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Porous hydroxyapatite as a bone graft substitute in alveolar ridge augmentation: a histometric study.

Following bilateral alveolectomy, the ridge form was restored in 10 dogs with blocks of porous HA matrix and bicortical iliac autografts. The specimens were retrieved after 11 to 17 months and undecalcified sections were prepared for microscopy and histometry. Within the HA implants, bone ingrowth extended throughout the pores. This bone appeared mature and well vascularized. The autografts united to the mandible. However bone ingrowth into the cancellous spaces of the grafts was minimal or absent. Measurement of implant and graft cross-sectional areas showed the maintenance of alveolar ridge form to be equally permanent for the 2 materials over the 1.5 year duration of the study. The implant specimens were composed of 43.1% HA matrix, 45.2% bone and 11.7% soft tissue. The HA matrix had a surface area averaging 9.3 mm2/mm3 that was 91.1% covered with bone ingrowth. Although this study supported the thesis that a porous HA matrix can function as a bone graft substitute, it is noted that the unyielding nature of the implant blocks, compared to granules, requires a solution to the challenge of long-term denture support without ulceration before it can be used with clinical confidence.

Alveolar Ridge Augmentation↗

Histological study on sinus lift grafting by Fisiograft and Bio-Oss.

The work aims to provide a histological investigation of Fisiograft, a PLA/PGA copolymer, used as filler for bone defects in humans. The study was performed on biopsies of sinus lifts where Bio-Oss and Fisiograft gel were applied as graft material. Bone regeneration was satisfactory in all sinus lifts, even when Fisiograft was applied alone. Due to remarkable osteoclast activity, Bio-Oss granules were cleared from the majority of biopsy cores. At histology, Fisiograft gel appeared as globes enveloped by fibroblasts, displaying an epithelial-like cell appearance. Due to its solubility in solvents, undegraded Fisiograft (recorded for 7 months or more) did not stain whereas degraded Fisiograft stained positive. The loose connective tissue, that surrounded Fisiograft and bone contained isolated mastocytes. Bone grew inside the loose connective and often reached the surface of Fisiograft by intervening cells. The results seem to indicate that Fisiograft may be considered both a polymer useful for fastening bone substitutes inside a defect and in addition a material capable of prompting bone regeneration, with or without the use of a bone substitute. In addition to space-former and space-maintainer functions, Fisiograft shows potential bone stimulation function, which may be labelled as osteopromotive capability.

Autoradiography↗

[Osseous defect regeneration using autogenous bone alone or combined with Biogran or Algipore with and without added thrombocytes. A microradiologic evaluation].

In addition to autogenous bone, a variety of bone substitute materials is used to regenerate bony defects. The aim of the study was to evaluate the reossification of critical size defects in the os frontale of adult pigs ( n=16) with microradiography. The defects were filled randomly with autogenous bone or the bone substitute materials Algipore and Biogran each combined with a defined quantity of autogenous bone. Additionally, platelet-rich plasma (PRP) was added in defined quantities (0.5 ml) in two different concentrations (4-fold and 6.5-fold). At 2, 4, 12, and 26 weeks four animals were sacrificed and the osseous regeneration documented by quantitative evaluation of the microradiographic findings. Microradiographic results in the autogenous bone group showed an earlier PRP concentration-dependent mineralization. Over the whole observation period the peak value of autogenous bone as filler alone could not be reached in both PRP groups. Using Algipore, no accelerated effect of mineralization however could be observed. In our study, Biogran proved to be a defect filler only partially suitable for bony defect healing, no matter whether PRP was added or not.

Alginates↗

Coralline porous hydroxyapatite as a bone graft substitute in orthognathic surgery: 24-month follow-up results.

A 24-month postsurgical follow-up evaluation was performed on 49 patients (20 males and 29 females; mean age 26 years [range 9 to 52 years]) who had undergone orthognathic surgery in which coralline porous block hydroxyapatite (PBHA) was used as a bone graft substitute. Followup ranged from 23 to 45 months (average 27 months). One surgeon implanted all 215 blocks: 189 blocks to the maxilla, 19 blocks to the mandible, and seven blocks to the midfacial region. Of the 215 implants, 135 were positioned directly adjacent to the maxillary sinus. Nine patients had postsurgical complications: three developed sinusitis, which was treated with antibiotics and decongestants, four had midpalatal implants exposed intraorally during surgery that later required removal, one had a slight displacement of a mandibular implant that has remained in place, and one had an interdental implant exposed that was recontoured and covered with tissue. At the 24-month followup or later, only one of the 49 patients had complications or symptoms associated months postsurgery. These results strongly support the use of coralline PBHA along with bone plate fixation to provide predictable stability in orthognathic surgery.

Adolescent↗

In vivo investigations on composites made of resorbable ceramics and poly(lactide) used as bone graft substitutes.

Porous composites made of poly(L, DL-lactide) (PLA) and alpha-tricalcium phosphate (alpha-TCP) or the glass ceramic, GB14N, respectively, were investigated in a loaded implant model in sheep. Six, 12 and 24 months after implantation histological and biomechanical evaluation were performed and compared to autogenous bone transplants. No significant differences were observed between the composites. After 6 months, the interconnecting pores of the alpha-TCP-composite and the GB14N-composite were filled with newly formed bone (14 +/- 5% or 29 +/-15% of the implant, respectively) and soft tissue (30 +/-9% or 21 +/-12% of the implant, respectively). Only a mild inflammatory response was observed. The reaction was similar after 12 months. However, after 24 months a strong inflammatory reaction was seen. The newly formed bone was partly osteolytic. The adverse reaction occurred simultaneously to a significant reduction of the PLA component. The histological results were reflected by the biomechanical outcomes. Both composites showed compression strengths in the range of the autologous bone graft until 12 months of implantation. After 2 years, however, the strengths were significantly decreased. It is concluded that the new composites cannot yet be used for clinical application. An improvement in biocompatibility might be reached by a better coordination of the degradation times of the polymer and the ceramic component.

Absorbable Implants↗

Calcium sulfate used as bone graft substitute in acetabular fracture fixation.

The purpose of this study was to determine the natural history of calcium sulfate pellets implanted during acetabular fracture surgery. The study group consisted of patients sustaining an acetabular fracture with intraarticular comminution or marginal impaction or both in whom calcium sulfate pellets were implanted in lieu of autologous bone graft. Between 1997 and 1999, 32 fractures were treated. Followup adequate to delineate pellet outcome, including radiographs and computed tomography, was obtained in 31 patients. Evaluation of plain radiographs showed that the calcium sulfate pellets became undifferentiated from the surrounding bone at an average of 7 weeks postoperatively. In no case was a residual bony deficit seen. Computed tomography analysis showed that in 22 patients, the pellets essentially had been (> 90%) replaced by bone and in four patients, the majority (> 50%-90%) of the pellets had been replaced by bone. However, in five patients, less than 50% of the pellets had been replaced by bone, including one showing no bony replacement. The common finding in patients with an extensive residual deficit was direct communication of the pellets with the joint space shown on the postoperative computed tomography scan. Patients with the best results had complete containment of the pellets within bone. Therefore, it seems that implanted calcium sulfate pellets in contact with joint synovial fluid are at risk for resorption without significant bony response. If calcium sulfate pellets are to be implanted in a periarticular location, complete bony containment is desirable. Evaluation of the periacetabular bony response requires computed tomography scans, as plain radiographs are inadequate for this purpose.

Acetabulum↗

[Epoxide acrylate maleic resin and hydroxyapatite composite material as a bone graft substitute in surgical correction of orbital reconstruction].

This paper illustrates the results of surgical correction in 11 cases with orbital deformities such as periorbital deficiency after orbitotomy for retinoblastoma and orbital malposition after facial trauma. EH composite material, mixture of hydroxyapatite and epoxide acrylate maleic resin in constant proportion, was used as a good bone graft substitute in all 11 cases. This material was easier to be molded during surgery, safe to human body, had no toxic effects, no irritation and no implant-related complications. The early results obtained in these patients are encouraging.

Adolescent↗

Characterization of osteoblast-like behavior of cultured bone marrow stromal cells on various polymer surfaces.

The creation of novel bone substitutes requires a detailed understanding of the interaction between cells and materials. This study was designed to test certain polymers, specifically poly(caprolactone) (PCL), poly(D,L-lactic-CO-glycolic acid) (PLGA), and combinations of these polymers for their ability to support bone marrow stromal cell proliferation and differentiation. Bone marrow stromal cells were cultured from New Zealand White rabbits and were seeded onto glass slides coated with a thin layer of PCL, PLGA, and combinations of these two polymers in both a 40:60 and a 10:90 ratio. Growth curves were compared. At the end of 2 weeks, the cells were stained for both matrix mineralization and alkaline phosphatase activity. There was no statistically significant difference in growth rate of the cells on any polymer or polymer combination. However, there was a striking difference in Von Kossa staining and alkaline phosphatase staining. Cells on PCL did not show Von Kossa staining or alkaline phosphatase staining. However, in the 40:60 and 10:90 blends, there was both positive Von Kossa and alkaline phosphatase staining. These data indicate that PCL alone may not be a satisfactory material for the creation of a bone substitute. However, it may be used in combination with PLGA for the creation of a bone substitute material.

Animals↗

Calcium phosphate coatings for medical implants.

In surgical disciplines where bone has to be repaired, augmented or improved, bone substitutes are essential. Although bone banks, such as Eurotransplant, are founded to supply such substitutes, natural bone is not always adequate. For example, frequently these so-called bone grafts resorb after implantation (1). Further, they cannot be used for joint and tooth replacement, and recently worries have been raised about the transfer of infectious diseases. Therefore, interest has dramatically increased in the use of synthetic materials for replacement of lost or damaged bone tissue. The generic name of these tissue alternatives is biomaterials. A special class of these biomaterials is composed of metallic devices with coatings to improve bone bonding. These specialized coatings used to improve the metallic implant are the topic of this paper.

Adhesiveness↗

Gel casting of resorbable polymers. 2. In-vitro degradation of bone graft substitutes.

Gel cast microporous materials produced from: slow resorbing, poly(L-lactide); fast resorbing, 50:50 poly(DL lactide coglycolide); and blends of these polymers have been characterized by weight loss, compression testing and thermal analysis after immersion in phosphate buffered saline (37 degrees C, pH 7.4) for times up to 6 months. Increasing weight loss and reduction in compressive properties with immersion time were measured. Blending reduces the rate of weight loss and material shrinkage relative to the copolymer. Thermal analysis of degraded samples revealed evidence of reorganization of the crystalline phase in poly(L-lactide) and a crystalline component in the 50:50 copolymer, estimated at 5-7% of the original material content, which is probably responsible for gel formation. Thermograms of the blend are effectively a superposition of thermograms of the individual components. Gel casting shows potential for varying the resorption rate, form stability and compressive properties of micro/macroporous bone graft substitutes.

Biocompatible Materials↗

Coralline hydroxyapatite bone-graft substitutes in a canine diaphyseal defect model. Radiographic-histometric correlation.

Radiographic and histometric evaluation of a new form of bonegraft substitute derived from reef-building sea coral was performed in a canine diaphyseal defect model. Comparably sized blocks of this material and iliac crest autograft were placed into bilateral surgically created cortical windows in the distal radial diaphyses of 14 dogs. Representative graft specimens of both types underwent densitometric radiography and harvesting at 3, 6, 12, 24, and 48 months. Histometric analysis of implant specimens revealed satisfactory union and native osseous ingrowth at all time intervals. Graft specimens exhibited adequate union with scant host bone ingrowth at three months, but subsequent progressive appositional closure of cancellous spaces during the ensuing 45 months. Volume fraction and mean width of host bone remained stable in the implants but increased in the grafts due to neocortex formation. Stereologic distribution of bone was homogeneous in both implant and graft specimens, and no evidence for biodegradation of the former was observed. Corrected transmission density determinations accurately reflected these differences but correlated significantly with volume fractions and tissue widths of bone and soft tissue only in the autografts. These results support the successful early application of coralline hydroxyapatite bone graft substitutes as an alternative to autogenous grafting in the clinical setting and emphasize the potential role of noninvasive densitometric techniques in monitoring the incorporation of bone-graft materials.

Absorptiometry, Photon↗

A newly designed vertebral replacement implant to reconstruct the thoracolumbar spine anteriorly.

Calcium phosphate compounds are becoming of increasingly great importance in the field of biomaterials and, in particular, as bone substitutes. In this way donor-side morbidity can be avoided. A type A lesion of the vertebral body can be the reason of a neurological deficit, requiring a corpectomy by means of an anterior approach, tricortical bone grafting and internal stabilization to get a fusion over time. It is our aim to introduce in this study a newly designed vertebral replacement device, tested in an animal model, using domestic pigs. Two biomaterials, Cementek and Biobon were primarily macroscopically and microscopically evaluated, using a critically sized bone defect of a vertebral body and compared with autologous bone grafts. The final tests consisted of two groups of four animals. A corpectomy at the level of L4 was created and stabilized by means of the newly designed vertebral replacement implant. Autologous bone grafts were applied in one group of animals and Cementek in the other to fill the remaining space. Fusion was studied using anteroposterior and lateral radiographs, followed by a computer tomography. The biocompatibility of the biomaterials and autologous bone grafts were in order of: Cementek > autologous bone grafts > Biobon. In the final tests after a six months period, a fusion was diagnosed in four cases, two delayed unions, and two obvious non-unions. An analysis of the failures in this animal study can possibly clarify the shortcomings of this concept. Perhaps, subtle changes of the design combined with other synthetic bone substitutes can possibly improve the fusion rate in the near future.

Animals↗

Healing of experimentally created defects: a review.

Within cranio-maxillofacial surgery and orthopedic surgery a bone graft or a bone substitute is required to recontour or assist bony healing in repair of osseous congenital deformities, or in repair of deformity due to trauma or to surgical excision after elimination of osseous disease processes exceeding a certain size. An autogenous bone graft is the optimal material of choice, however its use is problematic due to donor site morbidity, sparse amounts and uncontrolled resorption. Immunological responses and risk of viral contamination of allogenous and xenogenous bone materials make the use of these materials questionable. Healing and degradation of alloplastic materials are inconsistent with subsequent restricted use. The principle of guided tissue regeneration excluding soft tissue cells from a certain area is not alone sufficient to insure complete bony healing. Recombinant bone morphogenetic proteins have with success been added as adjuncts to already known biomaterials. In the future, inductive materials together with a suitable carrier and a biodegradable membrane may be the choice of bone substitute used within cranio-maxillofacial and orthopaedic surgery.

Animals↗

Implantation of octacalcium phosphate (OCP) in rat skull defects enhances bone repair.

Synthetic octacalcium phosphate (OCP) enhances bone formation if implanted into the subperiosteal region of murine bone. Such implanted OCP may be resorbed and replaced by bone with time. We hypothesized that OCP could be used as an effective bone substitute. To test this hypothesis, we designed the present study to investigate if bone repair in a rat skull defect is enhanced by the implantation of OCP. Rats were divided into two groups: OCP-treated animals and untreated controls. Six rats from each group were fixed at 4, 12, and 24 weeks after implantation. A full-thickness standardized trephine defect was made in the parietal bone, and synthetic OCP was implanted into the defect. After being examined radiographically, the specimens were decalcified and processed for histology. OCP implantation significantly promoted bone repair compared with the controls. A statistical analysis showed an increase in the area of radiopacity within the skull defect between week 4 and week 12. Histologically, bone was formed on the implanted OCP and along the defect margin at week 4. At week 12, the implanted OCP was surrounded by newly formed bone. At week 24, the defect was almost completely filled with bone. In the control, bone formation was observed only along the defect margin. The present results demonstrate that OCP could be used as an effective bone substitute.

Animals↗

Symposium "Implantable Materials in Facial Aesthetic and Reconstructive Surgery: Biocompatibility and Clinical Applications". American Society of Maxillofacial Surgeons. Montreal, Quebec, October 6, 1995.

On October 6, 1995, the American Society of Maxillofacial Surgeons sponsored a 1-day symposium entitled "Implantable Materials in Facial Aesthetic and Reconstructive Surgery: Biocompatibility and Clinical Applications." The symposium examined issues relating to the biocompatibility and clinical role of alloplastic materials commonly used for facial bone and soft-tissue replacement and augmentation. It provided a forum for the interaction of basic scientists, clinicians, and manufacturers. Clinical and laboratory data concerning a variety of implantable materials were presented and discussed. The program consisted of three parts. The first session was designed to provide historical and scientific background as well as perspective on legal issues surrounding the use of implantable biomaterials. The second session involved the presentation of clinical data on bone and bone substitutes for augmentation of the facial skeleton. The third session was devoted to clinical reports of bone and bone substitutes used for the reconstruction of cranial vault and cranial base skull defects.

Biocompatible Materials↗

A histological evaluation on self-setting alpha-tricalcium phosphate applied in the rat bone cavity.

This study aimed to elucidate the biological effects of a self-setting tricalcium phosphate bone substitute (BIOPEX) applied in rat femoral cortical bone cavities. Narrow penetrations through the cavity and bone marrow were prepared to obtain cellular sources. In the experimental group at day 1, a thin cell layer intruded into a narrow space between the grafted BIOPEX and the bottom of the cavity. From days 5 to 10, a range of tartrate-resistant acid phosphatase (TRAPase)-reactive osteoclasts accumulated on the surface of the BIOPEX facing the bottom of the cavity, whilst many alkaline phosphatase (ALPase)-positive osteoblasts were localized on the bone surface opposing the BIOPEX. However, at day 20, osteoblasts were localized neighboring the osteoclasts on the BIOPEX, and deposited bone matrices onto this material, implying a coupling between osteoclasts and osteoblasts. At days 30 and 40 post-operation, small remnants of BIOPEX particles were present in the new bone with a profile of compact bone. Thus, BIOPEX is resorbed by osteoclasts, and succeeded by osteoblastic bone apposition with a coupling of osteoclasts and osteoblasts at the later stage. In conclusion, the use of BIOPEX provides adequate bone regeneration with the profile of compact bone.

Acid Phosphatase↗

Biotechnology and bone graft substitutes.

Trauma, disease, developmental deformities, and tumor resection frequently cause bone defects that seriously challenge the skills of orthopedic and maxillofacial surgeons. Currently, repairing osseous deficiencies involves various medical surgical techniques, including autogenous grafts, allografts, internal and external fixation devices, electrical stimulation, and alloplastic implants. The existing technology, though effective in many cases, still is beset with numerous difficulties and disadvantages. A critical need for improved treatment methods exists today. Biotechnology now provides access to new bone repair concepts via administration of protein growth and morphogenic factors. Implantable device and drug delivery system technologies also have advanced. The converging biopharmaceutical, device, and delivery technologies represent an opportunity to improve the quality of health care for individuals with orthopedic and maxillofacial deficiencies. This report reviews current concepts in fracture healing and bone repair and examines existing treatment modalities. It also addresses novel protein drugs that stimulate osseous regeneration and delivery systems for these drugs.

Amino Acid Sequence↗