Tissue Engineering and Regeneration



What is Tissue Engineering?

Tissue Engineering is the science of manipulating cells to regenerate tissues, replacing damaged, diseased or missing tissues and even organs, Although a relatively new technology, it has had significant success in the regeneration of skin bone and cartilage.

Tissue Engineering:-

  • Enables control of the body’s natural healing and regeneration processes using:-


  •     - grafts
        - membranes
        - growth factors


  • Promotes enhanced healing  and regeneration of bone and soft tissue

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  • Guides the growth of soft tissue in the reconstruction of defects
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  • Guides the growth of bone in the reconstruction of defects
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  • May be used in conjunction with titanium implants
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    Stem Cells

    More recently, exciting advances in Tissue Engineering have been made in the creation of new organs (organogenesis) using Stem Cells. Stem cells are undifferentiated - i.e. they have the potential to develop into any cell line and develop into any organ, if given the correct signals. In the orofacial region, research conducted in Kings College London by Professor Paul Sharpe www.odontis.co.uk has demonstrated that the molecular control of tooth development is possible by the manipulation of homeobox genes* which control tooth initiation and dental patterning. This pioneering research work heralds clinicial studies in the regeneration of human teeth and natural live tooth replacement by Tissue Engineering.

    *a characterisitc DNA segment found in the genes of all higher organisms from the frutifly to humans



    Graft material - slowly incorporated into new bone

  • non biological allografts (e.g. bioactive glass)


  • sterilised bone grafts (e.g. bovine bone xenografts)


  • bone bank allografts (e.g. human demineralised bone matrix)


  • autologous bone grafts (e.g. same patient donor hip / skull / rib)





  • Collagen Membranes

    Resorbable collagen or polylactate membranes may be tacked in place to secure graft material. The use of membranes permits controlled guided bone and tissue regeneration to create:-

  • protective barriers (prevention of unwanted ingrowth of soft tissue into graft)


  • scaffold for epithelial migration (for closure of defects)





  • Collagen Membrane



    Tissue Engineering - Maxillary Atrophy

    We have been able to demonstrate successful regeneration of the upper jaw using Engineering Assisted Surgery™ techniques.

    The wasted upper jaw (Maxillary Atrophy) occurs in patients following an upper dental clearance, and historically has been an extremely difficult problem to solve, often involving major surgery, not without risk for many patients.

    Patients with Maxillary Atrophy have a significant disability which significantly impares the quality of life. Upper dentures become extremely loose to the extent that they cannot be worn - not even with the use of denture fixative. The condition may be initiated by the rocking motion of an upper denture in a patient with missing lower posterior teeth, and who does not wear a occlusion balancing lower denture. This rocking motion is produced by the lower anterior incisor teeth, which bite only into the front upper denture. The underlying bone cannot withstand this trauma - and disappears.

    The management of this condition has been revolutionised by Engineering Assisted Surgery™ techniques and by Tissue Engineering in particular. Safer treatment options are now possible without recourse to major surgery - or even hospitalisation - as an outpatient procedure in the dental surgery, under local anaesthesia.

    Following upper jaw regeneration, upper dentures can be made and stabilised with dental implants, without palatal cover, greatly enhancing the quality of life for patients. A stabilised denture is known as an Overdenture.

    Lower overdentures can be very comfortable and effectively stabilised using an inexpensive Mini Dental Implant System. Many patients state that these overdenture solutions produce result which feel as is they have been given back their own teeth.

    The cost of this treatment modality is very much reduced, making these treatment options more accessable for patients.

     

    Case 1

  • 20 year history of inability to wear upper denture


  • The upper jaw has disappeared (maxillary atrophy)





  • Computer Planning


    Treatment Plan Guided Bone Regeneration

  • Bio-Oss and Demineralised Bone Matrix graft material


  • Graft mixed with Platelet Rich Plasma (rich in growth factors)


  • Graft areas covered by collagen membranes


  • Procedures


  • - Bilateral Maxillary Sinus Lifts (red)

    - Bilateral Nasal Floor Lifts (blue)

    - Alveolar augmentation (yellow) to increase width and height of jaw

    - Denture stabilisation with Mini Dental Implants (MDI Sendax) http://www.imtec.com



    Platelet Rich Plasma - Blood Clot and Growth Factors

     

    Platelets are rich in:

    • chemical messengers
    • growth factors



    These factors increase:

  • Cell division (mitosis)


  • The migration of cells (chemotaxis) associated with healing


  • The differentiation of cells associated with tissue formation and wound healing




  • Platelet Rich Plasma (PRP)



    • Promotes enhanced healing and regeneration of bone and soft tissue
    • Guides the growth of soft tissue in the reconstruction of  defects
    • Guides the growth of bone in the reconstruction of defect
    • 15-30% increase in bone trabecular density
    • acceleration of bone maturation by 2 months
    • earlier placement of implants possible



      Surgery

           

           


  • Surgery was carried out under local anaesthesia in a NCAFOS dental surgery under local anaesthesia.


  • Intravenous sedation is an option but was not required in this case.


  • Bone grafts were mixed with platelet rich plasma.


  • Grafts were covered with collagen membranes to prevent the unwanted ingress of soft tissue into the grafted area.


  • In this case an additional biological membrane was created using platelet poor plasma.


  • Surgery time 1 hour.


  • This technique obviates the need for hospital admission and major surgery and is a major advance.




  • Transitional Stabilisation

         


    Transitional stabilisation was achieved at 3 weeks following grafting with a single Mini Dental Implant placed in the anterior nasal spine.

    This implant became loose but still maintained its function of excellent stabilisation of the upper denture for a period of 6 months.


    Transitional Stabilisation (6months)


    OPT Radiograph 6 months

    Radiographs show that the implant has lost its attachment to bone, but the clinical image shows that the implant although submerged is still functioning without any evidence of peri-implantitis.

     

    Transitional Stabilisation at 6 months


    Denture Conversion and Stabilisation @ 6 months

    Long 18 mm inexpensive Mini Dental Implants were placed in the grafted area and denture stabilisation was achieved without recourse to major surgery, with excellent retention of an upper denture.

    Over a 6 month period several Mini Dental Implants were lost and were simply replaced without significant increase in cost.

     


    Outcome - 6 months

    Lower Dental Clearance and Provision of New Dentures

    A lower clearance was carried out at 6 months with stabilisation of an immediate lower denture.

    The upper denture was made without palatal cover.

    Note the facial rejuvenation achieved with the overdenture technique.

    This has been achieved without recourse to soft tissue enhancement of any kind, and illustrates the importance of the teeth and jaws and lip support achieved by the overdenture in the generation of facial harmony.

    There is....

    • improvement in muscle tone
    • better exposure of the upper incisor teeth
    • filling out of the nasolabial folds.

    This outcome would not have been possible with single tooth implant treatment plan unless combined with major jaw advancement osteotomy surgery, which still would have provided an inferior rejuvenation effect.

     

    Outcome - 5 months post clearance

     

    Outcome @ 2 years

    Outcome @ 2 years confirms osseointegration of 4/7 MDI implants in the maxilla. Two implants in the anterior maxilla and one implant in the region of the right premolar (bicuspid) are mobile. Two of the loose implants appear to be tissue integrated - i.e. adherant to soft tissue to the effect that the implants are functioning, and are assisting in a superb retention of the upper palateless denture.

    This is an important observation and may have importance in the creation of a tissue integrated system which may function in the absence of bone. Loose implants remain under close review and may be augmented with bicon implants as a two staged technique.

     

    2 year Outcome - Palateless Upper Denture

     

    Mandibular Implants

    (despite gingival recession all implants are osseointegrated and functioning)

     

    Outcome: Excellent Retention @ 2 years

    Click Image for Patient Comment

    wmv file 164 KB

     

     

    Overdenture Retention

    wmv file 164 KB

    Case 2

     

    Computer Planning

     

    A case of severe maxillary atrophy treated with the same method of grafting as Case 1.

    The patient decided to undergo treatment of the maxilla only.

    No hospitalisation was required.

    An initial plan using Mini Dental Implants was converted to bicon implants http://www.bicon.com following loss of implants (see below).

    Bone density was assessed and bicon Implant placement was planned using Simplant 9 software.

     

     

    Grafted Maxilla

    Computer Planning - Simplant 9

    http://www.materialise.com/simplant/main1_ENG.htm

     

    Bicon Implants

    Bicon Implant Placement - Virtual Reality

    Simplant 9 Computer Planning

    Bone Density in Grafted Maxilla

     

    Grafted Bone and Misch Grading of Bone Denisty

    • D1 (dark grey) at the apex of the implant (very dense bone)
    • D2 (blue) in the apical third of the implant (dense bone)
    • D3 (green) in the mid third of the implant (almost extending into D2)
    • Platelet rich plasma moves bone denisty up by one Misch Grading e.g. from D3 - D2

     

    Outcome

     

    Click Image for Patient Comment

    wmv file 170 KB

     

    Overdenture Retention

    wmv file 101 KB

     

     

     

    Discussion

    The use of Engineering Assisted Surgery™ techniques in association with Tissue Engineering and the use of Mini Dental Implants secured a successful outcome possible in Case 1, without the need for major surgery, general anaesthesia nor hospitalisation.

    In Case 2 initial placement of Mini Dental Implants initially provided excellent retention and were replaced with bicon implants as a two-staged procedure. This resulted in a successful outcome.

    It is interesting to note in Case 2 that one of the Mini Dental Implants fractured in dense bone. This implies that osseointegration occurred and that the fracture was related to loading of the implant in dense bone graft with possible compromised elasticity.

    Key Points:

    • EAS Technology has converted two very difficult case into comparatively easy cases
    • Minimal Surgery under local anaesthesia
    • Single Site Surgery (no second surgery site for donor bone graft)
    • No Hospitalisation
    • Early rehabilitation
    • Low Risk - Overdenture option easier to salvage than individual tooth replacement
    • Low Cost
    • Excellent Outcome - Superior Dental Aesthetics (Gum line) with denture flange
    • Excellent Outcome - Superior Facial Rejuvenation with Overdenture option
    • Individual tooth replacement with dental implants - poor gum aesthetics and little rejuveneation without major jaw advancement surgery


    Patient Outcomes


    In Case 1 this technology has “given the patient back her life”

    In Case 2, a complete inability to retain an upper denture has been solved.

    These outstanding outcomes are life changing events, that are now possible without recourse to major surgery.

    Dental Prosthetics: Ben Swindell of Crown Ceramics, Ripley, Derbyshire.

    The author wishes to acknowledge the input of all colleagues working in this area, whose input has made this kind of surgery possible - particularly Professor Robert Marx in the field of Tissue Engineering and Platelet Rich Plasma research, Dr. Victor Sendax, who developed the MDI Sendax Mini Dental Implant System and Thomas Driskell the innovator of the Bicon Dental Implant System, which has been extensively clinically investigated by Dr Vin Morgan.

    Their contribution to the solution of these problems has been crucial.