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Bone
induction by porous glass ceramic made from Bioglass (45S5)
Yuan H, de Bruijn JD, Zhang X, van Blitterswijk CA, de Groot K.
Biomaterials Research
Group, Leiden University, The Netherlands. huipin.yuan@isotis.com
Porous
glass ceramic, which was prepared from Bioglass powder (45S5, U.S. Biomaterials)
by foaming with diluted H(2)O(2) solution and sintering at 1000 degrees C for 2
h, was implanted as cylinders (5 mm in diameter and 6 mm in length) in thigh
muscles of dogs for 3 months. Histological observation was made on thin
un-decalcified sections. Bone formation was histologically found in pores of all
implants (X16) retrieved from 16 dogs. The bone tissue was also identified with
backscattered scanning electron microscopy observation (BSE) and energy
dispersive X-ray microanalysis (EDX). This is the first report of bone induction
in soft tissues of animals by glass ceramic that has long been recognized as a
bioactive (osteoconductive) biomaterial. The present results justify the impetus
to investigate the osteoinductivity of calcium phosphate-based biomaterials, to
study the mechanism of bone induction (osteoinduction) by calcium
phosphate-based biomaterials, to develop osteoinductive calcium phosphate-based
biomaterials, and to examine the relation between osteoinduction and
osteoconduction. Copyright 2001 John Wiley & Sons, Inc.
J Biomed Mater Res 2001 May 1;58(3):270-6

Assessment of resorbable bioactive material for grafting of
critical-size cancellous defects.
Wheeler DL, Eschbach EJ, Hoellrich RG, Montfort MJ, Chamberland DL. Department of Orthopaedics, University of Florida, Gainesville
32610, USA.
Bioactive glasses form a surface apatite layer in vivo that enhances
the formation and attachment of bone. Sol-gel Bioglass graft
material provides greater nanoscale porosity than bioactive glass
(on the order of 50-200 A), greater particle surface area, and
improved resorbability, while maintaining bioactivity. This study
histologically and biomechanically evaluated, in a rabbit model,
bone formed within critical-sized distal femoral cancellous bone
defects filled with 45S5 Bioglass particulates, 77S sol-gel
Bioglass, or 58S sol-gel Bioglass and compared the bone in these
defects with normal, intact, untreated cancellous bone and with
unfilled defects at 4, 8, and 12 weeks. All grafted defects had more
bone within the area than did unfilled controls (p < 0.05). The
percentage of bone within the defect was significantly greater for
the 45S5 material than for the 58S or 77S material at 4 and 8 weeks
(p < 0.05), yet by 12 weeks equivalent amounts of bone were observed
for all materials. By 12 weeks, all grafted defects were equivalent
to the normal untreated bone. The resorption of 77S and 58S
particles was significantly greater than that of 45S5 particles (p <
0.05). Mechanically, the grafted defects had compressive stiffness
equivalent to that of normal bone at 4 and 8 weeks. At 12 weeks,
45S5-grafted defects had significantly greater stiffness (p < 0.05).
At 8 and 12 weeks, all grafted defects had significantly greater
stiffness than unfilled control defects (p < 0.05). In general, the
45S5-filled defects exhibited greater early bone ingrowth than did
those filled with 58S or 77S. However, by 12 weeks, the bone
ingrowth in each defect was equivalent to each other and to normal
bone. The 58S and 77S materials resorbed faster than the 45S5
materials. Mechanically, the compressive characteristics of all
grafted defects were equivalent or greater than those of normal bone
at all time points.
J Orthop Res 2000 Jan;18(1):140-8

Bone
In-Fill of Non-Healing Calvarial Defects Using Particulate Bioglass®
and Autogenous Bone
Bergman SA, Litkowski LJ Department of Oral and Mzxillofacial Surgery, Department of
Restorative Dentistry Dental School, University of Maryland at
Baltimore, 666 West Baltimore Street, Baltimore, MD
The purpose of this study was to evaluate the bone in-fill
surgically created non-healing calvarial defects in the rabbit
model, when using particulate Bioglass® 90-710 µm, 110-310 µm, and
spherical, alone and in combination with autogenous calvarial
cortical bone dust. Results indicate that the combination of
particulate Bioglass, 9-710 µm and 50% autogenous calvarial cortical
bone dust was the most efficacious combination in inducing bone
in-fill of non-healing calvarial defects in the rabbit model. This
was followed by particulate Bioglass 90-710 µm alone. The
particulate Bioglass 110-310 µm showed little if any bone in-fill at
all time intervals after placements as did the spherical Bioglass
particles.

Quantitative comparison of bone growth behavior in granules of
Bioglass, A-W glass-ceramic, and hydroxyapatite.
Oonishi H, Hench LL, Wilson J, Sugihara F, Tsuji E, Matsuura M, Kin
S, Yamamoto T, Mizokawa S. Department of Orthopedic Surgery, Artificial Joint Section and
Biomaterial Laboratory, Osaka-Minami National Hospital. 2-1,
Kidohigashi-machi, Kawachinagano-City, Osaka, 586-8521, Japan.
The hypothesis that bioactive glass particulate increases the rate
of bone proliferation over that of synthetic hydroxyapatite and
bioactive glass-ceramic was tested in these experiments. Three types
of bioactive particles-45S5 Bioglass(R), synthetic hydroxyapatite,
and A-W glass-ceramic-were implanted in 6-mm-diameter holes drilled
in the femoral condyles of mature rabbits. Bone growth rate was
measured using an image processor. 45S5 Bioglass(R) produced bone
more rapidly than either A-W glass-ceramic or hydroxyapatite. At the
later time periods, 45S5 Bioglass(R) was resorbed more quickly than
A-W glass-ceramic. Synthetic hydroxyapatite was not resorbed at all.
Backscattered electron imaging suggested that the resorption process
occurred by solution-mediated dissolution, which produced chemical
changes in the enclosed particulate. It was concluded that the rate
of bone growth correlates with the rate of dissolution of silica as
the particles resorb. Copyright 2000 John Wiley & Sons, Inc.
J Biomed Mater Res 2000 Jul;51(1):37-46

Comparative bone growth behavior in granules of bioceramic materials
of various sizes.
Oonishi H, Hench LL, Wilson J, Sugihara F, Tsuji E, Kushitani S,
Iwaki H. Department of Orthopaedic Surgery, Artificial Joint Section and
Biomaterial Research Laboratory, Osaka-Minami National Hospital,
677-2, Kido-Cho, Kawachinagano-Shi, Osaka 586, Japan.
Various bioceramic materials were implanted into 6-mm-diameter holes
made in the femoral condyles of mature Japanese white rabbits using
different-sized granules to find an optimal material and granule
diameter for use as a bone graft. Bioceramics include a bioinert
ceramic (Alumina), surface-bioactive ceramics [hydroxyapatite (HAp)
and Bioglass(R)], and resorbable bioactive ceramics [alphatricalcium
phosphate (alpha-TCP), beta-TCP, tetracalcium phosphate (TeCP), Te.
DCPD, Te. DCPA, and low-crystalline HAp]. Granule sizes were
100-300, 10, and 1-3 microm. Bone growth behavior varied with the
kind of bioceramic and the size used. For surface-bioactive
ceramics, 45S5 Bioglass(R) led to more rapid bone proliferation than
synthetic HAp. In resorbable bioactive ceramics, the order of
resorption was: low-crystalline HAp and OCP > TeCP, Te DCPD, Te DCPA
> alpha-TCP, beta-TCP. In terms of biocompatibility, alpha-TCP was
better than beta-TCP. Copyright 1999 John Wiley & Sons, Inc.
J Biomed Mater Res 1999 Jan;44(1):31-43

Effect of bioactive glass particle size on osseous regeneration
of cancellous defects.
Wheeler DL, Stokes KE, Hoellrich RG, Chamberland DL, McLoughlin
SW. Orthopaedic Research Laboratory, Oregon Health Sciences
University, Portland 97201, USA.
The bioactive glass known as Bioglass or Perioglass (USB) (US
Biomaterials, Alachua, FL) has proven to be an effective graft
material owing to the apatite layer which forms on the surface
of the glass, promoting bone formation. USB particles range in
size from 90 to 710 microns in diameter, as determined by
optical microscopy. A similar bioactive material, BioGran (OV) (Orthovita,
Malvern, PA), was developed to limit the particle size of 4555
to the range between 300 and 360 microns, as determined by
sieving. The objective of this study was to histologically and
biomechanically compare the 4555 bioactive glass, produced by US
Biomaterials, in a wide particle range (USB) to the narrower
particle range glass produced by Orthovita (OV) The grafted
defects will then be compared to normal cancellous bone (NORM)
of the distal femur in rabbits. Histologically, more bone was
quantified at both 4 and 12 weeks within the defects filled with
USB and NORM when compared to the limbs filled with OV (p <
0.05). The OV particles had greater particle axes and larger
particle areas on average than the USB particles (p < 0.05).
However, the particle axis and area of the two materials
decreased with time at a similar rate. Biomechanically, the USB-
and OV-grafted defects had comparable peak compressive load,
compressive stiffness, and compressive modulus which were
equivalent to normal bone.
J Biomed Mater Res 1998 Sep 15;41(4):527-33 Comment in: J
Biomed Mater Res. 1999 Aug; 46(2):301-4

Particulate bioglass compared with hydroxyapatite as a bone graft
substitute.
Oonishi H, Kushitani S, Yasukawa E, Iwaki H, Hench LL, Wilson J,
Tsuji E, Sugihara T. Department of Orthopaedic Surgery, Artificial Joint Section and
Biomaterial Research Laboratory, Osaka-Minami National Hospital,
Kido-Cho, Kawachinagano-Shi, Osaka, Japan.
Bioactive ceramics, notably hydroxyapatite, have been used
clinically in various situations in which bone augmentation and
restoration are required. Particulate material has been used either
alone or in conjunction with freeze dried or autologous bone, with
variable clinical success. In this study a bioactive glass, 45S5
Bioglass, has been compared with hydroxyapatite in an animal model
to discover whether the 2 major disadvantages of hydroxyapatite may
be overcome. These are the difficulty of placing and retaining the
particulate in the defect and the length of time needed before full
bony restoration is achieved. Bioglass is shown to be easy to
manipulate and hemostatic and allows full restoration of bone in 2
weeks, rather than the 12 weeks needed for the particulate
hydroxyapatite to produce a comparable response. The Bioglass
particulate is used up in the process, and any problems that may be
associated with the production of a composite of bone and
biomaterial are avoided in the fully restored bone. In any procedure
that requires bony augmentation, this rapid response to Bioglass is
expected to provide a clinical advantage
Clin Orthop 1997 Jan;(334):316-25

Quantitative rates of in vivo bone generation for Bioglass® and
hydrosyapatite particles as bone graft substitute
Fujishiro Y, Hench LL, Oonishi H Department of Materials, Imperial College of Science, Technology and
Medicine, Prince Consort Road, London SW7 2BP, UK Department of Orthopaedic Surgery, Artificial Joint Section and
Biomaterials Research Laboratory, Osaka-Minami National Hospital,
Kido-Cho, Kawachinagano-Shi, Osaka 586, Japan
Rates of in vivo bone generation were characterized by
point-counting analysis of particulate Bioglass® and synthetic
hydroxyapatite (HA) in rabbit femora. New bony tissue was observed
in ~20% of the image area around Bioglass particles at 1 week, and
the degree of trabecular bone growth increased with time. The
interparticle space of Bioglass was filled by 80% bonding bone
between6 and 12 weeks. The rate constants of trabecular bone growth
in the presence of Bioglass were ~10.9 x 10 -3d-1 at the periphery
of the implantation site. HA particles led to smaller rate
constants of ~4.6 x 10-3d-1 at the periphery, and the HA particles
developed very small amounts of bridging bone. The quantitative
rate of bone growth matched well with previously measured bioactive
indices of the materials.
J of Materials Science: Materials in Medicine 8 (1997) 649-652

Regeneration of peri-implant infrabony defects using PerioGlas:
a pilot study in rabbits.
Johnson MW, Sullivan SM, Rohrer M, Collier M. Department of Oral and Maxillofacial Surgery, University of
Oklahoma, Oklahoma City, USA.
PerioGlas is a silicate-based synthetic bone augmentation
material that has been used to fill periodontal defects with
bonding and integration to both soft tissue and bone. The
purpose of this research was to determine the PerioGlas
interface with titanium dental implants and bone. Seven live
rabbits were used; however, one rabbit was euthanized at 3 days
as a result of a tibial fracture through the implant placement
site. Each rabbit received four 3.3 x 8 mm Imtec titanium
plasma-sprayed dental implants, two in each proximal tibia. One
implant in each rabbit was placed in the standard fashion. Two
implants in each rabbit had a surgically created defect adjacent
to one side of the coronal aspect of the implant. The defect was
subsequently filled with PerioGlas. One implant in each rabbit
had a surgically created defect that was not filled with
PerioGlas. The rabbits were sacrificed at 1, 2, 3, 6, 12, and 24
weeks. Each specimen was prepared for histologic viewing,
yielding a nondecalcified specimen demonstrating the interface
of bone, implant, and PerioGlas. The results demonstrate
peripheral formation of osteoid, followed by bone deposition
within the defect from host (surgical margin) bone, toward the
implant. The new osteoid and bone form around the PerioGlas
particles. Newly formed trabeculae connect these areas of
osteoid and new bone around the PerioGlas, interconnecting the
PerioGlas particles. The new bone eventually reaches the
implant, and osseointegration occurs with incorporation of the
PerioGlas particles.
J Biomed Mater Res. 1999 Aug;46(2):301-4.

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