Interconnected Porous Calcium Hydroxyapatite Research Articles

On-lay grafting of a calcium hydroxyapatite bone substitute: A preliminary animal experimental study

BackgroundBone substitutes are widely accepted for various clinical applications. However, the usage is predominantly intraosseous implantation, whereas extraosseous on-lay grafting is rare and lacks scientific evidence. The purpose of this study is to elucidate whether osteoconduction occurs in on-lay grafted bone substitute. MethodsCustom-made interconnected porous calcium hydroxyapatite ceramic (IPCHA) was on-lay grafted with screw or anchor fixation (S- and A-groups, respectively) at the anterior aspect of the femur of skeletally mature Japanese white rabbits. At 3, 6 and 12 weeks postoperatively, 4 samples for each time point and each group were evaluated by microfocus computed tomography (micro-CT) and histology. ResultsVolume-rendered three-dimensional micro-CT images showed a high-density calcified area infiltrating IPCHA from the femoral cortex as of 6 weeks. When quantified, the calcified volume per unit volume first showed no difference between the two groups at 3 weeks but increased over time, and became significantly greater in the S-group than in the A-group (p = 0.012 and 0.004 at 6 and 12 weeks, respectively). Histologically, IPCHA pores were first occupied by fibrous tissue at 3 weeks; then, the pores adjacent to the femoral cortex were gradually replaced by bony tissue as of 6 weeks for both fixations. ConclusionsIPCHA allowed new bone formation inside the material even though it was implanted in an on-lay fashion on the cortical bone. Our results suggested that on-lay grafted IPCHA exerted its osteoconductivity well, with more new bone forming in screw-fixated samples than in anchor-fixated samples.

Impact of non-thermal plasma surface modification on porous calcium hydroxyapatite ceramics for bone regeneration.

In the physiochemical sciences, plasma is used to describe an ionized gas. Previous studies have implicated plasma surface treatment in the enhancement of hydrophilicity of implanted musculoskeletal reconstructive materials. Hydroxyapatite (HA) ceramics, widely used in bone tissue regeneration, have made great advancements to skeletal surgery. In the present study, we investigate the impact of low-pressure plasma on the interconnected porous calcium hydroxyapatite (IP-CHA) both in vitro and in vivo. Our results indicate that dielectric barrier discharge (DBD) plasma, when used with oxygen, can augment the hydrophilicity of non-porous HA surfaces and the osteoconductivity of the IP-CHA disc via increased water penetration of inner porous structures, as demonstrated through microfocus computed tomography (μCT) assay. In vivo implantation of plasma-treated IP-CHA displayed superior bone ingrowth than untreated IP-CHA. Though plasma-treated IP-CHA did not alter osteoblast cell proliferation, it accelerated osteogenic differentiation of seeded marrow mesenchymal stem cells. In vitro X-ray photoelectron spectroscopy (XPS) revealed that this plasma treatment increases levels of oxygen, rather than nitrogen, on the plasma-treated IP-CHA surface. These findings suggest that plasma treatment, an easy and simple processing, can significantly improve the osteoconductive potential of commonly used artificial bones such as IP-CHA. Further optimization of plasma treatment and longer-term follow-up of in vivo application are required toward its clinical application.

Osseointegration aspects of placed implant in bone reconstruction with newly developed block-type interconnected porous calcium hydroxyapatite

ABSTRACTArtificial bone has been employed to reconstruct bone defects. However, only few reports on implant placement after block bone grafting exist. Objectives The purpose of this study was to evaluate the osseointegration of dental implant in bone reconstructions with interconnected porous calcium hydroxyapatite (IP-CHA).Material and Methods The IP-CHA cylinders (D; 4.3 mm, H; 10.0 mm) were placed into bone sockets in each side of the femurs of four male dogs. The IP-CHA on the right side was a 24-week sample. Twelve weeks after placement, a titanium implant was placed into a socket that was prepared in half of the placed IP-CHA cylinder on the right side. On the left side, another IP-CHA cylinder was placed as a 12-week sample. After another 12 weeks, the samples were harvested, and the bone regeneration and bone-implant contact (BIC) ratios were measured.Results New bone formation area was superior in the 24-week IP-CHA compared with the 12-week IP-CHA. BIC was not significantly different between IP-CHA and the parent sites. Osseointegration was detected around the implant in IP-CHA-reconstructed bone.Conclusion Our preliminary results suggest that IP-CHA may be a suitable bone graft material for reconstructing bones that require implant placement.

Inorganic polyphosphate adsorbed onto hydroxyapatite for guided bone regeneration: An animal study

Inorganic polyphosphate (poly(P)) is recognized as a therapeutic agent that promotes fibroblast growth factor and enhances osteogenic differentiation, and in vivo, when adsorbed onto interconnected porous calcium hydroxyapatite (IP-CHA) enhances bone regeneration. The present study focused on the effect of poly(P) adsorbed onto IP-CHA granules (Poly(P)/IP-CHA) in guided bone regeneration (GBR). Dental implants were placed into the edentulous mandibular areas of five Beagle-Labrador hybrid dogs with screw expose on the buccal side, and then bone defects were filled Poly(P)/IP-CHA (test) or IP-CHA (control). After 12 weeks, histological evaluation and histomorphometrical analysis were performed. Newly-bone formation around exposed implant screw was clearly detected in the test-group. The ratio for regenerated bone height in the test group versus the control-group was 85.6±20.2 and 62.6±23.8, respectively, with no significant difference, while, that for bone implant contact was significantly higher (67.9±11.8 and 48.8±14.1, respectively). These findings indicate that Poly(P)/IP-CHA enhances bone regeneration in GBR.

Use of the granulated interconnected porous calcium hydroxyapatite ceramics for instrumented spinal posterior fusion; Six cases report

Use of the granulated interconnected porous calcium hydroxyapatite ceramics for instrumented spinal posterior fusion; Six cases report

Development of Implant/Interconnected Porous Hydroxyapatite Complex as New Concept Graft Material

BackgroundDental implant has been successfully used to replace missing teeth. However, in some clinical situations, implant placement may be difficult because of a large bone defect. We designed novel complex biomaterial to simultaneously restore bone and place implant. This complex was incorporated implant into interconnected porous calcium hydroxyapatite (IP-CHA). We then tested this Implant/IP-CHA complex and evaluated its effect on subsequent bone regeneration and implant stability in vivo.Methodology/Principal FindingsA cylinder-type IP-CHA was used in this study. After forming inside of the cylinder, an implant was placed inside to fabricate the Implant/IP-CHA complex. This complex was then placed into the prepared bone socket in the femur of four beagle-Labrador hybrid dogs. As a control, implants were placed directly into the femur without any bone substrate. Bone sockets were allowed to heal for 2, 3 and 6 months and implant stability quotients (ISQ) were measured. Finally, tissue blocks containing the Implant/IP-CHA complexes were harvested. Specimens were processed for histology and stained with toluidine blue and bone implant contact (BIC) was measured. The ISQs of complex groups was 77.8±2.9 in the 6-month, 72.0±5.7 in the 3-month and 47.4±11.0 in the 2-month. There was no significant difference between the 3- or 6-month complex groups and implant control groups. In the 2-month group, connective tissue, including capillary angiogenesis, was predominant around the implants, although newly formed bone could also be observed. While, in the 3 and 6-month groups, newly formed bone could be seen in contact to most of the implant surface. The BICs of complex groups was 2.18±3.77 in the 2-month, 44.03±29.58 in the 3-month, and 51.23±8.25 in the 6-month. Significant difference was detected between the 2 and 6-month.Conclusions/SignificanceWithin the results of this study, the IP-CHA/implant complex might be able to achieve both bone reconstruction and implant stability.

Efficient modification of the surface properties of interconnected porous hydroxyapatite by low-pressure low-frequency plasma treatment to promote its biological performance

Dielectric barrier discharge plasma treatment at low pressure is found to significantly improve the biological performance of artificial bones made of interconnected porous calcium hydroxyapatite (IP-CHA). One of the essential parameters associated with their biological performance is hydrophilicity of their exterior surfaces as well as surfaces of inner pores. It is found that plasma treatment at low pressures is highly effective in making the inner pore surfaces more hydrophilic. Preliminary in vivo experiments of plasma-treated IP-CHA artificial bones in rats have shown fast formation of blood vessels in their inner pores, implying the increase in osteoconductivity due to the plasma treatment.

Usefulness of the interconnected porous calcium hydroxyapatite ceramic spacers in double-door laminoplasty of the cervical spine

Usefulness of the interconnected porous calcium hydroxyapatite ceramic spacers in double-door laminoplasty of the cervical spine

Prefabrication of vascularized bone graft using an interconnected porous calcium hydroxyapatite ceramic in presence of vascular endothelial growth factor and bone marrow mesenchymal stem cells: Experimental study in rats

Objectives:The purpose of this experimental pilot study was to create a prefabricated vascularized bone graft using interconnected porous calcium hydroxyapatite ceramic (PCHC) block by combining vascular bundle implantation, rat bone marrow mesenchymal stem cells and administration of vascular endothelial growth factor (VEGF) in a rat model.Materials and Methods:Sixty male Sprague-Dawley rats were used. Experimental animals were divided into six groups, each of which comprised 10 rats. The PCHC blocks were implanted in the medial thigh region in groups I, III, and V without vascular bundle implantation. The PCHC blocks were vascularized by the superficial inferior epigastric artery and vein in groups II, IV and VI. These vessels were passed through the hole of the PCHC blocks. Mesenchymal stem cells were administered into the PCHC in groups III, IV, V and VI. In addition, both mesenchymal stem cells and VEGF were administered in group V and VI. The presence and density of any new bone formation and neovascularization from the vascular bundle was evaluated by X-ray, microangiography, scintigraphy, biochemical analysis and histomorphometry.Results:The newly formed vessels and bone formations were significantly greater in group VI, in which both mesenchymal stem cells and VEGF were applied.Conclusion:This preliminary study suggests that: Both mesenchymal stem cells and VEGF provide vascularized bone prefabrication by enhancing neovascularization and osteogenesis in a shorter time compared to only VEGF application.

Improvement of Hydrophilicity of Interconnected Porous Hydroxyapatite by Dielectric Barrier Discharge Plasma Treatment

Dielectric barrier discharge plasma treatment has been found to significantly improve hydrophilicity of the surfaces of interconnected porous calcium hydroxyapatite (IP-CHA), particularly that of wall surfaces of the internal pores. IP-CHA has been clinically used as a material for bone substitutes in bone tissue regeneration. Higher hydrophilicity of IP-CHA obtained in this method is expected to further increase the osteoconductivity of IP-CHA.

Comparative evaluation of bone regeneration using spherical and irregularly shaped granules of interconnected porous hydroxylapatite. A beagle dog study

Bone regeneration stimulated by two different shapes of interconnected porous calcium hydroxyapatite (IP-CHA) granules was evaluated in the mandibles of 3 beagle dogs. Deferent shapes of IP-CHA were used, spherical (spherical shaped IP-CHA granules) and irregular shapes (irregularly shaped IP-CHA granules). Two bone sockets (3mm in diameter and 5mm in depth) were prepared in the right edentulous mandible of each animal where right premolars had been extracted and sites healed for 3 months. The two types of IP-CHA were filled into the sockets to stimulate bone regeneration. New bone formation was evaluated histologically at 4, 8 and 12 weeks after filling. At 4 weeks, little bone formation was apparent in any of the bony sockets. At 8 weeks, newly formed bone was detected between the granules but not in the pores. In contrast, at 12 weeks, bone formation was clearly observed not only between the granules but also inside the granule pores. Comparing the two sites at 8 and 12 weeks, more bone formation was detected in sites receiving irregularly shaped IP-CHA than in sites receiving spherical IP-CHA. These results indicate that use of irregularly shaped IP-CHA may enhance bone regeneration. The results of this preliminary study suggest that irregularly shaped IP-CHA granules may have more possible usefulness than spherically shaped granules as a scaffold for bone regeneration.

Enhancement of bone formation in an experimental bony defect using ferumoxide-labelled mesenchymal stromal cells and a magnetic targeting system

We used interconnected porous calcium hydroxyapatite ceramic to bridge a rabbit ulnar defect. Two weeks after inducing the defect we percutaneously injected rabbit bone marrow-derived mesenchymal stromal cells labelled with ferumoxide. The contribution of an external magnetic targeting system to attract these cells into the ceramic and their effect on subsequent bone formation were evaluated. This technique significantly facilitated the infiltration of ferumoxide-labelled cells into ceramic and significantly contributed to the enhancement of bone formation even in the chronic phase. As such, it is potentially of clinical use to treat fractures, bone defects, delayed union and nonunion.

Interconnected Porous Calcium Hydroxyapatite Demonstrated Comparable Bone Bonding to Autogeous Bone for Cervical Laminoplasty Spacers

Cervical laminoplasty is designed to preserve the posterior structures, so as to prevent postoperative development of instability and cervical kyphosis. The technique requires successful reconstruction of the laminae of vertebral arches, as sinking or non-union of the expanded laminae may induce neurological regression, segmental motor paralysis, and postoperative axial pain. A novel interconnected porous calcium hydroxyapatite (IP-CHA) with sufficient biocompatibility and mechanical strength was developed as an artificial bone substitute.

Bone-marrow-derived mononuclear cells with a porous hydroxyapatite scaffold for the treatment of osteonecrosis of the femoral head

We have investigated the effectiveness of the transplantation of bone-marrow-derived mononuclear cells (BMMNCs) with interconnected porous calcium hydroxyapatite (IP-CHA) on early bone repair for osteonecrosis of the femoral head. We studied 22 patients (30 hips) who had osteonecrosis with a minimum follow-up of one year after implantation of BMMNCs. The mean age at surgery was 41 years (18 to 64) and the mean period of follow-up was 29 months (19 to 48). In a control group, cell-free IP-CHA was implanted into a further eight patients (9 hips) with osteonecrosis of the femoral head and the outcomes were compared. A reduction in the size of the osteonecrotic lesion was observed subsequent to hypertrophy of the bone in the transition zone in the BMMNC group. In three patients in the treatment group progression to extensive collapse was detected. In the control group subtle bone hypertrophy was observed, but severe collapse of the femoral head occurred in six of eight hips. In this limited study the implantation of BMMNCs and IP-CHA appears to confer benefit in the repair of osteonecrosis and in the prevention of collapse.

Enhanced initial bone regeneration with inorganic polyphosphate-adsorbed hydroxyapatite

Inorganic polyphosphate (poly(P)) can promote binding between fibroblast growth factors and their receptors and enhance osteoblastic cell differentiation and calcification. This study evaluated the possibilities for poly(P) adsorbed onto interconnected porous calcium hydroxyapatite (IP-CHA) as a new bone regeneration material. Prepared 1%, 5%, 25% and 50% poly(P)/IP-CHA composites showed the elution peak of poly(P) between 15 and 20 min, respectively, with the highest value from 50% poly(P)/IP-CHA in vitro. Histologically, at 1 week of placement into the femur of rabbits, granulation tissue had penetrated into the pores in all composites and IP-CHA as a control. In contrast, at 2 weeks of placement, newly formed lamellar bone was found in all groups, although a higher amount of bone regeneration was obviously formed in the 25% and 50% poly(P)/IP-CHA with a significantly higher value of bone regeneration ratio of 50% poly(P)/IP-CHA. These results indicate that 25% and 50% poly(P)/IP-CHA composites may enhance initial bone regeneration.

Treatment of digital deformities in Ollier's disease patients with custom-made interconnected porous calcium hydroxyapatite ceramics (IP-CHA)—3 cases experience

Treatment of digital deformities in Ollier's disease patients with custom-made interconnected porous calcium hydroxyapatite ceramics (IP-CHA)—3 cases experience

Feasibility of prefabricated vascularized bone graft using the combination of FGF‐2 and vascular bundle implantation within hydroxyapatite for osteointegration

The aim of this study was to demonstrate the feasibility of the prefabricated vascularized bone graft using an interconnected porous calcium hydroxyapatite ceramic (IP-CHA) in combination with vascular bundle implantation and basic fibroblast growth factor (FGF-2) administration in rabbit model. Thirty Japanese white rabbits were used. To make a prefabricated bone graft, the saphenous artery and vein were passed through the hole of the IP-CHA. Hundred micrograms of FGF-2 was administered into the IP-CHA before implanting the vascular bundle. First and foremost, the IP-CHA was placed subcutaneously in the medial thigh of rabbits for 4 weeks. In the experimental group, a prefabricated vascularized bone graft was used while IP-CHA alone was used in the control group. Second, the prefabricated vascularized bone graft was transplanted from the subcutaneous implanted site into the medial femoral condyle defect of the same rabbit and IP-CHA alone was implanted as the control graft in a different animal. At 4 weeks posttransplantation, bone union with host bone could be observed in the experimental group. However, the area of bone formation of the control group was significantly higher than in the experimental at 2 and 4 weeks posttransplantation. We conclude that the prefabricated vascularized bone graft when transplanted into a bone defect showed the ability for bone union with the host bone, although further studies are needed to accelerate the process of bone formation.

Development of Cell-hybrid Artificial Bone: Effect of Osteogenic Differentiation of Bone Marrow Stromal Stem Cells on Bone Formation with Newly Developed Interconnected Porous Calcium Hydroxyapatite

The purpose of this study was to evaluate the effect of osteogenic differentiation of bone marrow stromal stem cells (BMSCs) on bone formation in a novel interconnected porous calcium hydroxyapatite (IP-CHA). BMSCs/IP-CHA composites, as a cell-hybrid artificial bone, were made by injecting BMSCs solution into IP-CHA scaffolds. To induce osteogenic differentiation, BMSCs/IP-CHA composites were subcultured for three, seven, 10, and 14 days. At the end of each subculture period, BMSCs/IP-CHA composites were examined by SEM and ALP staining. BMSCs/IP-CHA composites of different osteogenic groups of subculture were also placed into bone sockets in the right femur of beagle dogs. After four weeks, same placement procedure was done in the left femur. BMSCs/IP-CHA subcultured for 10 and 14 days were ALP-positive as opposed to those of three and seven days. At four weeks after placement, bone formation was superior at the 10- and 14-day subculture groups. Based on the results obtained, it was suggested that osteogenic differentiation periods with 10 and 14 days of subculture for BMSCs/IP-CHA as a cell-hybrid artificial bone were beneficial in promoting bone formation.

Augmentation of tendon attachment to porous ceramics by bone marrow stromal cells in a rabbit model

Tendon attachment to interconnected porous calcium hydroxyapatite ceramics (IP-CHA) with cultured bone marrow stromal cells (BMSC) was analysed. The purpose of this study was to evaluate whether BMSC in IP-CHA could augment the tendon attachment to IP-CHA histologically and biomechanically. Eighteen Japanese white rabbits were used. Cultured BMSCs were subcultured in IP-CHA. The grafted tendon and IP-CHA with BMSC complex were implanted in a bone defect of the knee [BMSC(+) group]. In the contralateral knee, a tendon and IP-CHA without BMSC complex were implanted [BMSC(-) group]. Histological findings of the interface between the tendon and IP-CHA were similar in the two groups 3 weeks after the operation. However, 6 weeks after the operation, more abundant bone formation around the tendon was observed in the BMSC(+) group. The direct apposition of the tendon to bone in pores and collagen fibre continuity between the tendon and fibrous tissue in pores were observed. In biomechanical evaluation, the maximum pull-out load of the tendon from the IP-CHA in the BMSC(+) group was significantly higher than that in the BMSC(-) group 6 weeks after the operation. BMSCs cultured in IP-CHA could augment tendon attachment to IP-CHA.

Effects of interconnecting porous structure of hydroxyapatite ceramics on interface between grafted tendon and ceramics

The purpose of this study was to evaluate histologically and biomechanically the interface between porous hydroxyapatite ceramics and a tendon grafted into ceramics, and to compare the interface in two ceramics with different porous structures: interconnected porous calcium hydroxyapatite ceramics (IP-CHA) with an effective porosity index (interpore diameter > 20 microm) of 63.6%, and porous calcium hydroxyapatite ceramics with less interconnection (HA-L) with an effective porosity index of 5.5%. The tendon-IP-CHA complex and the tendon-HA-L complex were implanted into the bone defects made in both knees of rabbits. With IP-CHA, abundant fibrous tissue, including vessels and collagen fiber continuity, was observed inside interface-region pores. The amount of osseous tissue in interface-region pores increased over time, and at 24 weeks after operation, the tendon was in direct contact with the osseous tissue in IP-CHA. With HA-L, the amount of fibrous tissue in interface-region pores was low and did not increase. The results of biomechanical analysis revealed that the maximum tendon pull-out load from IP-CHA was significantly higher than that from HA-L. With the porous hydroxyapatite ceramics having highly interconnecting porous structure, a bioactive interface was achieved between ceramics and grafted tendon. On the basis of these results, we conclude that bone defects, including tendon insertion, can be reconstructed using IP-CHA.