Composite Plaster/Hydroxylapatite Implants for Jaw Bone Restoration

Repair was compared in 4.4mm experimental rat mandibular ramus defects implanted with dense or porous HA particles with or without a plaster binder. Animals were sacrificed 6 months postimplantation. Specimens underwent gross, radiographic, histochemical and X-ray microanalytical examination. Gross and radiographic examinations showed good particle containment or retention only in defects filled with implants containing plaster. Only porous HA/plaster filled defects showed bone formation throughout the implant when examined histochemically by the PATS reaction and by X-ray microanalysis. They also showed greater radiographic opacity compared to dense HA/plaster implants. Only porous HA/plaster implants showed macroscopic bone formation. Examination of defects filled with porous HA/plaster or porous HA alone by the PATS reaction showed new cancellous bone around, and through the pores of, retained particles. The dense HA/plaster implants showed some new bone around the rims of the defects with only occasional bony incorporation of an HA particle. Dense particles in other areas showed only soft tissue encapsulation. Defects implanted with dense HA without plaster showed no new bone formation but retained particles were incorporated by fibrovascular tissue.

To evaluate the utility of subperiosteal tissue expansion (STE) for mandibular augmentation with hydroxylapatite (HA) particles, two experimental studies in adult mongrel dogs were performed. One was to observe histologic changes following STE and to compare the tissue response to STE with that to subcutaneous expansion. The other was to observe clinical and histologic changes following implantation of HA particles in the subperiosteal expanded bed. In the first experiment, small tissue expanders were placed and inflated subperiosteally in the mandible and subcutaneously in the breast. A fibrous connective tissue capsule was formed surrounding the implanted expanders. Periosteum was replaced by simple connective tissue during expansion. Capsule formation during STE was much more rapid than the subcutaneous expansion. In the subperiosteal group, a thick fibrous capsule consisting of coarse collagen fibers was observed one week after full inflation. Leaving the fully inflated subperiosteal expanders in place more than one month accelerated the resorption of the underlying bone. In the second experiment, one week after full expansion of the mandibular subperiosteal expander, the expander was removed and HA particles were implanted in the expanded bed. Despite marked augmentation with excessive amounts of HA particles, there was no deformity or infection of the grafts, which maintained their designed controur. The firm fibrous capsule formed by STE permitted consolida tion of HA particles easily and effectively, and prevented migration of the particles. Immobilization of the grafts was achieved within two months following implantation of the HA particles.

Composite hydroxylapatite (HA)/plaster alloplasts were studied for frontal and parietal cranioplasty. The experimental defects were created in 61 anesthetized cats. They were filled with a moist 2:1 mixture of durapatite/plaster or Interpore/plaster containing 0.85% potassium sulfate. After setting, the implant site was sutured. The filled defects were very firm by physical examination and showed little particle scatter by radiography. At the time this report was prepared only 43 of the cat skulls were available for examination. After sacrifice, postmortem visual examination (VE) of the skulls suggested that new bone had formed over some implants. In most implants, however, VE could not determine whether new bone had formed between the HA particles. Probing examination (PE) of the parietal implants with a periodontal explorer gave a better indication; the presence of new bone rather than soft tissue between the HA particles was confirmed by x-ray microanalysis. The ventral surfaces (VS) of the parietal implants showed greater degrees of bone formation by PE; only 12 of 43 parietal implants showed a high degree of bone formation on the dorsal surfaces (DS) by PE whereas 34 of 43 showed this on the VS. The highly significant difference (^3X) in the amount of bone formation on the VS compared with the DS suggests that this osteogenesis, like that observed in cranial trauma, may be stimulated by the dura which acts as a periosteum by supplying blood vessels to the implant.

Infrabony defects of 230 periodontal patients have been treated surgically by implantation. These lesions of alveolar bone, up to nineteen per patient, generally displayed pocket depths of at least 8mm and were associated with teeth showing pronounced mobility. Approximately 50% of these teeth could have ordinarily been condemned to extraction. In this study, scaling, root planing, and polishing were performed and patients were instructed in oral hygiene measures prior to surgical implantation. A 1:1 mixture of dense sintered hydroxylapatite(HA) particles (OrthoMatrix HA-500) with plaster of Paris (USG Medical Grade Calcium Sulfate Hemihydrate B, containing 0.85% K2SO4) was moistened with a minimum amount of saline. The mixture was then implanted into the dried defect. After setting, the operative site was closed with silk sutures. The plaster bound the HA particles in the defects and prevented particle straying which frequently occurs when they are implanted with saline alone or with other vehicles. There was an almost immediate and sustained diminution in tooth mobility at most implantation sites. Good retention of particles was seen on physical and radiographic examination of most defects for the length of the study (5 years). Overall, there was a marked reduction in pocket depth and improvement in tissue tone and texture. Less than 1% of the teeth at the implantation sites have been lost. No significant inflammation has been observed. Increased radiopacity and resistance to probing suggest bone formation in some implanted defects. Implantation of periodontal osseous defects with the biocompatible HA/plaster composite appears to result in the clinical cessation of progressive periodontal disease.

Inhibition of cortical and cancellous bone formation in glucocorticoid-treated OVX sheep

For an ideal osteochondral repair, it is important to facilitate zonal restoration of the subchondral bone and the cartilage, layer by layer. Specifically, restoration of the osteochondral junction and secure integration with adjacent cartilage could be considered key factors. The purpose of the present study was to investigate the feasibility of a combined material comprising a scaffold-free tissue-engineered construct (TEC) derived from synovial mesenchymal stem cells (MSCs) and a hydroxyapatite (HA) artificial bone using a rabbit osteochondral defect model. Osteochondral defects were created on the femoral groove of skeletally mature rabbits. The TEC and HA artificial bone were hybridized to develop a combined implant just before use, which was then implanted into defects (N=23). In the control group, HA alone was implanted (N=18). Histological evaluation and micro-indentation testing was performed for the evaluation of repair tissue. Normal knees were used as an additional control group for biomechanical testing (N=5). At hybridization, the TEC rapidly attached onto the surface of HA artificial bone block, which was implantable to osteochondral defects. Osteochondral defects treated with the combined implants exhibited more rapid subchondral bone repair coupled with the development of cartilaginous tissue with good tissue integration to the adjacent host cartilage when assessed at 6 months post implantation. Conversely, the control group exhibited delayed subchondral bone repair. In addition, the repair cartilaginous tissue in this group had poor integration to adjacent cartilage and contained clustered chondrocytes, suggesting an early osteoarthritis (OA)-like degenerative change at 6 months post implantation. Biomechanically, the osteochondral repair tissue treated with the combined implants at 6 months restored tissue stiffness, similar to normal osteochondral tissue. The combined implants significantly accelerated and improved osteochondral repair. Specifically, earlier restoration of subchondral bone, as well as good tissue integration of repair cartilage to adjacent host tissue could be clinically relevant in terms of the acceleration of postoperative rehabilitation and longer-term durability of repaired articular surface in patients with osteochondral lesions, including those with OA. In addition, the combined implant could be considered a promising MSC-based bio-implant with regard to safety and cost-effectiveness, considering that the TEC is a scaffold-free implant and HA artificial bone has been widely used in clinical practice.

Composite grafting of the maxillary sinus for placement of endosteal implants. A preliminary report of 48 patients

Prologned spaceflight results in bone loss in astronauts, but there is considerable individual variation. The goal of this rat study was to determine whether gender influences bone loss during simulated weightlessness. Six-month-old Fisher 344 rats were hindlimb unweighted for 2 wk, after which the proximal tibiae were evaluated by histomorphometry. There were gender differences in tibia length, bone area, cancellous bone architecture, and bone formation. Compared with female rats, male rats had an 11.6% longer tibiae, a 27.8% greater cortical bone area, and a 37.6% greater trabecular separation. Conversely, female rats had greater cortical (316%) and cancellous (145%) bone formation rates, 28.6% more cancellous bone, and 30% greater trabecular number. Hindlimb unweighting resulted in large reductions in periosteal bone formation and mineral apposition rate in both genders. Unweighting also caused cancellous bone loss in both genders; trabecular number was decreased, and trabecular separation was increased. There was, however, no change in trabecular thickness in either gender. These architectural changes in cancellous bone were associated with decreases in bone formation and steady-state mRNA levels for bone matrix proteins and cancellous bone resorption. In conclusion, there are major gender-related differences in bone mass and turnover; however, the bone loss in hindlimb unweighted adult male and female rats appears to be due to similar mechanisms.

The design of engineered bone substitutes takes biocompatibility and mechanical compatibility into account as prerequisite requirements. Titanium (Ti) and hydroxyapatite (HA) with chemical formula of Ca10(PO4)6(OH)2, show good biocompatibility and are known as biomaterials. To combine metal powder (Ti) and ceramic powder (HA) as a composite material with mechanical properties comparable to those of natural bones needs strategy. In this work, powder metallurgy process was employed to produce Ti-HA composites, with nominal HA powder contents in the range of 0-100 vol.%. Mixtures of Ti and HA powders were pressed in a rigid die. Sintering was performed in vacuum atmosphere. The as-sintered specimens were tested on biocompatibility in a human-osteoblast cells. It was found that processing and materials parameters, including compaction pressure, control the composite microstructures and mechanical properties. Laboratory bone tissue culturing showed that a bone tissue could grow on the artificial bones (sintered Ti-HA composites).

Bone Morphogenetic Protein (BMP) was extracted from bovine corticalbone and was bound to hydroxyapatite (HAP), which was synthesized by the wet method inorder to produce fine primary particles. Precipitate of the synthesized HAP was dried at 80°C, fired at 800°C for 3 hours, pulverized then sintered at 1200°C for 8 hours with the addition of resin beads, gclatin and hydrogenperoxide to make porous powder HAP and block HAP. For the combination of BMP and HAP, two different kinds of methods were performed.(Procedure 1) BMP was suspended in distilled water, and HAP was immersed in it, then lyophilized.(Procedure 2) BMP was solubilized in 0.01 M phosphate buffer (pH 7.2) with 6 M urea, and HAP was immersed in it, then dialyzed and lyophilized. HAP-BMP complexes were implanted in the thigh muscle pouch of mice (conventional male ddy, 5 weeks) which were sacrificed 3 weeks later to investigate the osteoinductive activity and biocornpatibility of the implants. All implanted HAP-BMP complex showed better osteoinductive activity than the implantation of BMP only, especially in the group made by prccedure 2, all implants induced fairly large amounts of new bone. No inflammatory cells were observed, and HAP and induced new bone were attached directly together without any connective tissues.

Mesenchymal stem cell (MSC)-based tissue-engineered construct (TEC)-hydroxyapatite (HAp) composites were developed by an alternate soaking process. The TEC derived from cultured synovial MSCs was alternately immersed in varying concentrations of CaCl(2)/Tris-HCl and Na(2)HPO(4)/Tris-HCl buffers, and HAp formation was analyzed by Fourier transform infrared spectroscopy (FT-IR), wide-angle X-ray diffraction, and scanning electron microscopy (SEM). These analyses clearly demonstrated HAp formation in the TEC. Specifically, SEM assessments showed that spherical HAp crystals of approximately 1 mum were directly formed on the surfaces of the cells and extracellular matrix (ECM) fibers. Cytotoxicity from exposure to calcium or phosphate buffers of >100 mM concentrations as assessed by LIVE/DEAD staining and total DNA assays was detected, but such cytotoxicity was not detected following exposure to concentrations of <50 mM. The HAp nanocrystals (ca. approximately 500 nm) were formed after 20 cycles in 10 mM calcium or phosphate buffers, and cell survival in the composites was confirmed. Moreover, preliminary implantation of TEC-HAp composites derived from rabbit synovial MSCs to rabbit osteochondral defects exhibited accelerated osteoinduction. These composites may be the first example of a hybrid material that consists of ECM, HAp nanocrystals, and living MSCs, and the TEC-HAp composite could be a unique and useful material for bone tissue engineering.

Summary Introduction. Hydroxyapatite (HAp) scaffolds have become an alternative to autologous bone grafts in orthopedic surgery, because it is possible to fill larger scale bone defects and of the decreased operation time and complication risks at the graft donor site, a promising method in bone regeneration is to load bone marrow - mesenchymal stromal cells (BM-MSCs) on to a HAp scaffold. Aim of the Study. The aim of our study is to compare subcutaneous tissue reaction of experimental animals to implantation of HAp and HAp that is coated with BM-MSCs. Materials and Methods. Autologous BM-MSCs were cultivated from crista iliaca dextra biopsy, 4 HAp ceramic implants were coated with BM-MSC and implanted in subcutaneous tissue on one side and non-coated HAp implants on the other side of the spine of 4 rabbits. Immunohistochemical staining of BM-MSC and connective tissue included TUNEL assay, NFkBp105, HSP 70k, Wnt1, TNF-α, VEGF, MMP-2 antibodies, microscoped at 400X magnification and analyzed semiquantitatively. Results. Routine staining with haemotoxilin and eosin demonstrated formation of granulation tissue around the HAp implant, which was more distinct on the control side. There was an increased number of NFκB p105 positive cells (fibroblasts, myocytes, endotheliocytes) on the experimental side (+++), in comparison to the control side (++). HSP70 and apoptosis index was decreased on the experimental side (++ and 60%), in comparison to the control side (+++ and 70%). Number of MMP2 positive structures was increased on the control side in the fibrous capsule (++), in comparison to the experimental side, where the result varied (0 - +) Conclusions. Cultured BM-MSC activity is partly limited due to the apoptosis, which is probably induced by environmental factors. BM-MSC coated HAp implant stimulates secretion of proliferation marker NFkBp105 in subcutaneous tissue, decreases cell stress, apoptosis and tissue degradation (decreased HSP 70, apoptotic cell count and MMP 2) to improve the local tissue quality and proving BM-MSC tissue protective effect

Two porous orbital implants available for clinical use in the anophthalmic socket are hydroxyapatite (HA) and porous polyethylene (PP). We examined the rate and the extent of fibrovascular ingrowth into these implants using histopathologic criteria in a rabbit model. Thirty-two New Zealand white rabbits underwent a unilateral enucleation with placement of a 14-mm spherical orbital implant. Twelve rabbits received HA, 12 small-pore PP, and 8 large-pore PP. The implants inserted were wrapped either in autologous sclera with and without anterior fenestrations or as unwrapped spheres. The implants were harvested at 6 and 12 weeks. The extent of fibrovascular ingrowth was assessed by determining the percentage of the cross-sectional area penetrated by fibrovascular tissue. On gross inspection, 12 implants (37.5%) were found to be exposed at harvesting; however, only two were grossly infected. The highest rate of exposure was found among the unwrapped implants. Wrapped versus unwrapped and fenestrated versus unfenestrated implants did not result in significant differences in the extent of vascularization. Hydroxyapatite implants were vascularized most rapidly. The small-pore PP implants did not become fully vascularized during the study, and yet complete vascularization was found in the large-pore PP at 12 weeks. The most intense areas of microscopic fibrovascular ingrowth were in the region where the extraocular muscles were in direct contact with the implant and at the posterior opening. Exposure of the implant was accompanied by chronic and acute inflammation. Both HA and large-pore PP spherical implants are capable of complete vascularization in this animal model.(ABSTRACT TRUNCATED AT 250 WORDS)

Osteophytes in osteoarthritis. Clinical aspects

Porous Titanium Implants with and without Hydroxyapatite Coating: A Biomechanical Study