Periodontal Regeneration Flashcards
New attachment
New attachment involves the embedding of new PDL fibers into new cementum and attachment of the gingival epithelium to a tooth surface previously denuded by disease
Reattachment
Reattachment is the reunion of epithelial and connective tissue with a root surface and refers to repair in areas of the root not previously exposed to the pocket such as after surgical detachment of tissues, traumatic tears of cementum, tooth fractures
Bone fill
Does not address presence or absence of new cementum, PDL, or alveolar bone histologically!
Refers to clinical assessment (Probe resistance and radiodensity)
Biodegradable vs Bioresorbable vs Bioabsorbable
Biodegradable refers to degrading WITHOUT PROOF OF ELIMINATION
Bioresorbable refers to degradation with ELIMINATION THROUGH NATURAL PATHWAYS (metabolism)
Bioabsorbable refers to DISSOLVING in body fluids with no enzymatic degredation required
What is GTR?
a surgical procedure with the goal of gaining new bone, cementum, and PDL attachment to a periodontally diseased tooth with the use of barrier membranes.
Karring et al. 1980a and b
No barrier used - gingival contact caused resorption - No CT attachment (bone and gingiva fail to induce CT attachment)
What was the first GTR in human?
Nyman et al. 1982b
Nyman et al. 1982a and b
used Milipore filter membrane
New cementum inserted collagen fibers at apical end
CT adhesion with no new cementum at coronal
Gottlow et al. 1984
Milipore filter VS Flap alone
Milipore filter had considerably more attachment
What functions do the barrier membrane provide?
Space Maintenance
Epithelial Exclusion
Wound Stabilization
How many cell types are competing for the healing space in GTR?
What are they?
5 Epithelial cells Connective Tissue Fibroblasts Alveolar bone cells PDL cells Cementoblasts
What happens to an exposed root surface when it is repopulated with different cell types?
Caffesse & Becker 1991
Epithelial: Long junctional epithelium
Connective tissue: root resorption
Osseous: ankylosis
PDL: regenerated attachment
Why is Nyman 1982 a landmark study for GTR?
Proof of new cementum formation with inserting collagen fibers 3mo after GTR
Showed concept of excluding soft tissue (CT and epi) to allow multipotent PDL stem cells to form new attachment
Wang & Boyapati 2006
PASS Principle for predictable GBR (GTR)
Primary wound closure
Angiogenesis
Space maintenance/creation
Stability of the wound
What do each principal of PASS provide?
Primary wound closure: facilitate tissue maturation
Angiogenesis: cells which release growth factors/cytokines/undifferentiated cells to repopulate
Space: bone graft/membranes/CAF/tenting screws - space for bone formation
Stability: necessary for wound healing/clot formation/barrier fixation
How many methods of regeneration are there? what are they?
5
Interdental denudation Coronally Advanced Flap Grafts GTR (Membrane) Biologic Agents
What biomaterials are used in GTR?
Membranes
Grafts
Biologic agents
What options are there for Non-Resorbable Membranes?
Cellulose Ester Millipore Filter ePTFE (Gore-Tex) dPTFE Titanium-reinforced ePTFE Titanium Mesh
What does e/dPTFE stand for
Expanded/Dense Polytetrafluoroethylene
Pore size of Cellulose Ester Millipore Filter
0.22µm
Pore sice for ePTFE
0.45µm
Pore size for dPTFE
0.2µm
For Non-resorbable membranes - why do we get a thin layer of soft tissue on the inside of the membrane?
Foreign body reaction
Micro-movement induced fibrous encapsulation
What characteristics are membranes made based on?
Biocompatibility Maintaining Vascularity Cell occlusion (Epi/CT) Tissue Integration Cell: Migration, Attachment, Proliferation, Differentiation at membrane substratum Bacterial resistance Space-making capability Clinical handeling
What function(s) to pours provide?
Tissue integration (mechanical support) Bacterial resistance (smaller pour size = less bacteria)
What classical study used an ePTFE membrane? Description/Results?
Dahlin et al. 1990
7 Monkeys - healing of Max and Mand bone defects
Bio-inert ePTFE with pour size too small for Epi/CT cells (but not bacteria***) created a secluded environment for osteogenesis to take place.
How many borders does an ePTFE membrane have? What are they and what do they do?
2
Coronal (clot formation, collagen fiber penetration, delay epi migration)
Occlusal (cell occlusion, space maintenance)
What is the downside of ePTFE? Citation
Larger pour size allows for bacterial invasion
Lang et al. 1994 found 30-40% membrane exposure associated bacterial infection
Name 2 studies that discuss impact of pore size in ePTFE
What do they say?
Larger pore size of ePTFE may allow bacteria to penetrate easier and be the reason for the greater infection rate vs dPTFE
Selvig et al. 1990
Lang et al. 1994 - 30-40% exposure associated infection
When should a Titanium-reinforced ePTFE be used? Citation
Wide and/or Non-supportive defects
Cortellini et al. 2000
When should Titanium Mesh be used
More for GBR
What studies investigated the effect of pore size on GTR?
Zellin & Lindhe 1996
Wikesjo et al. 2003
What study compared pore sizes in non-resorbable membranes?
Test 3 different pore sizes
20-25µm and 100µm group had increased rate of osteogenesis vs 8µm
(higher permeability and tissue integration)
Zellin & Lindhe 1996
Wikesjo et al. 2003
Tissue occlusion does not appear to be a critical determinant, but may be a requirement for GTR
What options are there for resorbable membranes?
Collagen-based
Polymer-based
Allografts (Acellular Dermal Matrix - Amnion-Chorion)
What is the main difference between Cross Linked and Non-Cross Linked Collagen Membranes?
Degradation time
How do collagen membranes degrade?
Host Collagenases
MMP1 (Fibroblasts)
MMP8 (Macrophages, PMNs, Neutrophils - Inflammatory)
MMP13 (Osteoclasts)
How are Cross Linked Collagen membranes, cross linked? What effect does it have?
Usually w/ Glutaraldehyde but can be ribose cross linked (OSSIX)
Glutaraldehyde is released during the degradation process, delaying epithelial cell migration - leading to slower degradation - more time for selective cell re-population - also increased inflammatory/foreign body response though
How long does it take for collagen membranes to resorb? Citation
3-4weeks (Paul et al. 1992)
Longer for cross-linked
What are the pros and cons of cross-linked collagen membranes? Citation
Pros: Longer resorption time leading to longer time excluding epi/CT cell invasion
Cons: RR of 1.43 (95% CI: 0.85-2.39) (NSSD) between the cross linked vs non-cross linked, with a marginal tendency towards higher exposure in the cross-link membrane group (Garcia et al. 2017 systematic review)
The glutaraldahyde makes it too rigid! (Dr. Wang)
What are Polymer-based Membranes made of? (In general and specifically)
Chemically synthesized aliphatic polyesters.
Polylactide (PLA), Polyglycolide (PGA), Trimethylcarbonate
What is the benefit of polymer based membranes?
Better mechanical stability vs collagen
How are polymer based membranes reorbed? What does it result in?
Hydrolytic activity (Krebs cycle) - Acidic biproducts released - may cause fibrous layer??
What is the degredation rate of Polymer membranes dependent on?
pH, presence of mechanical strains, enzymes, bacterial infection, COMPOSITION
Which material resorbs slower for polymer membranes? (citation) how can it be modified?
PLA is more stable than PGA (Resorbs slower) (Tatakis et al. 1999)
Adding crosslinked D-Lactide or Glycolide allows faster degradation
What membrane is PLA alone? How long do these take to resorb?
PLA alone does not appear to be available???
Poly-D,L-Lactide: 6-12mo
Poly-D,L-Lactide, Co-Glycolide: 5-6mo
Jiaolong Wang et al. 2016
What is a CON of PLA or PLGA membranes?
Although PLA- and PLGA-based membranes are non-cytotoxic and biodegradable, the releases of oligomers and acid byproducts during degradation may trigger inflammation reactions and foreign body response in vivo (Zwahlen et al. 2009, COIR, RCT)
What is ADM composed of?
Human, porcine, or bovine skin
What can ADM be used for? citation
As an alternative to autogenous KG - Build KG around implants/teeth or for root coverage (de Andrade 2007)
What does lit say about ADM and infection?
May not be colonized sitnificantly by periodontopathic bacteria - even when exposed completely, still incorporated into host and heals (de Andrade 2007)
What is Amnion Chorion derived from?
Human placenta - inner and outer membrane (amnionic membrane - chornionic membrane)
CLINICAL benefits of Amnion-Chorion membranes? Citation
Lack stiffness - easily adapted to infrabony defects - no trimming/suturing needed - less surgical time/flap reflection
(Szurman et al. 2006)
Healing benefits of Amion-Chorion membranes (citation)
Contain growth factors (PDGF-AA/VEGF (vascular endothelial…))
Could enhance wound healing and reduce bacterial contamination decreasing risk of exposure
(Gulameasbasse et al 2020)
Compare and contrast resorbabl vs. non-resorbable membranes
NRM: Non-resorbable membrane
RM: Resorbable membrane
Space making: NRM better
Bac resistance: NRM better
Cell attachment/prolif: RM better
Biologic properties:
NRM: biocompatible/Bio-inert/requires removal
RM: biocompatible/bio-INTERACTIVE/biodegradable
Post op exposure: NRM MORE
What are the disadvantages of non-resorbable membranes?
2nd surgery
High membrane exposure
More gingival recession
Can resorbable or non-resorbable tolerate exposure better?
NON-RESORBABLE (tolerate better - but more often)
What rand of particle size should bone grafts be? (citation)
250-750microns
Kathagen et al. 1984
What negative effects can particle size cause? what size causes these issues?
<125microns: Foreign body reaction
>1000microns: sequestration
Kathagen 1984
How do bone grafts help in GTR? Citaion
Maximize regenerative potential via osteoinduction, osteoconduction, and clot stabilization (Cortellini & Tonetti 2015)
Where can Autograft be harvested from?
tuberosity ramus exostoses alveolar ridge mental symphysis post-extraction sites edentulous ridge
Optimal time to take auto from extraction socket
8-12weeks (Evian et al 1982
What is different from tuberosity vs ramus/chin graft?
Tuberosity is highly cancellous
Chin/Ramus are monocortical
Buck et al. 1989/1990
Screening and freezing Allograft reduces risk of HIV transmission to 1/8million
What properties do allografts have? (ciotation)
Mostly osteoconductive, except DFDBA which may have osteoinductive abilities (Wang & Cooke 2005)
What is the difference between DFDBA/FDBA
FDBA looses cell viability and acts as a scaffold
DFDBA has exposed BMPs that can induce cell recruitment
How does DFDBA perform in GTR procedures?
Series of studies with DFDBA vs no graft in GTR
DFDBA had new attachment apparatus, bone, and cementum (TRUE NEW ATTACHMENT)
Bowers et al. 1989
What properties does Xenograft have?
ONLY OSTEOCONDUCTIVE serves as a scaffold
Which is better for GTR, Xenograft or Allograft? ()citation)
NSSD - Richardson et al. 1999
What are examples of Alloplast?
Hydroxyapatite, beta tricalcium phosphate, bioactive glass, some polymers
What are the 3 processes for sterilizing allograft?
Freezing/Ethonol bath (FDBA)
Freezing/Ethanol bath/HCl (DFDBA)
Solvent-dehydrated (Human HA)
What characteristic dos Puros have?
Osteoconductive (Human HA)
What are the most common biologics used today?
PRP ( Platelet rich plasma)
rhPDGF (recombinant human platelet derived growth factor)
EMD
What is PRF/PRP composed of?
PDGF, I-LGF, VEGF, TGF-b
What is the MOA of PRP/PRF?
Provides GFs and Platelets
Indications for PRF/PRP
Recession coverage/barrier membrane/Sticky Bone
What is the MOA of rhPDGF?
Causes Chemotaxis and Cell Proliferation
What are the indications for rhPDGF?
Intrabony defects
Furcations
Recession
in combo with allograft/xenograft
What does rhPDGF have FDA approval for?
Intrabony defects
Furcations
Gingival recessions
What is EMD composed of
90% Amelogenin
10% includes tuftelin, ameloblastin, enamelin and enamel proteases.
What is the MOA of EMD?
it induces cementogenesis
What are the indications for EMD?
Intrabony defects
Class II Furcations
Recession coverage
What is EMD FDA approved for?
Intrabony defects
Optimizing tissue height in esthetic zone
What is the MOA of BMP?
Increased proliferation/mineralization
Expression of alkaline phosphate and osteocalcin
Indicaitons for BMP
systemic/anatomic conditions where successful bone regen cant be achieved with conventional grafts
NOT WITH DBBM
What is BMP FDA approved for?
Sinus augmentation
Socket preservation
What study is important when discussing regeneration using bone graft?
Series of histological studies by Bowers in 1989
Describe histological studies on regen using bone graft
Bowers 1989 (series) Used DFDBA vs no graft in a submerged and non-submerged environment
DFDBA had more new PDL, bone and cementum
Regeneration only in the submerged group
