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Research
The Laboratory for Applied Periodontal & Craniofacial
Regeneration has developed discriminating preclinical
models to evaluate the biology of periodontal wound
healing/regeneration under optimized conditions and
to evaluate the efficacy and safety of candidate biomaterials,
devices, and biologic factors intended for periodontal
regeneration. In collaboration with corporate partners
we have evaluated occlusive and novel macro-porous devices
(developed in our laboratories) for guided tissue regeneration
(GTR), various bone biomaterials, and matrix, growth
and differentiation factors including fibronectin, PGE1,
rhTGF-1, rhBMP-2, rhBMP-12, and rhGDF-5 in advanced
periodontal defects.
Similarly, we have developed clinically relevant discriminating
preclinical models to evaluate alveolar augmentation
and oral implant osseointegration under optimized conditions,
and in particular evaluate the biologic potential of
bone morphogenetic proteins (BMPs) including rhBMP-2,
rhOP-1/rhBMP-7, rhGDF-5, and other candidate biologics
including osteoactivin and platelet-rich-plasma (PRP),
as well as bone biomaterials and novel devices for guided
bone regeneration (GBR).
Our studies on periodontal wound healing/regeneration
suggest that wound stability during the early healing
phase will allow maturation of the tooth gingival flap
interface into a new connective tissue attachment rather
than the formation of an epithelial attachment (long
junctional epithelium). Root conditioning and/or surgical
implantation of biologic agents, bone biomaterials,
and devices for GTR may dramatically alter the outcomes
of wound healing for better or worse.
Our studies on alveolar augmentation and oral implant
osseointegration have explained merits and shortcomings
of current clinical treatment protocol including bone
biomaterials and guided bone regeneration (GBR). Our
studies further suggest that BMPs have an unparalleled
potential to augment alveolar bone and support implant
osseointegration and long-term functional loading. Inclusion
of BMPs for alveolar augmentation and osseointegration
will not only enhance predictability of existing clinical
protocol but also radically change current treatment
paradigms.
Keynote Studies
Critical-size, 5-mm, supraalveolar, periodontal defect
implanted with an occlusive, space-providing ePTFE membrane.
The large green arrow points to newly regenerated bone
reaching from the apical aspect of the defect to the
cemento-enamel junction, the ePTFE membrane provides
a suitable space for periodontal regeneration, the small
green arrows delineate the apical aspect of the supraalveolar
periodontal defect. The second photomicrograph shows
the membrane collapsed or compressed onto the root with
minimal regeneration as a consequence. The third photomicrograph
shows a sham-surgery control also with minimal regeneration,
the mucogingival flap being collapsed or compressed
onto the root. Finally, the fourth photomicrograph with
a large yellow arrow shows a site where the membrane
has been exposed to oral cavity resulting in infection
and necrosis without any regeneration of periodontal
tissues. This study points to the critical importance
of unobstructed space-provision for periodontal regeneration.
Healing interval 8 weeks. For detail see Sigurdsson
TJ, Hardwick R, Bogle GC, Wikesjo UME. Periodontal repair
in dogs: Space provision by reinforced ePTFE membranes
enhances bone and cementum regeneration in large supraalveolar
defects. Journal of Periodontology 1994; 65:350-356.
Critical-size, 5-mm, supraalveolar, periodontal defect
implanted with an occlusive, space-providing ePTFE membrane.
The high magnification photomicrographs from the apical,
mid, and coronal aspect of the defect show regeneration
of the periodontal attachment including cellular cementum,
a functionally oriented periodontal ligament, and alveolar
bone. Healing interval 8 weeks. For detail see Sigurdsson
TJ, Hardwick R, Bogle GC, Wikesjo UME. Periodontal repair
in dogs: Space provision by reinforced ePTFE membranes
enhances bone and cementum regeneration in large supraalveolar
defects. Journal of Periodontology 1994; 65:350-356.
Critical-size, 5-mm, supraalveolar, periodontal defect
implanted with an occlusive ePTFE membrane and an osteoconductive
biomaterial. Note significant regeneration of alveolar
bone in the left photomicrograph in absence of the biomaterial.
It is shown that the more biomaterial is used the less
tissue regeneration occurs raising the question of any
benefit of using slowly resorbing or non-resorbable
bone biomaterials in conjunction with periodontal regenerative
surgery. This study points to the critical importance
of unobstructed space-provision for periodontal regeneration.
Healing interval 4 weeks. For detail see Trombelli L,
Lee MB, Promsudthi A, Guglielmoni PG, Wikesjo UME. Periodontal
repair in dogs: Histologic observations of guided tissue
regeneration with a prostaglandin E1 analog/methacrylate
composite. Journal of Clinical Periodontology 1999;
26:381-387.
Critical-size, 5-mm, supraalveolar, periodontal defect
implanted with occlusive and macro-porous, space-providing
ePTFE membranes, the photomicrographs show a site implanted
with the porous membrane. Note significant periodontal
regeneration including a functionally oriented periodontal
ligament, cellular cementum, and alveolar one approaching
the cemento-enamel junction (large green arrow). Similar
results were found in sites implanted with the occlusive
membrane clearly suggesting that tissue occlusion is
not critical requirement for periodontal regeneration.
Healing interval 8 weeks. For detail see Wikesjo UME,
Lim WH, Thomson RC, Hardwick WR. Periodontal repair
in dogs: Gingival tissue occlusion, a critical requirement
for guided tissue regeneration? Journal of Clinical
Periodontology 2003; 30:655-664.
Critical-size, 5-mm, supraalveolar, peri-implant defect
receiving GBR (occlusive space-providing ePTFE membrane)
with or without a decalcified freeze-dried bone biomaterial
(DFDBA); note limited regeneration of alveolar bone
in absence and presence of the DFDBA biomaterial indicating
that 1) the innate regenerative potential of alveolar
bone is limited (GBR), and 2) the DFDBA biomaterial
has limited, if any, osteoinductive and/or osteoconductive
properties to support bone regeneration. Also compare
the results shown to that observed following GTR suggesting
that GTR and GBR represents separate biologic events.
The green lines delineate the level of the surgically
reduced alveolar crest. Healing interval 16 weeks. For
detail see Caplanis N, Sigurdsson TJ, Rohrer MD, Wikesjo
UME. Effect of allogeneic, freeze-dried, demineralized
bone matrix on guided bone regeneration in supra-alveolar
peri-implant defects in dogs. The International Journal
of Oral & Maxillofacial Implants 1997; 12:634-642.
Critical-size, 5-mm, supraalveolar, peri-implant defect
receiving rhBMP-2/ACS, GBR, or rhBMP-2/ACS combined
with GBR using a macro-porous, space-providing ePTFE
membrane. Note how the rhBMP-2 induced bone fills the
space provided by the membrane (green arrowheads) whereas
rhBMP-2/ACS alone provides very irregular bone formation
(left). GBR alone (right center) provides limited, if
any, regeneration of alveolar bone. The green arrows
delineate the level of the surgically reduced alveolar
crest. Healing interval 8 weeks. For detail see Wikesjo
UME, Qahash M, Thomson RC, Cook AD, Rohrer MD, Wozney
JM, Hardwick WR. Space-providing expanded polytetrafluoroethylene
devices define alveolar augmentation at dental implants
induced by recombinant human bone morphogenetic protein-2.
Clinical Implant Dentistry and Related Research 2003;
5:112-123 and Wikesjo UME, Qahash M, Thomson RC, Cook
AD, Rohrer MD, Wozney JM, Hardwick WR. rhBMP-2 significantly
enhances guided bone regeneration. Clinical Oral Implants
Research 2004; 15:194-204.
Critical-size, 5-mm, supraalveolar, peri-implant defect
receiving rhBMP-2/alpha-BSM, the photomicrographs show
the three implants receiving rhBMP-2, the far right
implant received alpha-BSM alone (control). The green
arrows delineate the level of the surgically reduced
alveolar crest. Note robust bone formation reaching
the implant platform at sites receiving rhBMP-2/alpha-BSM.
The induced bone exhibits qualities of the adjoining
resident bone including relevant implant osseointegration.
Healing interval 16 weeks. For detail see Wikesjo UME,
Sorensen RG, Kinoshita A, Wozney JM. rhBMP-2/alpha-BSM
induces significant vertical alveolar ridge augmentation
and dental implant osseointegration. Clinical Implant
Dentistry and Related Research 2002; 4:173-181.
Re-osseointegration following implantation of rhBMP-2/ACS
at implant exposed to plaque and calculus for 11 months.
The clinical view shows the cleaned implant prior to
implantation of rhBMP-2/ACS, the green arrow points
to the aspect of the implant shown in the photomicrographs.
The black arrows delineate the apical aspect of the
peri-implantitis defect, the green bracket depicts a
high magnification area showing re-osseointegration.
Note that the rhBMP-2 induced bone exhibits qualities
of the contiguous resident bone. Healing interval 16
weeks. For detail see Hanisch O, Tatakis DN, Boskovic
MM, Rohrer MD, Wikesjo UME. Bone formation and reosseointegration
in peri-implantitis defects following surgical implantation
of rhBMP-2. The International Journal of Oral &
Maxillofacial Implants 1997; 12:604-610.
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