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Bone graft extenders
Geisler, F. H. (2005), J Neurosurg Spine 3(4): 332; author reply 332-3.

Bone graft extenders, substitutes, and osteogenic proteins
Barrack, R. L. (2005), J Arthroplasty 20(4 Suppl 2): 94-7.
Abstract: A number of products that serve as a bone graft substitutes or graft extenders are currently available. Osteoconductive products provide a porous 3-dimensional structure that encourages bone ingrowth. These materials are readily resorbed by osteoclasts leading to turnover into host bone at variable rates. Some calcium phosphate products act as cements in that they are liquid upon preparation and harden at body temperature. These cements resist compressive forces but are not effective in resisting shear or torsion. Calcium sulfate resorbs more quickly than calcium phosphate and has the potential to serve as a carrier for drugs or growth factors. Preclinical studies have shown that the osteoinductive capacity of autograft and allograft bone can be improved substantially with the addition of osteogenic proteins. Although no detailed clinical studies have been reported to date, anecdotal reports of their use with and without bone graft indicate results consistent with those obtained in preclinical studies.

Bone induction in craniofacial defects
Nacamuli, R. P. and M. T. Longaker (2005), Orthod Craniofac Res 8(4): 259-66.
Abstract: Reconstruction of craniofacial bony deficiencies, whether acquired through trauma or as a result of treatment for disease, is a chronic problem. Although numerous approaches utilizing a wide array of materials ranging from alloplastic materials to autogenous bone grafts have been employed to achieve bony replacement, no ideal clinical approach exists. In this brief review, we will provide an overview of current approaches to treating craniofacial bony defects. We will then discuss advances being made in the design of scaffolding materials and potential candidate cell types with which to design tissue-engineered constructs for craniofacial skeletal repair.

Bone inductive biomaterials in facial plastic and reconstructive surgery
Toriumi, D. M. and K. Robertson (1993), Facial Plast Surg 9(1): 29-36.

Bone in-growth induced by biphasic calcium phosphate ceramic in femoral defect of dogs
Manjubala, I., T. P. Sastry, et al. (2005), J Biomater Appl 19(4): 341-60.
Abstract: Biphasic calcium phosphate (BCP) ceramics consisting of hydroxyapatite (HA) and tricalcium phosphate (TCP) has been used as a bone graft material during the last decade. In this paper, we report the bone in-growth induced by BCP ceramic in the experimentally created circular defects in the femur of dogs. This BCP ceramic consists of 55% hydroxyapatite (HA) and 45% b-tricalcium phosphate (TCP) prepared in situ by the microwave method. The defects were created as 4-mm holes on the lateral aspect of the femur of dogs and the holes were packed with the implant material. The defective sites were radiographed at a period of 4, 8, and 12 weeks postoperatively. The radiographical results showed that the process of ossification started after 4 weeks and the defect was completely filled with new woven bone after 12 weeks. Histological examination of the tissue showed the formation of osteoblast inducing the osteogenesis in the defect. The collageneous fibrous matrix and the complete Haversian system were observed after 12 weeks. The blood serum was collected postoperatively and biochemical assays for alkaline phosphatase activity were carried out. The measurement of alkaline phosphatase activity levels also correlated with the formation of osteoblast-like cells. This microwave-prepared BCP ceramic has proved to be a good biocompatible implant as well as osteoconductive and osteoinductive materials to fill bone defects.

Bone ingrowth simulation for a concept glenoid component design
Andreykiv, A., P. J. Prendergast, et al. (2005), J Biomech 38(5): 1023-33.
Abstract: Glenoid component loosening is the major problem of total shoulder arthroplasty. It is possible that uncemented component may be able to achieve superior fixation relative to cemented component. One option for uncemented glenoid is to use porous tantalum backing. Bone ingrowth into the porous backing requires a degree of stability to be achieved directly post-operatively. This paper investigates the feasibility of bone ingrowth with respect to the influence of primary fixation, elastic properties of the backing and friction at the bone prosthesis interface. Finite element models of three glenoid components with different primary fixation configurations are created. Bone ingrowth into the porous backing is modelled based on the magnitude of the relative interface micromotions and mechanoregulation of the mesenchymal stem cells that migrated via the bonded part of the interface. Primary fixation had the most influence on bone ingrowth. The simulation showed that its major role was not to firmly interlock the prosthesis, but rather provide such a distribution of load, that would result in reduction of the peak interface micromotions. Should primary fixation be provided, friction has a secondary importance with respect to bone ingrowth while the influence of stiffness was counter intuitive: a less stiff backing material inhibits bone ingrowth by higher interface micromotions and stimulation of fibrous tissue formation within the backing.

Bone reconstruction: from bioceramics to tissue engineering
El-Ghannam, A. (2005), Expert Rev Med Devices 2(1): 87-101.
Abstract: Over the past 30 years, an enormous array of biomaterials proposed as ideal scaffolds for cell growth have emerged, yet few have demonstrated clinical efficacy. Biomaterials, regardless of whether they are permanent or biodegradable, naturally occurring or synthetic, need to be biocompatible, ideally osteoinductive, osteoconductive, integrative, porous and mechanically compatible with native bone to fulfill their desired role in bone tissue engineering. These materials provide cell anchorage sites, mechanical stability and structural guidance and in vivo, provide the interface to respond to physiologic and biologic changes as well as to remodel the extracellular matrix in order to integrate with the surrounding native tissue. Calcium phosphate ceramics and bioactive glasses were introduced more than 30 years ago as bone substitutes. These materials are considered bioactive as they bond to bone and enhance bone tissue formation. The bioactivity property has been attributed to the similarity between the surface composition and structure of bioactive materials, and the mineral phase of bone. The drawback in using bioactive glasses and calcium phosphate ceramics is that close proximity to the host bone is necessary to achieve osteoconduction. Even when this is achieved, new bone growth is often strictly limited because these materials are not osteoinductive in nature. Bone has a vast capacity for regeneration from cells with stem cell characteristics. Moreover, a number of different growth factors including bone morphogenetic proteins, have been demonstrated to stimulate bone growth, collagen synthesis and fracture repair both in vitro and in vivo. Attempts to develop a tissue-engineering scaffold with both osteoconductivity and osteoinductivity have included loading osteoinductive proteins and/or osteogenic cells on the traditional bioactive materials. Yet issues that must be considered for the effective application of bioceramics in the field of tissue engineering are the degree of bioresorption and the poor mechanical strength. The synthesis of a new generation of biomaterials that can specifically serve as tissue engineering scaffolds for drug and cell delivery is needed. Nanotechnology can provide an alternative way of processing porous bioceramics with high mechanical strength and enhanced bioactivity and resorbability.

Bone regeneration in extraction sites after immediate placement of an e-PTFE membrane with or without a biomaterial. A report on 12 consecutive cases
Dies, F., D. Etienne, et al. (1996), Clin Oral Implants Res 7(3): 277-85.
Abstract: The efficacy in restoring a buccal dehiscence after tooth extraction has been studied in 12 consecutive cases using guided bone regeneration with (6 patients) or without (6 patients) a biomaterial (DFDBA or Bio Oss) beneath an e-PTFE membrane. A correlation between the clinical impression of density at drilling time and the histological signs of bone formation has been evaluated too. The membrane was removed after 6 or 9 months and a biopsy was performed. Clinically, GBR was highly predictable for regeneration of the alveolar bone after tooth extraction with buccal dehiscence. The histology fully confirmed the clinical and radiographical results, showing bone formation in all cases with individual variations in the amount of bone formed. 6-month biopsies from the membrane sites had lamellar bone with large medullary spaces, while a good bone density was observed at 9 months. The membrane/biomaterial sites demonstrated mineralization and large amounts of allograft at 6 months. Thus, bone regeneration seems to take more time when grafting material is used.

Bone regeneration in osseous defects using a resorbable nanoparticular hydroxyapatite
Thorwarth, M., S. Schultze-Mosgau, et al. (2005), J Oral Maxillofac Surg 63(11): 1626-33.
Abstract: PURPOSE: This animal study examined the de novo bone formation in bony defects following the insertion of autogenous bone alone versus an injectable nanoparticle hydroxyapatite alone and in combination with 25% autogenous bone. The regenerative potentials of the tested materials were compared with each other. MATERIALS AND METHODS: A model with biological similarity to humans with regard to bone regeneration was a prerequisite for the transferability of the results to clinical practice. Therefore, the adult domestic pig was the animal of choice. A total observation period of 6 months was selected. Microradiographic and histologic evaluation of the bone specimens was completed at 8 defined times. RESULTS: Microradiography indicated mineralization rates in the 2 bone substitute groups that were not significantly lower than those found in the autogenous bone group. Histologically, there was suitable osseointegration and osteoconduction of the used material. Complete resorption of the nanoparticle hydroxyapatite had taken place after 12 weeks. CONCLUSIONS: It can be concluded that the evaluated nanoparticular hydroxyapatite met the clinical requirements for a bone substitute material within the limits of this experimental setting. Due to its microstructure, complete resorption took place during the course of this study.

Bone regeneration in standardized bone defects with autografts or bone substitutes in combination with platelet concentrate: a histologic and histomorphometric study in the mandibles of minipigs
Jensen, S. S., N. Broggini, et al. (2005), Int J Oral Maxillofac Implants 20(5): 703-12.
Abstract: PURPOSE: To evaluate the effect of the addition of platelet concentrate (PC) to autografts or bone substitutes on bone regeneration in standardized bone defects. MATERIALS AND METHODS: Three standardized bone defects were prepared in both mandibular angles of 12 adult minipigs. The defects were grafted with autograft, anorganic bovine bone, or synthetic beta-tricalcium phosphate (beta-TCP). PC was added to only 1 side. The animals were divided into 4 groups, which were sacrificed at 4 different time points (1, 2, 4, and 8 weeks) for histologic and histomorphometric analysis. The concentrations of platelets and growth factors were measured to identify correlation to the histologic and histomorphometric results. RESULTS: No correlation was found between platelet count in whole blood and platelet count in PC (r(p) = 0.36). Furthermore, no correlation could be demonstrated between the platelet count of the PC and the concentrations of PDGF-AB (r(p) = -0.27) and TGF-beta (r(p) = 0.34). There were no signs of a stimulating effect of PC on bone formation in combination with autografts or bone substitutes at any time point (P =.89). Addition of PC did not alter the pattern of graft degradation. DISCUSSION: The present study underlines the need for further investigation to identify the optimal concentrations of platelets and combinations of growth factors to achieve a predictable stimulatory effect on bone regeneration. One of the first steps to achieve this goal will be the development of a reliable method for the procurement of PC. CONCLUSION: PC had no impact on bone formation and graft degradation in standardized bone defects in the mandibles of minipigs.

Bone regeneration in the rat mandible with bone morphogenetic protein-2: a comparison of two carriers
Arosarena, O. A. and W. L. Collins (2005), Otolaryngol Head Neck Surg 132(4): 592-7.
Abstract: OBJECTIVE: To compare mandibular bone regeneration with bone morphogenetic protein-2 (BMP-2) delivered with two carriers: a hyaluronic acid polymer (HY), and a collagen carrier complexed with calcium hydroxyapatite and tricalcium phosphate (collagen/HA/TCP). STUDY DESIGN: Defects were created in the bilateral mandibular bodies of 16 Sprague-Dawley rats. The defects were filled with the HY carrier, the HY carrier loaded with BMP-2, the collagen/HA/TCP carrier, or the collagen/HA/TCP carrier loaded with BMP-2. Animals were euthanatized after 6 weeks, and the hemi-mandibles were analyzed histomorphologically. RESULTS: Specimens containing BMP-2 had significantly larger new bone and marrow volumes than control specimens. Specimens in the hyaluronan/BMP-2 group tended to have larger volumes of new bone and osteoid than collagen/HA/TCP/BMP-2 specimens, though these differences were not statistically significant. CONCLUSION: The HY and collagen/HA/TCP carriers had comparable efficacy for bone healing with BMP-2. SIGNIFICANCE: Bone morphogenetic proteins can be delivered with commercially available alloplasts as osteogenic bone substitutes for the repair of craniofacial bone defects. EBM rating: B-2.

Bone replacement grafts for periodontal regeneration
Minsk, L. (2005), Compend Contin Educ Dent 26(9): 676, 678, 680 passim.

Bone resorption around dental implants placed in grafted sinuses: clinical and radiologic follow-up after up to 4 years
Maiorana, C., D. Sigurta, et al. (2005), Int J Oral Maxillofac Implants 20(2): 261-6.
Abstract: PURPOSE: The long-term results of endosseous implants depend on the maintenance of bone support. The aim of this study was to evaluate radiologically bone resorption around dental implants placed in grafted sinuses after up to 4 years of function. MATERIALS AND METHODS: Between 1997 and 2001, augmentation of the maxillary sinus floor with alloplastic (Biostite) or xenogenic (Bio-Oss) materials was performed in 34 patients. RESULTS: Eighteen patients participated in the study. Twenty-six sinus augmentations were performed on these 18 patients, and they received 37 implants. The change in marginal bone level around the implants at the mesial side was 1 mm during the first year after the abutment connection, followed by an annual loss of 0.1 mm. The change in marginal bone level around the implants at the distal side was 1.1 mm during the first year after the abutment connection followed by an annual loss of 0.2 mm. DISCUSSION: The implant survival rate observed in this study is in line with data previously reported for patients treated with implants in the posterior maxilla without bone atrophy. The results for implants placed into sinuses grafted with Bio-Oss were similar to the results for implants placed in sinuses grafted with Biostite. CONCLUSION: Although this study involved a limited number of procedures, it confirmed that alloplastic and xenogenic materials can be reliable for bone regeneration in subantral cavities. The angular defects present both at the distal and mesial sides of the implants were comparable to those observed at implants placed in native bone.

Bone substitute with osteoinductive biomaterials--current and future clinical applications
Hotz, G. and G. Herr (1994), Int J Oral Maxillofac Surg 23(6 Pt 2): 413-7.
Abstract: In craniomaxillofacial surgery, possible indications for the use of osteo-inductive biomaterials are interposition in intraosseous defects, contour augmentation, and reconstruction of segmental defects. The experimental results in the field of bone morphogenetic protein (BMP) research within the last few years have shown that it is possible to combine osteoinductive proteins with suitable carrier materials to obtain new composite osteoinductive biomaterials. These carrier materials function as slow-delivery systems for BMP. By combination of BMP with different carrier materials such as various types of calcium phosphate ceramics, collagen or inactive collagenous bone matrix, and other organic and inorganic carriers, the biomaterial can be adapted to clinical demands in a wide range. In several experimental animal studies, we investigated nine different calcium phosphate ceramics and inactive rat bone matrix for their use as BMP carrier. All materials tested seem to be suitable carriers for BMP. The first clinical applications are discussed.

Bone tissue engineering evaluation based on rat calvaria stromal cells cultured on modified PLGA scaffolds
Wu, Y. C., S. Y. Shaw, et al. (2006), Biomaterials 27(6): 896-904.
Abstract: Using natural materials to coat the scaffolds used for tissue-engineered bone-repair techniques is expected to increase osteoblast adhesion to the scaffold and to express normal physiological function. To test this hypothesis, we therefore modified poly(dl-lactic-co-glycolic acid) (PLGA) substrate by coating it with natural biomaterial solutions of collagen, chitosan, or N-succinyl-chitosan, and then used these three combinations as scaffolds to evaluate their effects on osteoblast attachment, proliferation, and differentiation. The results demonstrated that the pore size of scaffolds ranging from 125-500mum did not affect the osteoblast phenotype; however, the surface modification of the scaffolds coated with these natural biomaterials did. Collagen increased cell attachment and proliferation, but chitosan and N-succinyl-chitosan decreased them. Chitosan and N-succinyl-chitosan increased differentiation, but collagen decreased it. These results provide us a new strategy for modifying microenvironments to increase osteoblast adhesion, proliferation, and differentiation on PLGA scaffolds, a strategy that might be useful for tissue regeneration.

Bone tissue engineering on amorphous carbonated apatite and crystalline octacalcium phosphate-coated titanium discs
Dekker, R. J., J. D. de Bruijn, et al. (2005), Biomaterials 26(25): 5231-9.
Abstract: Poor fixation of bone replacement implants, e.g. the artificial hip, in implantation sites with inferior bone quality and quantity may be overcome by the use of implants coated with a cultured living bone equivalent. In this study, we tested, respectively, amorphous carbonated apatite (CA)- and crystalline octacalcium phosphate (OCP)-coated discs for their use in bone tissue engineering. Subcultured rat bone marrow cells were seeded on the substrates and after 7 days of culture, the implants were subcutaneously implanted in nude mice for 4 weeks. After 7 days of culture, the cells had formed a continuous multi-layer that covered the entire surface of the substrates. The amount of cells was visually higher on the crystalline OCP-coated discs compared to the amorphous CA-coated discs. Furthermore, the amorphous CA-coated discs exhibited a visually higher amount of mineralized extracellular matrix compared to the crystalline OCP-coated discs. After 4 weeks of implantation, clear de novo bone formation was observed on all discs with cultured cells. The newly formed bone on the crystalline OCP-coated discs was more organized and revealed a significantly higher volume compared to the amorphous CA-coated discs. The percentage of bone contact with the discs was also significantly higher on the OCP-coated discs. Overall, the results suggest that a crystalline OCP coating is more suitable for bone tissue engineering than an amorphous CA coating.

Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering
Williams, J. M., A. Adewunmi, et al. (2005), Biomaterials 26(23): 4817-27.
Abstract: Polycaprolactone (PCL) is a bioresorbable polymer with potential applications for bone and cartilage repair. In this work, porous PCL scaffolds were computationally designed and then fabricated via selective laser sintering (SLS), a rapid prototyping technique. The microstructure and mechanical properties of the fabricated scaffolds were assessed and compared to the designed porous architectures and computationally predicted properties. Scaffolds were then seeded with bone morphogenetic protein-7 (BMP-7) transduced fibroblasts and implanted subcutaneously to evaluate biological properties and to demonstrate tissue in-growth. The work done illustrates the ability to design and fabricate PCL scaffolds with porous architecture that have sufficient mechanical properties for bone tissue engineering applications using SLS. Compressive modulus and yield strength values ranged from 52 to 67 MPa and 2.0 to 3.2 Mpa, respectively, lying within the lower range of properties reported for human trabecular bone. Finite element analysis (FEA) results showed that mechanical properties of scaffold designs and of fabricated scaffolds can be computationally predicted. Histological evaluation and micro-computed tomography (microCT) analysis of implanted scaffolds showed that bone can be generated in vivo. Finally, to demonstrate the clinical application of this technology, we designed and fabricated a prototype mandibular condyle scaffold based on an actual pig condyle. The integration of scaffold computational design and free-form fabrication techniques presented here could prove highly useful for the construction of scaffolds that have anatomy specific exterior architecture derived from patient CT or MRI data and an interior porous architecture derived from computational design optimization.

Bone tissue induction, using a COLLOSS-filled titanium fibre mesh-scaffolding material
Walboomers, X. F. and J. A. Jansen (2005), Biomaterials 26(23): 4779-85.
Abstract: Scaffold materials for bone tissue engineering often are supplemented with bone morphogenetic proteins (BMPs). In the current study we aimed to investigate COLLOSS, a bovine extracellular matrix product containing native BMPs. Hollow cylindrical implants were made, with a length of 10 mm, a 3 mm inner diameter, and a 5 mm outer diameter, from titanium fibre mesh. The central space of the tube was filled with 20 mg COLLOSS. Subsequently, these implants, as well as non-loaded controls, were implanted subcutaneously into the back of Wistar rats, with n=6 for all study groups. After implantation periods of 2, 8, and 12 weeks, tissue-covered implants were retrieved, and sections were made, perpendicular to the long axis of the tube. Histology showed, that all implants were surrounded by a thin fibrous tissue capsule. After 2 weeks of implantation, the COLLOSS material was reduced in size inside the loaded implants, but no bone-like tissue formation was evident. After 8 weeks, in two out of six loaded specimens, new-formed bone- and bone marrow-like tissues could be observed. After 12 weeks, this had increased to five out of six COLLOSS-loaded samples. The amount of bone-like tissue did not differ between 8 and 12 weeks, and on average occupied 15% of the central space of the tube. In the non-loaded control samples, only connective tissue ingrowth was observed. In conclusion, we can say that COLLOSS material loaded in a titanium fibre mesh tube, showed bone-inducing properties. The final efficacy of these osteo-inductive properties has to be confirmed in future large animal studies.

Bone tissue responses to surface-modified zirconia implants: A histomorphometric and removal torque study in the rabbit
Sennerby, L., A. Dasmah, et al. (2005), Clin Implant Dent Relat Res 7 Suppl 1: S13-20.
Abstract: BACKGROUND: Zirconia ceramics are biocompatible and have mechanical properties that make them suitable as materials for dental implants. Little is known about how surface modification influences the stability and bone tissue response to zirconia implants. PURPOSE: The objective of the investigation was to histologically and biomechanically evaluate the bone tissue response to zirconia implants with two different surface modifications in comparison with machined, nonmodified zirconia implants and oxidized titanium implants. MATERIALS AND METHODS: Threaded zirconia implants with a diameter of 3.75 mm with either a machined surface (Zr-Ctr) or one of two surface modifications (Zr-A and Zr-B) were manufactured. Oxidized titanium (Ti-Ox) implants 3.75 mm in diameter were also used. The implants were characterized with regard to surface topography using an interferometer. Twelve rabbits received 96 implants using a rotational scheme, two in each tibia and two in each femur. The implants in six rabbits were subjected to removal torque (RTQ) tests after a healing period of 6 weeks. The implants in the remaining six animals were removed en bloc for light microscopic analysis. Back-scatter scanning electron microscopic (BS-SEM) analyses were used to evaluate the state of the bone-implant interface at the modified zirconia implants after RTQ testing. RESULTS: The Ti-Ox and Zr-A implants showed the highest surface roughness, followed by the Zr-B implants and, finally, the Zr-Ctr implants. The nonmodified ZrO2 implants showed statistically significant lower RTQs than all other implants. No significant differences in bone-implant contact or bone area filling the threads were observed. BS-SEM showed intact surface layers of the surface-modified implants after RTQ testing and revealed fracture of the interface bone rather than a separation. CONCLUSION: The present study showed a strong bone tissue response to surface-modified zirconia implants after 6 weeks of healing in rabbit bone. The modified zirconia implants showed a resistance to torque forces similar to that of oxidized implants and a four- to fivefold increase compared with machined zirconia implants. The findings suggest that surface-modified zirconia implants can reach firm stability in bone.

Bone-implant contact at calcium phosphate-coated and porous titanium oxide (TiUnite)-modified oral implants
Xiropaidis, A. V., M. Qahash, et al. (2005), Clin Oral Implants Res 16(5): 532-9.
Abstract: BACKGROUND: Calcium phosphate (CP)-coated implants are usually referred to as having osteoconductive properties, whereas titanium implants with a native oxide layer are considered less osteoconductive. Often smooth titanium oxides (TOs) are compared to relatively rough CP structures. The objective of this study was to evaluate osteoconduction by comparing bone-implant contact at a relatively smooth, highly crystalline CP coating with a structured, porous TO (TiUnite)-modified surface. MATERIAL AND METHODS: Ten adult Hound Labrador mongrel dogs were used. Four titanium implants (Nobel Biocare) with CP-coated (2) or TO-modified (2) surfaces were installed 12 weeks following mandibular premolar and molar teeth extraction. The implants were alternated within and between jaw quadrants in consecutive animals. Mucosal flaps were advanced and sutured leaving the implants in a submerged position. The animals were injected with fluorescent bone labels at 3 and 4 weeks postsurgery, and pre-euthanasia to monitor progress of bone formation. The animals were euthanized at 8 weeks postsurgery and block biopsies were prepared for histologic and histometric analysis. RESULTS: There were no remarkable differences in bone formation and apparent bone-implant contact comparing the TO-modified and CP-coated surfaces. However, the measured average bone-implant contact was 71% and 57% (P=0.027) for TO-modified and CP-coated implants, respectively. CONCLUSIONS: We conclude that the TO surface exhibits osteoconductive properties exceeding that of the CP surface. One or several of the chemical and physical properties of the TO surface may result in the remarkable bone formation along its surface. This study indicated that crystallinity and/or chemistry may be important.

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Last Modified: 8 February 2006