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New blood vessel formation and expression of VEGF receptors after implantation of platelet growth factor-enriched biodegradable nanocrystalline hydroxyapatite.

Vascular endothelial growth factor (VEGF) plays a key role for the interaction of osteoblasts and endothelial cells and, therefore, is an important factor for the osteointegration of bone substitutes. The aim of the current work was to study the effects of platelet growth factors (PLF) on new blood vessel formation and VEGF-receptors expression pattern in bone defects filled with nanocrystalline hydroxyapatite (HA) paste in miniature-pigs. Conventional histology, RT-PCR for VEGF and receptors mRNA, Western blot analysis, immunohistochemical staining and quantitative assessment of newly formed vessels was performed. HA enriched with platelet growth factor (HA/PLF+) led to an up-regulation of VEGF-R1 synthesis, a slightly enhanced number of newly formed vessels with higher sprouting activity compared with HA without PLF (HA/PLF-) filling defects. These observation are most likely attributable to a stimulating effect of TGF-ss from the platelet factor on VEGF expression in osteoblasts.

Animals↗

Mechanical properties and histological evaluation of sintered beta-Ca2P2O7 with Na4P2O7.10H2O addition.

The ultimate goal of implantation of biomaterials in the skeleton is to reach full integration of the non-living implant with the living bone. The biomaterial can be used much as a bone graft, resorbing or dissolving as bone growth occurs, and the end result is a new remoulded bone. Calcium pyrophosphate, Ca2P2O7, is one of the intermediate products of bone mineralization. beta-Dicalcium pyrophosphate (beta-DCP) doped with certain amounts of Na4P2O7.10H2O was prepared as the developed material. Na4P2O7.10H2O was used as a liquid-phase additive to improve the sintering process and promote physiological bioresorbability. Compressive strength and four-point bending strength were measured by the Bionix test system 858. The mechanical strength of the sintered beta-DCP increased with the addition of Na4P2O7.10H2O up to 5 wt%, but thereafter decreased. The microstructure and crystal structure were analysed by the techniques of SEM, EPMA, TEM and XRD. The relationship between the mechanical strength of the sintered bioceramics and the Na4P2O7.10H2O dopant was examined in terms of the presence of NaCa(PO3)3, grain growth and abnormal grain coalescence while the dopant increased. Preliminary in vivo evaluation was studied by rabbit femur condyle implantation. There was no inflammation or any toxic sign during the experimental period. The histological section of intraosseous implantation revealed that the new bone deposited directly on the surface of the material in the fourth week after operation. The implant gradually decreased in volume and was replaced by the surrounding regenerated bone in the rabbit condyle in vivo environment. The results led us to conclude that the developed material has great potential as a biodegradable bone substitute.

Animals↗

Hydroxylapatite blocks and particles as bone graft substitutes in orthognathic and reconstructive surgery.

A three-year clinical evaluation of 98 patients in whom dense hydroxylapatite in particle and block form had been placed in facial contour defects and osteotomy sites, and in cystic and reconstructive defects, alone or with autogenous bone, was conducted. The results indicate that the implants were effective in reducing operating time and potential for infection and relapse, as well as in reducing or eliminating the necessity of a donor site. The clinical response was excellent, and complications with both forms were minor, generally related to lack of initial fixation or failure to use autogenous bone in specific situations.

Bone Transplantation↗

Complications of iliac crest graft and bone grafting alternatives in foot and ankle surgery.

The ability to harvest iliac crest bone is a well-established skill in the surgical armamentarium of the orthopedic surgeon. As with any surgical procedure, this operation has its own set of complications. The surgeon must be aware of these potential problems in an effort to avoid them when possible. Other autologous sites for bone harvest are available to the surgeon, and s/he should be aware of these in terms of location, limitations of use, harvest technique, and potential pitfalls. The foot and ankle surgeon almost always needs less bone graft than our colleagues in spine surgery or joint revision surgery, so these other sites may be more suitable than the iliac crest for obtaining bone graft. Nonautogenous alternatives are becoming increasingly available to the orthopedist as a way to decrease morbidity and operating times. Scranton recently published an article about his success with several different bone substitute products that are used in foot and ankle reconstructive cases. As these options become more varied, it becomes more difficult to know which product to select. Understanding the biology of bone grafting with respect to osteoconduction, osteoinduction, and osteogenesis provides the surgeon with the knowledge that is needed to make an informed choice when selecting a bone grafting option. Before choosing an alternative graft material, the surgeon should also investigate how the graft material has performed in cases similar to his or her patient's needs. In the future, with continued research, the fields of tissue engineering and gene therapy will provide even better options for nonautogenous bone graft material.

Ankle Joint↗

Biomaterial challenges and approaches to stem cell use in bone reconstructive surgery.

As life expectancy increases, so does the need to treat large bone defects. New biomaterials combined with osteogenic cells are now being developed as an alternative to autogenous bone grafts. The goal is to make the stem cells adhere to the scaffold, and then grow to differentiate into functional osteogenic cells and organize into healthy bone as the scaffold degrades. Decisive improvements have been made in the fields of stem cell biology, 3-D scaffold fabrication and tissue engineering, but the ideal bone substitute that fulfils all functional and safety requirements has yet to be developed.

Biocompatible Materials↗

Repairing holes in the head: a history of cranioplasty.

Cranioplasty is almost as ancient as trephination, yet its fascinating history has been neglected. There is strong evidence that Incan surgeons were performing cranioplasty using precious metals and gourds. Interestingly, early surgical authors, such as Hippocrates and Galen, do not discuss cranioplasty and it was not until the 16th century that cranioplasty in the form of a gold plate was mentioned by Fallopius. The first bone graft was recorded by Meekeren, who in 1668 noted that canine bone was used to repair a cranial defect in a Russian man. The next advance in cranioplasty was the experimental groundwork in bone grafting, performed in the late 19th century. The use of autografts for cranioplasty became popular in the early 20th century. The destructive nature of 20th century warfare provided an impetus to search for alternative metals and plastics to cover large cranial defects. The metallic bone substitutes have largely been replaced by modern plastics. Methyl methacrylate was introduced in 1940 and is currently the most common material used. Research in cranioplasty is now directed at improving the ability of the host to regenerate bone. As modern day trephiners, neurosurgeons should be cognizant of how the technique of repairing a hole in the head has evolved.

Animals↗

Implant treatment in combination with lateral augmentation of the alveolar process: a 3-year prospective study.

BACKGROUND: In patients in whom the height of the alveolar process is adequate but the crest is too narrow to host an implant, lateral augmentation is required. Such augmentations have mostly been performed using autogenous bone blocks secured to the buccal surface. An alternative to autogenous bone may be bovine hydroxyapatite (Bio-Oss, Geistlich Pharma AG, Wolhusen, Switzerland) or other bone substitutes. PURPOSE: The aim of this study was to evaluate the clinical and radiographic outcome of dental implants inserted after lateral augmentation of too narrow alveolar processes with a combination of bovine hydroxyapatite (Bio-Oss) and autogenous bone. METHODS: Thirty patients (14 males and 16 females) with a mean age of 41.6 years fulfilled the inclusion criteria. Twenty-nine augmentation sites with a total of 74 implants could be followed for 3 years. RESULTS: Three implants were lost; these were lost before loading (at the abutment operation). The survival rate was 95.9%. The mean marginal bone loss during the 3-year observation period was 0.3 +/- 0.2 mm. CONCLUSIONS: A 50/50 combination of Bio-Oss and autogenous bone chips stabilized with Tisseel (Baxter AG/Duo Quick AG, Vienna, Austria) was useful for lateral augmentation of the alveolar crest. Lateral grafts with Bio-Oss, autogenous bone, and Tisseel made it possible to achieve good implant stability and high implant survival results. The bone level changes adjacent to the implants were the same as in nongrafted cases.

Adolescent↗

Peripheral quantitative computed tomography in evaluation of bioactive glass incorporation with bone.

This laboratory study examined the feasibility of non-invasive, in vivo peripheral quantitative computed tomography (pQCT) method in evaluation of bioactive glass incorporation with bone. An intramedullary defect model of the rat tibia was applied. The defect was filled with bioactive glass microspheres (diameter of 250-315 microm) or was left to heal without filling (empty controls). The results of the pQCT analysis were compared with those of histomorphometry. In the control defects, there was a good correlation (r2 = 0.776, p < 0.001) between the pQCT density of the intramedullary space and the amount of new bone measured by histomorphometry. In the defects filled with bioactive glass, the use of thresholding techniques of the applied pQCT system (Stratec XCT Research M) failed in separation of new bone formation and bioactive glass particles. However, detailed analysis of the pQCT attenuation profiles showed time-related changes which well matched with the histomorphometric results of new bone formation both in control and bioactive glass filled defects. The biphasic pQCT attenuation profiles of bioactive glass filled defects could be separated into two distinct peaks. In statistical analysis of various variables, the center (i.e. the value of attenuation) of the major attenuation peak was found to be the most significant indicator of the incorporation process. The center of the peak initially decreased (during the first 4 weeks of healing) and thereafter increased. These two phases probably reflect the primary resorption and reactivity of the bioactive glass microspheres in vivo followed by secondary new bone formation on their surfaces. Based on these results, pQCT-method seems to be suitable for in vivo follow-up of the bioactive glass incorporation processes. Although the imaging technique is not able to discriminate the individual microspheres from invading new bone unambiguously, the attenuation profiling seems to give adequate information about the state of the incorporation process. This information may help to establish non-invasive imaging techniques of synthetic bone substitutes for preclinical and clinical testing of their efficacy.

Animals↗

[Simple bone cysts of the calcaneus. Differential diagnosis and therapy].

Fifty-two calcaneal simple bone cysts from our clinic were evaluated. The lesions had a pathognomonic radiologic appearance and diagnosis was histologically confirmed in all operatively treated cases. Four cases presented with pathological fractures, three of which were treated by open reduction internal fixation and bone grafting, while one was treated nonoperatively. In addition, six patients with large cysts without apparent fracture but spontaneous pain were treated by curettage and subsequent autogenous bone grafting or calcium phosphate cement filling, and there were no recurrences. The majority of cysts (42 of 52) were however asymptomatic and thus followed up nonoperatively. This review reports on one of the largest series of cysts in this location. The results indicate that nonoperative management is justified in most asymptomatic cases. However, the potential risk of fracture as indicated by four fractured calcaneal cysts in this series suggests that large cysts should be clinically monitored and that operative intervention is useful in all symptomatic cases to prevent pathologic fractures. In the latter cases, curettage and bone grafting as well as the use of bone substitute material yielded uniformly good results.

Adolescent↗

Unicameral bone cysts.

Unicameral, or solitary, bone cysts are unusual tumors seen in the ends of long bones in skeletally immature persons. The etiology of these lesions is poorly understood. Various hypotheses have included dysplastic processes, synovial cysts, and abnormalities in the local circulation. Most patients present with a nondisplaced pathologic fracture, but occasionally cysts are found incidentally. Plain radiographs typically show a symmetric lesion with cortical thinning and expansion of the cortical boundaries. Once diagnosed, unicameral bone cysts continue to be a treatment dilemma. Traditional methods, such as prednisolone therapy, usually involve multiple anesthetics and injections and are associated with high recurrence rates. Major surgical procedures, such as wide exposure, curettage, and bone grafting, may be somewhat more effective, but still carry with them significant morbidity and recurrence rates. Newer techniques involving percutaneous grafting with allograft or bone substitutes or a combination of the two are promising in light of their low complication rate and lower reoperation rate.

Anti-Inflammatory Agents↗

Role of scaffold internal structure on in vivo bone formation in macroporous calcium phosphate bioceramics.

Purpose of this study was the analysis of the role of density and pore interconnection pathway in scaffolds to be used as bone substitutes. We have considered 2 hydroxyapatite bioceramics with identical microstructure and different macro-porosity, pore size distribution and pore interconnection pathway. The scaffolds were obtained with two different procedures: (a) sponge matrix embedding (scaffold A), and (b) foaming (scaffold B). Bone ingrowth within the two bioceramics was obtained using an established model of in vivo bone formation by exogenously added osteoprogenitor cells. The histological analysis of specimens at different time after in vivo implantation revealed in both materials a significant extent of bone matrix deposition. Interestingly enough, scaffold B allowed a faster occurrence of bone tissue, reaching a steady state as soon as 4 weeks. Scaffold A on the other hand reached a comparable level of bone formation only after 8 weeks of in vivo implantation. Both scaffolds were well vascularised, but larger blood vessels were observed in scaffold A. Here we show that porosity and pore interconnection of osteoconductive scaffolds can influence the overall amount of bone deposition, the pattern of blood vessels invasion and finally the kinetics of the bone neoformation process.

Animals↗

A 5-year prospective follow-up study of implant-supported fixed prostheses in patients subjected to maxillary sinus floor augmentation with an 80:20 mixture of bovine hydroxyapatite and autogenous bone.

BACKGROUND: Prospective long-term follow-up studies evaluating the use of bone substitutes to enable dental implant placement and integration are rare. PURPOSE: This study was undertaken to evaluate the survival rate of dental implants placed 6 months after maxillary sinus floor augmentation using a mixture of 80% bovine hydroxyapatite (BH) and 20% autogenous bone (AB). MATERIAL AND METHODS: Twenty patients subjected to 30 maxillary sinus floor grafting procedures using fibrin glue and an 80:20 mixture of BH and AB to enable placement of dental implants 6 months later were followed for 5 years of functional loading. Clinical and radiographic examinations of the grafts and implants were performed. RESULTS: After 5 years of functional loading with fixed bridges, 15 of 108 implants had been lost, giving a cumulative survival rate of 86%. The mean marginal bone loss after 5 years was 1.3 +/- 1.1 mm. CONCLUSION: Grafting of the maxillary sinus with a mixture of BH and AB and later placements of turned implants could be performed with predictable long-term results. All but one of the patients who were observed had functional fixed bridges after 5 years of functional loading.

Aged↗

Bovine-HA spongiosa blocks and immediate implant placement in sinus augmentation procedures. Histopathological and histomorphometric observations on different histological stainings in 10 consecutive patients.

Bovine mineral spongiosa block (B-SB) was used as a bone substitute in sinus augmentation procedures in 10 consecutive patients. Implants were placed during the same session. The purpose of this study was to histopathologically examine the healing of the grafted site around the implants at 12 months. Radiographic follow-up showed apparent bone apposition in the augmented area around the implants. Clinically, all 36 implants were stable and integrated with the surrounding tissue. Histopathologically, new bone formation was evident in all specimen hard tissue cores. Hydroxyapatite particles were present in direct contact with the remodeled osseous tissue. Mallory trichrome staining showed different stages of mineralization and maturation of the newly formed bone around the grafted mineral particles. Morphometric evaluation of Picrosirius red stained slides under polarized light microscopy was performed at the peripheral/external and deep section slides of all specimens. The average bone area fraction was 34.2%, with a 1 : 5.4 mean lamellar/woven bone ratio at the peripheral side and 53.0%, with 1 : 2.5 mean ratio at the deep side. The differences of both parameters between the two sites were statistically significant. B-SB proved to be a suitable grafting material with simultaneously placed implants in sinus floor augmentation procedures.

Adult↗

Characterization of bone around titanium implants and bioactive glass particles: an experimental study in rats.

PURPOSE: Many situations in clinical practice require metallic implants to be combined with bone grafts and/or bone substitutes such as bioactive glass (BG). Upon implantation, silica-based BG particles are transformed into a shell containing calcium and phosphate that loses its inner silicon-rich core. The release of silicon by BG particles and its incorporation by newly formed bone tissue in the peri-implant area had not been studied to date. MATERIALS AND METHODS: Thirty Wistar rats were used throughout. Under anesthesia, a commercially pure titanium (Ti) laminar implant was placed inside the medullary compartment of the tibia (Ti group), while in the contralateral tibia (Ti/BG group) a titanium laminar implant and melt-derived BG 45S5 particles were implanted. The animals were sacrificed 14, 30, and 60 days postimplantation. The tibiae were resected, radiographed, and embedded in methyl methacrylate resin. Sections were stained with toluidine blue and analyzed by light microscopy and energy-dispersive x-ray analysis (EDX). The presence of silicon, calcium, and phosphorus was evaluated in the BG particles and in the peri-implant bone tissue for each of the experimental times. RESULTS: The histomorphometric study revealed an increase in peri-implant bone thickness in the Ti/BG group as compared to the Ti group. EDX of newly formed bone tissue showed a transient appearance of silicon at 14 and 30 days postimplantation and a rise in the calcium:phosphorus ratio in peri-implant bone tissue in the Ti/BG group. DISCUSSION: The present study shows an increase in reactive medullary bone formation when BG particles are implanted around a Ti implant. CONCLUSION: The results described in the present study reveal that the release of Si by BG particles is an important issue that warrants further study.

Animals↗

Treatment of distal radial fractures with grafting and K-wiring.

We present a series of 10 distal radius fractures treated with either bone substitute or xenograft, and Kapandji's technique (intra-focal threaded Kirschner wires which lever on the graft before penetrating the opposite diaphyseal cortex). The Kirschner wires are buried. Long-term follow-up (one to five years, mean 2.8 years) shows very little secondary displacement (up to 3 mm loss of radial height on the antero-posterior views and none on the sagittal views), excellent tolerability and integration of substitute and good function. The above operative technique has the advantage to allow immediate mobilisation of the wrist.

Aged↗

Interporous hydroxyapatite as a bone graft substitute in tibial plateau fractures.

The metaphyseal defects in 40 patients with displaced tibial plateau fractures necessitating surgical repair were filled with either cancellous autograft or interporous hydroxyapatite. Roentgenographic and clinical assessments at follow-up periods averaging 15.4 months (autograft) and 34.5 months (hydroxyapatite) demonstrated no significant differences in the two groups. Interporous hydroxyapatite is a safe, effective alternative to autogenous cancellous bone for the filling of metaphyseal defects associated with tibial plateau fractures.

Adolescent↗

Sinus elevation. Caldwell Luc approach--has it gone passed its use-by date?

The introduction of the osteotome technique in sinus elevation has diminished the usage of the Caldwell Luc approach. With the successful result obtained by adding platelet rich plasma to bone and/or bone substitute and the possible future use of rhBMP-2, the Caldwell Luc approach cannot be discarded. A review of the literature is presented.

Alveolar Ridge Augmentation↗

Resorbable bioceramics based on stabilized calcium phosphates. Part II: evaluation of biological response.

Synthetic materials capable of being remodelled in vivo by the same processes responsible for natural bone turnover have long been sought for use as an artificial bone substitute. These materials must ideally combine osteoinductive capacity with the ability to withstand random dissolution at normal physiological pH, while being resorbed by natural cell-mediated processes. Resorbable calcium phosphate based coatings and bulk ceramics have been developed which promote the uniform deposition of new mineralized bone matrix thus enabling rapid integration with the surrounding host bone tissue in vivo. Furthermore, a critical result of this study is the determination that the silicon-stabilized calcium phosphate ceramics are essentially insoluble in biological media but are resorbed when acted upon by osteoclasts. In vitro biological testing and preliminary in vivo testing show that the important features of this new biomaterial are a characteristic calcium phosphate phase composition and a unique microporous morphology.

Absorbable Implants↗