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References Animal Studies

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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