Bone tissue engineering challenges in oral and maxillofacial surgery

Bone Tissue Engineering challenges

in Oral & Maxillofacial Surgery

Presenter : S.Mohammad Zargar

Supervised by Dr. Nima Jamshidi

Fall 2016

Contents

• Overview of Maxillofacial Defects

• Current Methods of Reconstruction– Mandible Reconstruction

• Tissue Engineering approach• Scaffold

• Cell

• GF

• Future Challenges

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Overview of Maxillofacial Defect

• The loss or dysfunction of skeletal tissue that can accompany

trauma, injury or disease

• Result in significant morbidity as well as a variety of socio-

economic issues

• What are craniofacial anomalies?– Craniofacial anomalies (CFA) are a diverse group of

deformities in the growth of the head and facial bones.

– They are Congenital.

– Causes:

• Combination of genes

• Environmental

• Folic acid deficiency

– Like:

• Cleft lip and/or cleft palate

• Craniosynostosis

• Hemifacial macrosomia

• Trauma3

Current Methods of Maxillofacial

Reconstruction

• A variety of reconstructions are practiced and are a reflection

of experience, and resources available to the treating

surgeon.

• Categorization

– Non-vascularized Reconstruction

– Vascularized Reconstruction

The defining feature between the two is the presence of a

blood supply for the transplanted tissue at the time of

placement.

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• The ideal reconstruction will be defined by the

characteristics of the defect to be restored.

– Patient factors such as overall health and viability of donor sites

• The inciting cause of the defect

– Traumatic defects

– The treatment of pathology

• Benign

• Malignant

• Prior surgery can make subsequent surgical therapy difficult.

• Radiation

– The effects of radiation-induced fibrosis on soft and hard tissue

– Sclerosis of blood vessels that can compromise the ability to

consider a microvascular reconstruction

• Chemotherapy

Current Methods of Maxillofacial

Reconstruction

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Mandible Reconstruction

• The mandible is a unique structure of the head and neck

– multiple functions

• A significant component of the structure of the face

• An arch-shaped bone that supports the lower dentition

• Mastication

• Speech

• Defects in the mandibular region may be isolated to

– bone

– soft tissue

– composite defects

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– Common Sources:

• Autogenous origin– Anterior and Posterior iliac crest (P>A)

– Tibial plateau

– Rib

– calvarium

• Allogenic origin– For small defects

– In conjunction with autogenous graft


The ideal bone graft should be osteogenic, osteoconductive

and osteoinductive.

Components within cortical bone such as bone morphogenic protein

(BMP) exhibit osteoinductive properties to facilitate bone growth in non-

vascularized grafts.

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• Success Rate depends on:

– The vascularity of the recipient site

– The quantity of osteoblasts present in the graft material or through

recruitment by mediators such as BMP.

– Length of the bony reconstruction (83% in <6cm and 25% in >12cm)

– Salivary contamination (graft failure rate of at least 50 %)

• The success rate approaches 100 % when reconstruction is

delayed and an extraoral approach is utilized to avoid oral cavity

contamination.


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Exp. Titanium reconstruction plate

– To secure vascularized and non-vascularized bone grafts to

the defect site

– Failure Rate:• In Anterior mandible defect reconstruction: FR=52%

• In lateral mandible defect reconstruction: FR=7.7-12.5%


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– not dependent on adjacent tissue for success

• Sources:

– The fibula osteocutaneous free flap• Good length and quality of bone

• Concurrent harvest of adjacent tissue types Like

muscle, skin and fascia


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– Scapula flap• Advantageous due to multiple skin paddles

• limited by the size and volume of bone available

• Insufficient in bone thickness

• Difficulty in simultaneous harvest with recipient site

preparation due to patient positioning in lateral decubitus

– The Deep Circumflex Iliac Artery flap (DCIA)• Excellent quality and quantity of bone for reconstruction


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Current Methods of Mandible

Reconstruction

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Pre-surgical planning

• Preoperative imaging in the form of CT angiogram, MR

angiogram, or Doppler ultrasound is commonly

performed to ensure there exists adequate vessels that supply

the foot

• Recent advances in

virtual pre-surgical

planning have allowed

surgeons to collaborate

with engineers in

designing surgical

guides.

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Tissue Engineering (TE)

• Current approaches to replace or restore significant

quantities of lost skeletal tissue come with substantial

limitations and inherent disadvantages that may be

harmful.

• Tissue engineering and regenerative medicinehave come to the fore in recent years with new

approaches for de novo skeletal tissue formation in an

attempt to address the unmet need for bone augmentation

and skeletal repair.

• These approaches seek to harness stem cells,

innovative scaffolds and biological factors to create,

ideally, robust, reproducible and enhanced bone formation

strategies to improve the quality of life for an ageing

population.

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Scaffold

• Ideal Scaffold:

– Mimic the natural biomechanical properties of host tissues• A complex mixture of bone, skin, muscle, cartilage, adipose tissue and other support

tissues.

– Osteoconductive: promote bone cells to adhere, proliferate

and generate their natural extracellular matrix.

– Osteoinductive: stimulate the bone healing process by

recruiting immature cells and facilitating the differentiation of

preosteoblasts

– An Interconnected pore structure (pores >100 μm in

diameter)

– Biodegradable

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Scaffold

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Scaffold

• Scaffold Material– A critical factor in the success of the device

– Encourages cellular regrowth

• Categorization:

– Bioceramics• CaP-based Bioactive Ceramics

– High Osteoconductivity and Bone regenerative capacity

– Injectable CaP cements

– Degradation is limited

» Creation of macropores

– Brittle

– Biopolymers• Natural (Collagen, Gelatin and Hyaluronic acid)

– Enzymatic degradation (Exp. Collagenase)

• Synthetic (PGA, PLA,PCL and PLGA)

– Biocompatible

– Biodegradable

– Degraded by Simple Hydrolysis

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Stem Cells

• An optimal stem cell source

– No immunorejection

– No graft-versus-host disease

– No tumorigenicity

– Immediate availability

– Availability in pertinent quantities

– Controlled cell proliferation rate

– Predictable and consistent osteogenic potential as well as

controlled integration into the surrounding tissues.

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Stem Cells

• Autologous sources are most

desirable – eliminating complications associated with

immune rejection of allogenic tissue

• Bone marrow

• Mesenchymal Stem Cell (MSCs)o MSCs can differentiate into bone, cartilage,

adipose tissue and hematopoietic-

supportive stroma cells

o Osteogenic potential

o Easy isolation

o High proliferative potential

o Freezing conditions do not affect the

osteogenic potential of MSCs

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Bioactive Factors

• For craniofacial bone regeneration, there must be

cellular growth, differentiation and

proliferation. These processes are highly

regulated by the cell and must be initiated by

specific bioactive molecules.

• Growth factors communicate cell signals:

– Bone morphogenetic protein (BMP)

• Stimulate mesenchymal stem cells to

differentiate towards an osteoblastic phenotype

– Platelet Derived Growth Factor (PDGF)

• Increasing DNA synthesis and mitosis activity

and collagen synthesis in osteoblasts

– Transforming Growth factor-Beta (TGF-ᵦ)

• Modulating bone cell metabolism and including

neovascularization

– Fibroblast Growth Factor (FGF)

– Insulin-Like Growth Factor (IGF)

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Future challenges

• Over the past two decades there has been a substantial amount of

progress in TE.

• Recent advances in TE strategies and techniques have

demonstrated an increased efficacy.

• How a suitable population of cells can be identified and

harvested that fulfill the physiological role of the native

tissue?

• How exogenously or endogenously supplied Growth Factors

can best support cellular differentiation and reproduction?

• The role the microvasculature plays in tissue regeneration?

• As our ability to simulate physiological microenvironment

increase, it is essential that our understanding of adverse

events, such as infection, must improve.

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Thanks for Your Patience

S. Mohammad Zargar

The future of craniofacial TEdepends on the ability of theclinicians and the engineers tocommunicate together.