
Pandya et al., 2018
Synthesis
generation
1st fluoride fluorapatite / fluorhydroxyapatites
full- length recombinant fluoridated calcium phosphate coat with

2nd pig amelogenin rP172
with fluoride needle-like crystal
3rd amelogenin fragment promote enamel crystal nucleation and growth
polyamidoamine dendrimer self-assembling potential and an ability to induce

4th crystal remineralization in c-axis direction in vivo has
(PAMAM-PO3H2) been generated
Pandya et al., 2018

Pandya et al., 2018
Pandya et al., 2018
Buzalaf et al., 2011
Buzalaf et al., 2011
Golpayegani et al., 2012
Khijmatgar et al., 2020
Golpayegani et al., 2012
Khijmatgar et al., 2020
Thierens et al., 2011
Hannig et al., 2010
Hannig et al., 2010
Juntavee et al., 2021
Geeta et al., 2019
Bossù et al., 2019
Bossù et al., 2019
Bossù et al., 2019
Joshi et al., 2019
Joshi et al., 2019
REMINERALIZATION
IN DENTIN
Nuii et al., 2014
Nuii et al., 2014
Nuii et al., 2014
Nuii et al., 2014
Nuii et al., 2014
Nuii et al., 2014
BIOMIMETIC RESTORATIVE
Adhesive dentistry
Field of fixed prosthesis

• Principles of preparation Biomimetic approach
• Mechanical retention • Maximum preservaton
Paradigm shift • Minimally invasive
• Reparable
Magne P & Schlichting LH, 2016

Biotelle P et al, 2019
Restorative dentistry
Adhesive CAD/CAM Biomimetic
• IDS • Precise & quality • Study to design &

• Non retentive • User friendly engineer materials
• Minimal invasive • Chairside • Structure, function,
• Polymer & ceramic biology, esthi

Conservative & reparable
Biomimetic Vitality & function
Stem cell Natural tooth Materials

• Entire Tooth
• Partial

CASE REPORT
Concept of adding material to
Additive dentistry eroded teeth
• Impression
• waxing
Alternative choice – need further study
Endodontically treated tooth (ETT)
• Higher incidence of fracture compared to vital tooth due to
• Previous caries – large, deep
• Fracture of coronal structure
• Access for RCT
• Structural integrity decrease, flexibility increase
• Cuspal deflection during the function
• The preservation of tooth structure of endodontically
treated teeth is paramount  higher fractur resistance 
higher survival rate
Preserving coronal structure
• Fracture resistance
• PFM crown with Coronal structure < 50%  fail more
• 1.5-2 mm ferrule has positive effect to fracture resistance
• Improvement in adhesive  partial coverage restoration as an
alternative
• More preservative- prevent tooth structure loss
• Coverage and protect weakened cusps
• Eliminate need for axial wall destruction
Survival
Survival rateofofrestoration
rate tooth
Failure mode of restoration
Catastrophic Reparable
• Complicated Fracture • Fracture of restoration
• extraction • Uncomplicated fracture
• Dislodgement
Fail
survive
Types of post
Fiber post
Cast post
• High fracture resistance • Similar
ic f a ilu re modulus
elastic
r op h
Si milar e of C a ta s t
• Stress concentration & transmission
n c id e n c s
• Stress distribution
ra te
• I su cc e s
• High risk of root fracture Survi v a l & • Low risk of root fracture
•
• Catastrophic failure – unreparable • Favorable failure
Postless approach – less incidence of

Failure mode – chance of repair
catastrophic failure
Postless approach
• Postless build up c crown
• sufficient inter-arch space and tooth structure
• Endocrown
• insuffiecient interarch space
• Gain retention from pulp chamber
• Simple and less invasive
• Time & cost
• Short term Success rate 94-100%
• Quality & quantity of adhesive
• Bond btw restoration & underlying tooth structure
• Immediate dentin sealing
Discussion
Improvement of adhesive  use of post
Partial coverage more preserve
the remaining tooth structures

Main factor that affect the success of ETT Not the strongest restoration
Restorative procedure  most conservative & reparable

CONCLUSION
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BIOMIMETIC

Sohail Zafar m. 2020

Sohail Zafar m. 2020

Sohail Zafar m. 2020

Sohail Zafar m. 2020

Sohail Zafar m. 2020

Sohail Zafar m. 2020

• The direct restorations with FRC material comprise 2 layers

The fibers in everX Posterior increase the adhesion to overlying

Limiting the thickness of

• structurally (short fibers resembling the collagen network in dentin)

Absorb and distribute the occlusal stress

Ideally, a restorative dental material or

Chemical/light-cured RDCs and GIC:

• However, it's hard to mimic in vivo conditions of complex oral

• without harming the healthy tissues and stem cells

• dissolve pulp remnants and necrotic tissues

• Commonly used : sodium hypochlorite (NaOCl)

• chemical irrigants + intra-canal medicaments

Irrigant Main Outcome Reference

Endodontic Toxicity to SCAPs Wifbiller M. 2019

EDTA (17%) Survival of SCPAs Trevino E.G. 2011

• eliminate the residual microorganisms following

Calcium Hydroxide - Triple Antibiotic Paste

• alkaline (pH ~12.5) white odorless compound

• induces remineralization, repair/regeneration of dentin and inhibits resorptive activity

Calcium Hydroxide - Triple Antibiotic Paste

• alkalinity of Ca(OH)2 → free hydroxyl ions (OH)

• Concentrations up to 500 mg/mL is conducive to survival of SCAPs

Triple Antibiotic Paste - Triple Antibiotic Paste

• three antimicrobial agents including

• target the complete eradication of microorganisms from the root canals

Triple Antibiotic Paste - Triple Antibiotic Paste

Ciprofloxacin (belongs to fluoroquinones)

Minocycline (derivative of tetracycline)

Triple Antibiotic Paste - Triple Antibiotic Paste

• Concentration of 1mg/mL (1:1:1)

• Due to acidic pH, TAP demineralized the dentin surface

Triple Antibiotic Paste - Triple Antibiotic Paste

Biomimetic Endodontic Cements

• induces a favorable response from host tissues

Brave A.D. 2012

Gray mineral trioxide aggregate (GMTA)

• contains bismuth oxide, tricalcium and dicalcium silicates

White MTA ProRoot(white mineral trioxide aggregate (WMTA)); Dentsply Endodontics, Tulsa, OK,

• Drawbacks : cost, wash out during irrigation, delayed

Despite MTA is the gold standard for root-end restorations

Biodentine (Septodont, Saint Maur des Fosse´s, France)

• overcome major concerns of MTA (such as discoloration) and can be

Gomes-Filho J.E. 2009

Sohail Zafar m. 2020

Sohail Zafar m. 2020

- mouse calvarial defect was implanted by collagen–HA

Others: Chitosan, Platelet-rich fibrin

- longer shelf life and cost effectively.

Sohail Zafar m. 2020

Calcium phosphate (CaP)

- widely used in the regeneration of hard tissues

2. Rapid prototyping techniques including 3D Printing