With the possible exception
of implant fixtures (and their prosthetic attachments), no area in
periodontics has proliferated so rapidly as periodontal regeneration
materials. Today commercial preparations are marketed almost as soon
as the first piece of research is published. Some pan out and some
are gone as fast as last week's average movie. Now, with the advent
of ridge augmentation to receive implants and sinus lifts, grafting
materials are being designed for specific applications. Some are
engineered to maximize the space for bone ingrowth while others provide a
scaffold and readily available inorganic components of bone that migrating
reparative cells can utilize. Biologic modifiers are being
introduced to increase the likelihood of regeneration. In addition,
some manufacturers have begun to individually test donor materials, such
as allografts from tissue banks, to determine the graft's ability to
induce bone formation in lab animals in areas which would not normally
form bone. This increases the likelihood that the graft will
actually induce surrounding tissues to form new bone. Inconsistent
induction potential in commercially available allogenic grafting materials
may be partly responsible for the variability in study results on osseous
grafts. Continuing refinements such as these will ultimately improve
the predictability of results.
The search for the "perfect"
grafting material has focused on bone and bone substitutes, and more
recently had added biologic modifiers; that is, substances which influence
the activity of the cells responsible for new periodontal ligament
formation. Autogenous bone grafts are the "gold standard" for
comparing the success of other graft materials. The table below
shows the three categories of non-autogenous materials now being used in
periodontics, with major examples of each within the category. It is
obvious that the choice of material, or combination or materials, is
becoming increasingly complex. We want to inform you of these
materials so you may share the wide variety of possibilities with your
patients.
For periodontal defects bone
substitutes are either specialized forms of DFDBA (decalcified freeze
dried bone allograft), other animal forms (xenografts) or synthetic
substitutes. The specialized forms of DFDBA presently marketed for
periodontal defects are Grafton gel and Regeneration Technologies
Regenafil paste. Both materials have excellent retention within the
surgically debrided defect, more than conventional materials.
Grafton uses glycerol, a water soluble base, as a vehicle to carry DFDBA
and is about 50% DFDBA after placement.
Bone
Substitutes
| For Periodontal
Defects-Bone Substitutes |
For Periodontal
Defects-Biologic Modifiers |
For Ridge Augmentation-
Bone Substitutes |
| Regenafil (RTI), Grafton
gel |
Emdogain (enamel matrix
derivative) |
DFDBA, FDBA (bone allografts) |
| Bio-Oss, Osteograf-N
(bovine bone skeleton) |
Pep-Gen (cell binding peptide |
Regenaform, Regenafil, Grafton
Putty, Flex |
| Perioglass, Biogran (synthetic
mineral sources) |
PDGF (Platelet derived growth
factor) |
Bio-Oss Cortical Block |
Grafton uses a random lot testing to insure that the DFDBA incorporated
is osteoinductive. Regenafil (RTI) is 80% bone by volume after
implantation as its vehicle is a gelatin which results in less water
absorption during the grafting process. Regenafil comes
refrigerated, needs to be warmed prior to placement and solidifies as it
cools. The liquid-solid temperature range is very narrow.
Above 102-103 degrees it is a liquid/gel and at body temperature it is a
solid. RTI tests each batch of materials for its osteoblastic
induction potential. On an induction scale of 1-4, all RTI materials
must be at least a 2.
The currently available animal derived periodontal
defect grafting materials are Bio-Oss, Osteograf-N, Interpore 200 and
Biocoral. Biocoral is calcium carbonate derived from natural coral,
is resorbable and biocompatible. Bio-Oss is bovine bone from which all the
organic material has been extracted, yielding a microporous structure very
similar to autogenous bone in its chemical composition and
microstructure. Osteograf-N is also a bovine bone, but with a
crystalline structure rather than a microporous structure. Synthetic
bone substitutes include bioactive glasses (Perioglass and Biogran) and a
porous methylmethacrylate (HTR). HTR has been shown to increase bone
apposition only when in close contact to adjoining bone, such as along an
extraction socket wall. The bioactive glasses are particulate
materials, slowly resorb and when mixed with fluids in a periodontal
defect form an adherent surface layer of silicon, calcium, flouride and
sodium which binds the graft to bone. They obliterate defects well,
are not inductive of bone formation, but conduct mineralization by
promoting absorption and concentration of proteins used by osteoblasts to
form the extracellular matrix of bone.
The key characteristics being sought in these
materials are the ability to adhere to the defect, encourage clot
formation and rapid vascularization, and provide a physical scaffold along
with the minerals needed for bone formation. In the case of DFDBA
and autogenous bone, components of the graft act to induce osteoblastic
transformation and proliferation. It is the nature of these inducing
agents within bone grafts that have led researchers to search for the
biologic modifiers in grafts that encourage defect repair. The three
most common biologic modifiers today are Emdogain, Pep-Gen and PDGF.
Emdogain is an enamel matrix, protein-rich gel
extracted from pig tooth buds. Enamel matrix protein is secreted by
Hertwig's epithelial root sheath and is responsible for initiating the
original formation of acellular cementum on the developing tooth
root. In periodontal defects the rationale for its use suggests that
host PDL cells/fibroblasts will be transformed into cementoblasts and
begin forming new attachments of connective tissue to the root
surface. These enamel matrix proteins when suspended in a
thickening agent (propylene glycol alginate - PGA) are retained on root
surfaces for up to two weeks. The enamel matrix derivative has also
been demonstrated by Gestrelius et al to retard downgrowth of
epithelium. In the ten clinical studies of this material published
since 1997, including two human histological cases reported, attachment
level gains have been compatible to guided tissue regeneration
membranes. By comparison of similar studies Emdogain appears to
produce results similar to DFDBA. Autogenous bone remains the "gold
standard" for regeneration studies.
Pep-Gen is a synthetic amino acid sequence identical
to that found in the non-allogenic portion of the collagen molecule.
The material is combined with an anorganic microporous bovine bone.
The portion of collagen protein incorporated in the graft is thought to be
responsible for binding fibroblasts and osteoblasts in the material
matrix. Yukna, in a histologic study of four human specimens, showed
two of the four specimens had new periodontal attachment over previously
diseased root surfaces. In the only clinical study to date, Yukna et
al found greater defect fill in Pep-Gen treated defects but no greater
gain in attachment levels compared to DFDBA.
The most recent biologic modifier is platelet
derived growth factor (PDGF). Since this material is derived from
the patient's own platelet rich plasma it is not a commercial
preparation. Marx et al have described this process. One
hundred and fifty milliliters of whole blood is drawn into a citrated
container. The platelet rich plasma is separated using a platelet
separator, like a centrifuge, and it is added to autogenous or allogenic
bovine bone. After placement of the graft material-enriched PDGF, a
coat of PRP plasma is placed over the graft area and the flaps closed.
In Marx's study of mandibular defects, both the
amount and rate of bone formation were increased. This could be
particularly significant for patients whose bone formation is reduced such
as the elderly, those with diabetes or osteoporosis. Platelet rich
plasma is high in concentration of three growth factors: PDGF (platelet
derived growth factor), TGF-B (transforming growth factor beta) and IGF
(insulin-like growth factor). The spin down process of platelets
increases the concentration by 300%. PRP/PDGF is just beginning to
receive clinical utilization.
When you suggest the possibility of osseous
reconstruction to your patients, be it for periodontal defects or
pre-implant osseous reconstruction, rest assured that we will make our
best effort to choose the grafting approach most suited to your patients
total needs. If you have questions about the use of any of these
materials please contact our office.
