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

Radiographic and histometric evaluation of a new form of bone-graft substitute derived from reef-building sea coral was performed in a canine metaphyseal defect model. Blocks of this material were implanted into the proximal tibial metaphyses of eight dogs, with radiographic densitometry and harvesting performed at two, four, six, and 12 months. Histometric analysis demonstrated progressive apposition of host compact bone at the margins and trabecular bone at the interior of the implants with time following surgery. Corrected transmission density determinations correlated significantly with degree of osseous ingrowth (R = -0.78), void volume fraction (R = 0.88), and postoperative interval (R = 0.88). These results support the successful early application of coralline hydroxyapatite bone-graft substitutes as an alternative to autogenous grafting in the clinical setting, and indicate that the course of incorporation into host bone can be noninvasively monitored using densitometric techniques.

Absorptiometry, Photon↗

Release of gentamicin from bone regenerative materials: an in vitro study.

Antibiotic loading of bone regenerative materials is a promising way to protect augmentation procedures from infection during the resorption phase of bone substitutes. Especially in the early stage of implantation, it should protect the grafted site against microbiological pathogens. The present study reports the release kinetics of gentamicin after loading from two synthetic bone filling materials. The first, BONITmatrix, is a biphasic calcium phosphate silica composite obtained by the sol-gel route consisting of 13% silicon dioxide (w/w) and calcium phosphates (hydroxyapatite/beta-tricalcium phosphate 60/40 w/w). The second, Synthacer, is a sintered hydroxyapatite ceramic. Gentamicin was loaded by dipping and by vacuum coating. Release kinetics of the loaded Gentamicin was investigated by fluorescence polarization immunoassay and by staphylococcus aureus assay. By dipping, loading failed for Synthacer, and it was 12.7 mg gentamicin per gram bone substitute for BONITmatrix. By vacuum coating, loading was 11.3 mg gentamicin per gram bone substitute for Synthacer and 7.4 mg gentamicin per gram bone substitute for BONITmatrix. Distinct release kinetics were measured. For Synthacer, a high initial release was followed by a lower protracted release level up to 28 days. For BONITmatrix release was continuous over the investigated 70-day period. The present data suggest that the porosity properties at the nano- and microscopic levels, or the composition are responsible for antibiotic loading and subsequent release.

Anti-Bacterial Agents↗

Osteoinductive bone graft substitutes for spinal fusion: a basic science summary.

An understanding of precise biologic mechanisms at work during spinal fusion healing is just beginning to evolve. Current molecular biology research has shown this process to be multifactorial and extremely complex. With the advent of improved animal models to study the biology of spinal fusion, essential information regarding the basic science behind arthrodesis has advanced knowledge of this process. Moreover, with advances in local gene therapy as well as osteoinductive proteins and osteoinductive carrier matrices, the orthopedic surgeon will soon enter into a new era of biologic manipulation for fusion.

Animals↗

Effectiveness of local antibiotic delivery with an osteoinductive and osteoconductive bone-graft substitute.

BACKGROUND: The morbidity associated with open fractures and open fracture treatment is well established. An osteoinductive and osteoconductive bone-graft substitute that prevents infection would decrease the number of procedures required to treat contaminated fractures by eliminating the need for surgical removal of cement beads and perhaps autograft harvest. We hypothesized that the combination of tobramycin-impregnated calcium sulfate pellets and demineralized bone matrix would prevent the establishment of infection in a contaminated fracture model. METHODS: A unicortical 12-mm-diameter defect was created in the proximal tibial metaphysis of twenty-nine Spanish goats. After contaminating the wounds with an infective dose of Staphylococcus aureus, we divided the animals into four groups. The negative control group received no treatment, the positive control group received tobramycin-impregnated polymethylmethacrylate beads, the demineralized bone matrix group received 2.5 mL of demineralized bone matrix, and the experimental group received tobramycin-impregnated calcium sulfate pellets with 2.5 mL of demineralized bone matrix. Radiographs were made and intraosseous tissue cultures were performed on postoperative day 21. RESULTS: The cultures showed no evidence of intramedullary infection in the experimental or the positive control group, but they were positive for Staphylococcus aureus in six of the seven goats in the negative control group and seven of the eight goats in the demineralized bone matrix group. CONCLUSIONS: The combination of tobramycin-impregnated calcium sulfate pellets and demineralized bone matrix was effective in preventing intramedullary Staphylococcus aureus infection in a contaminated goat fracture model.

Animals↗

Healing pattern of bone defects covered by different membrane types--a histologic study in the porcine mandible.

Few investigations on guided bone regeneration (GBR) focus on the behaviour of tissues adjacent to barrier membranes. This study was conducted to (1) evaluate the barrier function potential of different resorbable and nonresorbable membranes for GBR, (2) investigate their structural changes after different intervals, and (3) characterize tissue composition and reaction adjacent to the barrier by qualitative histologic evaluation. Seven barriers for GBR were used per animal (made of dense or expanded polytetrafluoroethylene (d/ePTFE), titanium, polyetherurethane, collagen and two polylactide-polyglycolide-/-trimethylenecarbonate-co-polymers (PLPG, LPGTC) in standardized defects not exceeding the critical size) without using bone substitution material or autogenous bone at the right inferior margin of the mandibles of six domestic pigs. Samples of the defect areas with membranes were harvested after 2 days (one animal), 4 and 8 (two animals, each) and 12 weeks (one animal), respectively. The healing of bone defects was completed in all animals after 12 weeks. Nonresorbable barriers prevented the soft tissue in-growth into standardized defects. Thinner layers of fibrous tissue were seen underneath the dense and rigid barriers (dPTFE, titanium) when compared with collagen and PLPG/LPGTC, in which soft-tissue plugs occupied the crestal defect portion. PLPG-/LPGTC-barriers underwent structural changes after 4 weeks and revealed blistered central layers, whereas structural changes were not evident in nonresorbable barriers. The degradation of PLPG-/LPGTC-membranes was present with in-growth of fibres, vessels, and cells. Using collagen or synthetic polymer barriers for GBR, the application of bone or bone substitutes to prevent membrane prolapse into the defect is suggested.

Animals↗

Use of bone graft substitutes and bioactive materials in treatment of distal radius fractures.

Although autogenous bone graft has been shown to be useful in the treatment of distal radius fractures, the role of bone graft substitutes and the optimal replacement material remains unclear. Several products are commercially available, each with differing osteoconductive, osteoinductive, and structural properties. Indications and choice of graft substitute should be based on the needs of the individual case with regard to need for structural support, gap filling, or bone healing stimulation. Further comparative research will help clarify the indications and most appropriate material for a given fracture and clinical situation.

Biocompatible Materials↗

Coralline hydroxyapatite bone graft substitutes in a canine metaphyseal defect model: radiographic-biomechanical correlation.

Radiographic and biomechanical assessment of a new type of bone graft substitute derived from reef-building sea coral was performed in a canine metaphyseal defect model. Blocks of this material and autogenous iliac crest graft were implanted, respectively, into the right and left proximal tibial metaphyses of eight dogs. Qualitative and quantitative radiographic evaluation was performed in the immediate postoperative period and at 6 months after surgery. Biomechanical testing was carried out on all grafts following harvest at 6 months, as well as on nonimplanted coralline hydroxyapatite and autogenous iliac cancellous bone. In contrast to autografts, incorporation of coralline implants was characterized by predictable osseous growth and apposition with preservation of intrinsic architecture. Greater percent increase in radiographic density, higher ultimate compressive strength, and lower stiffness with incorporation were documented advantages of coralline hydroxyapatite over autogenous graft. Densitometric measurements correlated moderately with strength for both types of graft material (r = -0.65). These promising results have important implications to the clinical application of coralline hydroxyapatite bone graft substitutes as an alternative to autogenous grafting.

Absorptiometry, Photon↗

The use of coral as a bone graft substitute.

Experiments have been performed to investigate the use of coral skeletons as bone graft substitutes. Skeletal fragments of different coral genera were implanted into cortical and spongy bone defects and used to bridge transcortical resections in the femur. The implant site was monitored for up to 18 months. Radiographically, both cortical and spongy bone defects were at least partially filled by new bone after 8 weeks while the implants underwent continuous resorption. Coral resorption and replacement by new tissue was also observed in the transcortical resections. The process of resorption was attributed to the enzymatic attack, especially carboanhydrase. This was confirmed by experiments in which dogs were implanted with coral in transcortical resections and treated daily with acetazolamide, a carboanhydrase inhibitor; the absorption appeared delayed and the resections failed to heal.

Acetazolamide↗

Lack of beneficial effects of platelet-rich plasma on sinus augmentation using a fluorohydroxyapatite or autogenous bone: an explorative study.

BACKGROUND: Maxillary sinus augmentation is frequently necessary before placement of dental implants in the posterior maxilla. Besides autogenous bone graft, various bone substitutes have been used, with favourable results. Although platelet-rich plasma (PRP) has been used in the field of oral and maxillofacial surgery for years, its beneficial effects on osseous regeneration still remain unclear. The aim of this study was to evaluate the short and long time effects of PRP on single-stage sinus augmentation using autogenous bone or a fluorohydroxyapatite (Algipore) in a randomized prospective animal study. METHODS: After extraction of maxillary premolars of sixteen minipigs, the wounds were allowed to heal for 2 months. Then, sinus augmentations were performed bilaterally using one of the following grafting materials: autogenous bone and Algipore with or without PRP. Three dental implants (Ankylos) were installed in each sinus simultaneously. Four animals were euthanized at each period of observation (1, 2, 8 and 12 months). Implant-bearing specimens were sectioned bucco-lingually along the long axis of implants and undecalcified ground specimens were prepared. The bone-implant-contact (BIC) was measured by means of microradiographic examination. For histological evaluation, the specimens were stained with toluidin blue, and the percentage of the newly formed bone and the remaining bone substitute were evaluated. RESULTS: The grafting materials chosen showed increasing levels of BIC and newly formed bone throughout the period of observation in both PRP and non-PRP groups. Adding PRP resulted in lower BIC and newly formed bone compared with autogenous bone grafts or Algipore alone. However, a statistical significance was not found. The percentages of the remaining bone substitute in both the PRP and non-PRP groups were closely comparable in all observation periods. CONCLUSIONS: The application of PRP could not reveal significant beneficial effects on the BIC, the percentage of the newly formed bone and the remaining bone substitute in this study.

Animals↗

Coralline hydroxyapatite bone graft substitutes: radiographic evaluation.

The authors discuss a recently described bone graft material substitute derived from sea corals. They briefly review its background leading to the potential for clinical use. Radiologic evaluation is provided, with attention directed to its characteristics, compared with other bone grafts.

Biocompatible Materials↗

Defect repair in the rat mandible with bone morphogenic proteins and marrow cells.

OBJECTIVE: To investigate the ability of a bone growth factor mixture and bone marrow cells to repair a critical size defect of the rat mandibular body. DESIGN: Prospective, randomized controlled trial. SUBJECTS: Thirty-seven male Fischer rats. INTERVENTIONS: Critical size defects 4 mm in diameter were created in the left mandibular bodies of the rats. The defects were filled with a bone marrow cell suspension (group 1), a synthetic bone matrix consisting of bovine collagen and calcium hydroxyapatite cement (group 2), the matrix and marrow cells (group 3), the matrix with 100 micro g of bone growth factor mixture (group 4), or the matrix with bone growth factor mixture and marrow cells (group 5). Animals were killed after 8 weeks, and the nondemineralized specimens were processed histologically. Specimens from group 1 were not processed because there was no grossly appreciable bone regeneration. Stereologic techniques were used to determine and compare the volume fractions and volume estimates of mature bone, new bone, osteoid, marrow, remaining cement, and fibrous tissue in each defect. RESULTS: Volumes of mature bone, new bone, and remaining cement did not differ significantly among the groups (P =.30 for mature bone, P =.17 for new bone, and P =.34 for cement). However, group 4 and 5 specimens contained significantly more osteoid and larger marrow spaces than did the group 2 and 3 specimens (P<.001 for both). The specimens in groups 2 and 3 contained significantly more fibrous tissue ingrowth than did those in groups 4 and 5 (P<.001). CONCLUSION: The synthetic bone substitute containing bone growth factor mixture was effective in stimulating new bone and osteoid development in the rat mandibular model.

Animals↗

Regeneration of bone in the presence of calcium sulfate.

I describe 110 patients in whom diseased and destructed bone was restored to normal healthy bone. The first ten patients were healed by using bismuth-iodoform, and the following 100 patients were treated using the hemihydrate of calcium sulfate (CaSO4.2H3O). Both alloplasts were replaced in all patients by normal healthy cancellous bone within two to four months. It is a safe procedure in which bone regeneration is stimulated to a maximum rate. During June 1974, bismuth-iodoform was used as an allograft. On July 9, 1974, the first three operations in the history of otorhinolaryngology, to my knowledge, were performed using CaSO4. Normal physiologic absorption of CaSO4 occurs with the simultaneous deposition of autogenous cancellous bone. Calcium sulfate is an outstanding bone substitute, ensuring bone formation and giving results comparable with autogenous bone, if not better.

Adolescent↗

Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier.

Bone substitute materials can induce bone formation in combination with mesenchymal stem cells (MSC). The aim of the current study was to examine ectopic in vivo bone formation with and without MSC on a new resorbable ceramic, called calcium deficient hydroxyapatite (CDHA). Ceramic blocks characterized by a large surface (48 m2/g) were compared with beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HA) ceramics (both ca. 0.5 m2/g surface) and demineralized bone matrix (DBM). Before implantation in the back of SCID mice carriers were freshly loaded with 2x10(5) expanded human MSC or loaded with cells and kept under osteogenic conditions for two weeks in vitro. Culture conditions were kept free of xenogenic supplements. Deposits of osteoid at the margins of ceramic pores occurred independent of osteogenic pre-induction, contained human cells, and appeared in 416 MSC/CDHA composites compared to 216 MSC/beta-TCP composites. ALP activity was significantly higher in samples with MSC versus empty controls (p<0.001). Furthermore, ALP was significantly (p<0.05) higher for all ceramics when compared to the DBM matrix. Compared to previous studies, overall bone formation appeared to be reduced possibly due to the strict human protocol. Ectopic bone formation in the novel biomaterial CDHA varied considerably with the cell pool and was at least equal to beta-TCP blocks.

Aged↗

Quantitative histological analysis of bony ingrowth within the biomaterial Polyactive implanted in different bone locations: an experimental study in rabbits.

The quantity of bone formed in cylinders of a newly developed erodible copolymer, Polyactive (PA60/40) was examined. PA60/40 was implanted in three different bone locations in the rabbit: in the cortex, in bone marrow and in trabecular subchondral bone. Bony ingrowth was assessed after 4, 8, 26 and 52 w after the operation and investigated by histology and image analysis. The ingrowth of bone was observed in PA60/40 placed in the cortex from 4 w onwards. After 8 w, more than 90% of the pores of the biomaterial were filled with dense bone. In bone marrow, initially some bone formation was seen. After 26 w, all newly formed bone was resorbed. Subchondral bone formation was less than in the cortex of the femur, but somewhat comparable to the amount of bone found in healthy trabecular bone. Bone formation appeared not to be affected by the degradation of the biomaterial. It was concluded that Polyactive is a suitable bone graft substitute. Bone formation within PA60/40 is site-dependent and this follows Wolff 's law.

Journal Article↗

The effects of bovine trabecular bone matrix particulates on cortical bone repair.

This paper reports the effects of a synthetic bone substitute and bone allograft on cortical bone repair in an experimental model. To test the hypothesis that bovine trabecular bone matrix, BBM, can enhance the repair rate of cortical bone, osteotomies were created in the rabbit fibula and filled with either allograft or BBM particulates or left empty as controls. At five weeks post-surgery, mechanical tests and histological evaluations were performed. No significant differences were observed in the mechanical properties of the healing bone in the three animal groups (n=6). Histologically, the medullary cavity was obstructed and the cross-sectional area ratio of the osteotomies to intact bone was approximately 3 : 1. Highly significant area differences were observed between the intact bone group and both the BBM and the allograft groups (p< 0.001). At the junction between the original bone and the newly formed bone, both woven and lamellar bone microstructures were prevalent. However, in the BBM filled defects, the woven bone microstructure was not ostentatious. It is concluded that failure to demonstrate significantly differences between the treatments were due to the small sample sizes and or the efficacy of the tensile analysis.

Journal Article↗

Factors influencing the compressive strength of an injectable calcium sulfate-hydroxyapatite cement.

A biphasic injectable bone substitute, suitable for filling bone defects, that sets in the body, based on calcium sulfate and hydroxyapatite (HA), is presented. For applications in bone defects the compressive strength is important to assure support of the defect site during loading when the patient is weight bearing. To control the strength, the influence of four different factors; the liquid-to-powder (L/P) ratio, the HA particle morphology, the HA content and the amount of accelerator, were investigated. alpha-Calcium sulfate hemihydrate (CSH) and four different HA powders (three sintered and one spray-dried) were used. All differed in size and morphology. CSH and each HA powder were mixed together with distilled water to form the bone substitute. An accelerator, in form of calcium sulfate dihydrate, was added to the powder phase to obtain an adequate setting time. Cylindrical specimens were compression tested. A lower L/P-ratio gave stronger cement, but was more difficult to inject. The shape and the morphology of the HA particles influenced the strength, and reducing the amount of HA increased the strength. The amount of accelerator (calcium sulfate dihydrate) had no influence.

Journal Article↗

Injectable bioactive glass/biodegradable polymer composite for bone and cartilage reconstruction: concept and experimental outcome with thermoplastic composites of poly(epsilon-caprolactone-co-D,L-lactide) and bioactive glass S53P4.

Injectable composites (Glepron) of particulate bioactive glass S53P4 (BAG) and Poly(epsilon-caprolactone-co-D,L-lactide) as thermoplastic carrier matrix were investigated as bone fillers in cancellous and cartilagineous subchondral bone defects in rabbits. Composites were injected as viscous liquid or mouldable paste. The glass granules of the composites resulted in good osteoconductivity and bone bonding that occurred initially at the interface between the glass and the host bone. The bone bioactivity index (BBI) indicating bone contacts between BAG and bone, as well as the bone coverage index (BCI) indicating bone ongrowth, correlated with the amount of glass in the composites. The indices were highest with 70 wt % of BAG, granule size 90-315 microm and did not improve by the addition of sucrose as in situ porosity creating agent in the composite or by using smaller (<45 microm) glass granules. The percentage of new bone ingrowth into the composite with 70 wt % of BAG was 6-8% at 23 weeks. At the articular surface cartilage regeneration with chondroblasts and mature chondrocytes was often evident. The composites were osteoconductive and easy to handle with short setting time. They were biocompatible with low foreign body cellular reaction. Results indicate a suitable working concept as a filler bone substitute for subchondral cancellous bone defects.

Animals↗