The effect of hydroxyapatite coating on bone growth into porous titanium alloy implants

In rabbits and goats, test implants with a porous surface of two layers of Tl-6A;-4V beads were examined at intervals for bond strength with bone. Half of the implants were coated with hydroxyapatite by plasma spray. The bonding strength with bone in the coated specimens was about four times greater than that of the uncoated specimens at two weeks, and twice as strong at six weeks. Twelve weeks after implantation, the strengths were similar. The hydroxyapatite coating of the beads provided earlier and stronger fixation.     

Influence of disodium (1-hydroxythylidene) diphosphonate on bone ingrowth into porous,titanium fiber-mesh implants

The influence of disodium (1-hydroxythylidene) diphosphonate on the bonding between bone and porous, titanium fiber-mesh implants was studied. Rectangular, porous, titanium fiber-mesh implants (15 × 10 × 2.4 mm) were implanted into the tibial bone of mature male rabbits. The rabbits were divided into six groups. Disodium diphosphonate was administered daily by subcutaneous injection to groups 1–5. Groups 1–4 received doses of 5.0, 2.5, 1.0, and 0.1 mg per kilogram of body weight per day for 8 weeks, respectively. Group 5 received a dose of 5 mg per kilogram of body weight per day for 4 weeks. Group 6 (control group) was given saline injections. At 8 weeks after implantation, the rabbits were killed. The tibiae containing the implants were dissected out and subjected to detachment tests. The failure load, when an implant became detached from the bone or when the bone itself broke, was measured. The interface of the bone and implant was investigated by Giemsa surface staining and contact microradiography. Giemsa surface staining and contact microradiography showed that porous implant bonding to bone tissue was inhibited by a high dose of disodium diphosphonate in groups 1, 2, and 5. Soft tissue was observed at the interface. In groups 3, 4, and 6, bone tissue ingrowth was observed at the interface between the porous implant and bone tissue. Growth of bone into the porous fiber-mesh implant of a cementless prosthesis is possible if a low dose of diphosphonate below 1.0 mg per kilogram of body weight is given subcutaneously     

Bone ingrowth into weight-bearing porous fiber titanium implants. Mechanical and biochemical correlations

Bone ingrowth into weight-bearing porous fiber Ti-6Al-4V implants in rat tibias was assessed for the amount, composition, and mineralization rate 3, 12, and 26 weeks after implantation. The data were compared with the ipsi- and contralateral metaphyseal controls and related to the ultimate bending stresses of the distal bone/implant interfaces. From the 3rd to the 12th week there was rapid bone ingrowth and also marked decline in mineralization rate of the ingrowing bone. After 12 weeks the implants were macroscopically pervaded by bone. The ultimate bending stresses increased from the 3rd to the 12th week and reached 45% of that of controls after 26 weeks. There was a linear proportionality between the amount of bone ingrowth and interfacial strength but a curvilinear relationship between bone maturity in terms of calcium/hydroxyproline and calcium/phosphorous ratios and interfacial strength. Stepwise multiple regression analysis showed that the interfacial strength depends on the amount and the maturity of the ingrown bone. Compared with the calcium/hydroxyproline ratio, the calcium/phosphorous ratio was an unreliable predictor of interfacial strength.     

The effect of impaction and a bioceramic coating on bone ingrowth in porous titanium particles

Background and purpose Porous titanium (Ti) particles can be impacted like cancellous allograft bone particles, and may therefore be used as bone substitute in impaction grafting. We evaluated the effect of impaction and of a thin silicated biphasic calcium phosphate coating on osteoconduction by Ti particles.

Methods The bone conduction chamber of Aspenberg was used in goats and filled with various groups of coated or uncoated small Ti particles (diameter 1.0–1.4 mm). Impacted allograft bone particles and empty chambers were used in control groups. Fluorochromes were administered at 4, 8, and 12 weeks. Maximum bone ingrowth distance was evaluated by histomorphometric analysis.

Results Histology of Ti particle graft cylinders showed a dense matrix with narrow inter-particle and intra-particle pores (< 100 μm), occluding the lumen of the bone chamber. Bone ingrowth distances gradually increased with time in all groups. Maximum bone ingrowth distance was higher in originally empty chambers than those with allograft bone particles (p = 0.01) and Ti particles (p < 0.001). Maximum bone ingrowth in allograft bone particles was higher than in all Ti groups (p ≤ 0.001). Impaction reduced osteoconduction and the coating partially compensated for the negative effect of impaction, but these differences were not statistically significant. No osteolytic reactions were found.

Interpretation Osteoconduction in the bone conduction chamber was reduced more by the insertion of small Ti particles than by insertion of small allograft bone particles. The osteoconductive potential of porous Ti particles should be studied further with larger-sized particles, which may allow bone ingrowth after impaction through larger inter-particle pores.     

The effect of impaction and a bioceramic coating on bone ingrowth in porous titanium particles

Background and purpose

Porous titanium (Ti) particles can be impacted like cancellous allograft bone particles, and may therefore be used as bone substitute in impaction grafting. We evaluated the effect of impaction and of a thin silicated biphasic calcium phosphate coating on osteoconduction by Ti particles.

Methods

The bone conduction chamber of Aspenberg was used in goats and filled with various groups of coated or uncoated small Ti particles (diameter 1.0–1.4 mm). Impacted allograft bone particles and empty chambers were used in control groups. Fluorochromes were administered at 4, 8, and 12 weeks. Maximum bone ingrowth distance was evaluated by histomorphometric analysis.

Results

Histology of Ti particle graft cylinders showed a dense matrix with narrow inter-particle and intra-particle pores (< 100 μm), occluding the lumen of the bone chamber. Bone ingrowth distances gradually increased with time in all groups. Maximum bone ingrowth distance was higher in originally empty chambers than those with allograft bone particles (p = 0.01) and Ti particles (p < 0.001). Maximum bone ingrowth in allograft bone particles was higher than in all Ti groups (p ≤ 0.001). Impaction reduced osteoconduction and the coating partially compensated for the negative effect of impaction, but these differences were not statistically significant. No osteolytic reactions were found.

Interpretation

Osteoconduction in the bone conduction chamber was reduced more by the insertion of small Ti particles than by insertion of small allograft bone particles. The osteoconductive potential of porous Ti particles should be studied further with larger-sized particles, which may allow bone ingrowth after impaction through larger inter-particle pores.Allograft bone impaction grafting restores the original bone stock (Halliday et al. 2003). Morselized cancellous allograft bone chips remain the gold standard material, but they have their limitations such as limited availability, risk of pathogen transmission, and religious considerations (Conrad et al. 1995, Galea et al. 1998). Calcium phosphate particles have been used successfully with good long-term clinical results (Oonishi et al. 2008). However, bioceramics show inferior handling characteristics (Bolder et al. 2002, van Haaren et al. 2005), and accelerated resorption could compromise construct stability (Ninomiya et al. 2001).Porous commercially pure titanium (Ti) particles are not resorbed by osteoclasts; thus, the stability of the graft layer is not reduced by remodeling. Long-term stability is probably dependent on ingrowth of fibrous tissue and bone. A canine model and a human retrieval model have shown that non-impacted, non-coated small Ti particles are osteoconductive when they are used in the femur in combination with an uncemented, vibration-based technique to insert the stem into the bed of Ti particles (Alffram et al. 2007, Turner et al. 2007). We intend to use larger and highly porous Ti particles with a different surgical technique: cemented impaction grafting of the acetabulum and femur. Impaction of large Ti particles creates a graft layer with good entanglement and primary stability (Aquarius et al. 2009, Walschot et al. 2010). However, we do not know whether impacted Ti particles allow tissue ingrowth like non-impacted Ti particles: impaction poses a threat to the osteoconduction of a non-degradable material like Ti particles by obliteration of ingrowth spaces, which is even observed with a resorbable material like allograft bone (Tägil and Aspenberg 1998, Jeppsson et al. 2003). Thus, we evaluated the effect of impaction on osteoconduction by small Ti particles in a bone conduction chamber (Aspenberg et al. 1996) in goats. We expected that the addition of a thin sol-gel-formed silicated calcium phosphate coating would favor osteoconduction of this porous titanium graft material (Nguyen et al. 2004).     

Effects of hydroxyapatite tricalcium phosphate coating and intracancellous placement on bone ingrowth in titanium fibermetal implants

The purpose of this study was to compare the host—bone response to hydroxyapatite/tricalcium phosphate (HA/TCP)-coated and noncoated titanium fibermetal implants placed in a load-sharing cancellous bone environment of the distal femurs of rabbits. The influence of implantation site was also investigated by comparing these intracancellous implants with intramedullary implants evaluated in a previous study. Three parameters were measured: percentage implant perimeter surface length in contact with new bone, percentage internal fibermetal surface length in contact with ingrown bone, and percentage of available pore space filled with bone. The HA/TCP coating significantly accelerated and increased bone ongrowth, new bone formation on the perimeter and internal surface of the implants. This effect was evident as early as 2 weeks after implantation. In contrast, there was no difference between HA/TCP-coated and noncoated implants in the bone ingrowth parameter, percentage of available pore space filled with bone, or pull-out strength. Scanning electron microscopy in the backscatter mode demonstrated that new bone formed directly onto the HA/TCP-coated fibers and did not usually form directly on noncoated fibers. Analysis of fluorochrome labeling revealed that bone formation in weeks 1 through 4 was primarily woven and there-after lamellar. Compared with intramedullary placement, intracancellous placement significantly accelerated the apposition of bone to the perimeter and internal surface of HA/TCP-coated implants and both accelerated and increased bone ingrowth as a percentage of available pore volume. These data show that the host response to titanium fibermetal implants is influenced both by HA/TCP coating and by the implantation site.     

Osseointegration study of porous nitinol versus titanium orthopaedic implants

The functionality of a new metallic interbody fusion implant manufactured out of porous nitinol (PNT) was evaluated in sheep and compared to a conventional titanium (TiAIV) intervertebral cage packed with autologous iliac crest bone. Both device types were implanted at two non-contiguous intervertebral lumbar sites. The objective was to evaluate the osseointegration capacity after 3, 6 and 12 months of implantation in the presence of these two implant types subjected to the same mechanical loads. Two-dimensional radiology, computer tomography and histology were used as techniques of parameter evaluation. The results indicated that PNT obtained a better intervertebral osseointegration capacity compared to the TiAlV cage. The functional difficulties of the titanium implant were related to its instability at the implantation site possibly due to a biofunctionality problem. The biocompatibility of both implants seemed comparable, however.     

Bioactive porous titanium: an alternative to surgical implants

Abstract:  Porous titanium implants have been used to improve implant–bone attachment by the ingrowth of bone tissue within the porous structure. Despite the efficient bone adhesion of porous titanium implants, chemical bonds are required at bone–implant interface. These implants can become bioactive by a biomimetic precipitation process. The aim of this work was to enhance the bioactivity of pure porous titanium implants by biomimetic process. The samples immersed in a simulated body fluid promoted the nucleation and growth of calcium phosphate (Ca-P) crystals, such as hydroxyapatite (Hap), on the material surface. Scanning electron microscopy, energy dispersive spectroscopy, and Fourier transform infrared spectroscopy analyses revealed that a Ca-P deposition occurred without the need of pretreatments to improve the surface bioactivity. This present study indicates the potential for growing a bone-like Hap layer on porous titanium implants by biomimetic processes.     

Enhanced bone ingrowth and fixation strength with hydroxyapatite-coated porous implants

The effect of a hydroxyapatite (HA) coating on the interface attachment strength, rate of development of attachment strength, and degree of bone ingrowth of porous implants was investigated. Implants with ideal surgical fits and those having interface gap spaces were evaluated using femoral transcortical and intramedullary models. The application of a thin HA coating to porous implants significantly enhanced both interface attachment strength and bone ingrowth. The rate of development of interface strength and bone ingrowth was also more rapid with the HA-coated system. There was no evidence of any disruption, loss, or resorption of the HA coating.     

Platelet concentrate increases bone ingrowth into porous hydroxyapatite

Platelets contain growth factors that are believed to stimulate early fracture repair. Autologous platelets can be sequestered, concentrated, and mixed with thrombin to yield a so-called autologous growth factor gel, which might enhance bone repair or bone graft incorporation. The effect of this platelet concentrate on total tissue and bone ingrowth into porous coralline hydroxyapatite was studied in a bone chamber rat model. Chambers with the platelet concentrate showed a significant increase in bone and total tissue ingrowth distance compared to untreated controls, indicating a platelet concentrate might enhance the clinical performance of porous hydroxyapatite in bone replacement.     

Observations on the effect of movement on bone ingrowth into porous-surfaced implants

Although porous-surfaced orthopedic implants have been designed for fixation by bone ingrowth, there is clinical evidence that this does not always occur. Initial implant movement relative to host bone can result in attachment by a nonmineralized fibrous connective tissue layer. The ranges of movement that result in either bone or fibrous connective tissue fixation are observed in dogs in two independent studies. Experimentally, bone ingrowth can occur in the presence of some movement, albeit very small (up to 28 mu), while excess movement (150 mu or more) can result in attachment by mature connective tissue ingrowth.     

Progression of human bone ingrowth into porous-coated implants: Rate of bone ingrowth in humans

We report the measured progression of human cancellous bone ingrowth into load-bearing porous-coated titanium implants over 5 time periods (0,3,6, 9, and 12 months). There was a statistically significant progression of bone ingrowth into the implants over a 9-month period, but the 9- and 12-month data were not different. Investigators are advised to analyze time “0” implants in order to distinguish mechanical impaction of bone from the biological process of bone ingrowth.     

The effect of demineralized bone matrix gel on bone ingrowth and fixation of porous implants

The presence of demineralized bone matrix (DBM) gel did not enhance or accelerate attachment strength or bone ingrowth and resulted in a significant decrease in implant interface attachment strength at 3 weeks. Hydroxyapatite (HA) coating resulted in significant increases in interface shear strength and bone ingrowth compared with non-HA-coated porous implants at all time periods. The HA-coated implants achieved greater attachment strength and bone ingrowth at earlier time periods and maintained greater attachment strength at long-term periods. The results of this study indicate that in the presence of a good bone-implant interference fit, there is no beneficial effect in applying DBM gel to a porous-coated or HA-coated porous implant surface. The small amount that can be applied and the degree of osteoinductivity of DBM seem to preclude it from having a significant biologic effect.     

Skeletal fixation of implants by bone ingrowth into surface pores

Summary An alternative skeletal fixation by bone ingrowth into porous coatings has been studied.Stainless steel fiber coatings using different fiber diameters (50–100 m) and different pore sizes have been tested.Plugs, intramedullary rods and various types of knee prostheses have been implanted in dogs in non functional and also in functional loading conditions.Histological and mechanical evaluation of the bone implant interface has been performed.Consistent bone ingrowth was observed for implants in non functional conditions if the pore size exceeded 70 m. Ingrowth in functional loading conditions requires rigid initial stability of the implant and intimate contact of implantcoating and surrounding bone tissue.Supported by Grant No. 3.0071.76: Fonds voor Geneeskundig Wetenschappelijk Onderzoek     

富血小板血浆促纤维多孔钛颈椎椎间融合器中骨长入作用

目的观察富血小板血浆(PRP)促进纤维多孔钛椎体间融合器(fiber porous titanium Cage,FPT Cage)的骨长入作用。方法健康成年比格犬6只,体质量12.5~15.0 kg,雌雄各3只。取比格犬前肢外周静脉血20.0 m L,采用二次离心法制备PRP,同时对外周静脉血及PRP行血小板计数。行颈椎前路C4/C5/C6椎间盘切除FPT Cage椎间融合术,C4/C5节段单纯使用FPT Cage,C5/C6节段采用激活的PRP浸泡的FPT Cage。术后4个月处死比格犬后行硬组织切片检查,观察C4/C5/C6节段FPT Cage中骨长入的情况。结果 C4/C5节段椎间隙FPT Cage-骨界面附近可见少量软骨细胞和成骨细胞;FPT Cage中央孔隙内发现少量成骨细胞,类骨质较少,大部分孔隙内仍然为纤维组织。C5/C6节段椎间隙FPT Cage-骨界面可见成熟骨组织形成;FPT Cage边缘孔隙内可见骨组织长入;FPT Cage中央孔隙内发现大量成骨细胞;大部分中央孔隙内为类骨组织,少部分中央孔隙内仍然为纤维组织。结论在比格犬体内实验研究中,复合PRP可以促进FPT Cage内的骨长入。     

Low-intensity pulsed ultrasound increases bone ingrowth into porous hydroxyapatite ceramic

Synthetic porous ceramic made of hydroxyapatite (HA) has been used as a bone graft substitute. In the present study we investigated whether low-intensity pulsed ultrasound (LIPUS) accelerates bone ingrowth into the pores of HA ceramic. Application of LIPUS did not mechanically weaken porous ceramic that was immersed in water in vitro. In vivo experiments using rabbits showed that LIPUS application for 2 weeks significantly increased osteoblast number and bone area in the central part of the porous HA ceramic implanted in the femoral condyle in comparison with similarly implanted HA ceramic that was not exposed to LIPUS. LIPUS application for 3 weeks significantly increased mineralized tissue volume and mineral content in the porous HA ceramic. Wound healing assays revealed increased migration of MC3T3-E1 cells as a result of LIPUS treatment, partly accounting for the increased osteoblast number. Use of porous HA ceramic combined with LIPUS may be a promising treatment for filling large bone defects in a clinical setting.     

Tissue ingrowth into titanium and hydroxyapatite-coated implants during stable and unstable mechanical conditions.

Lack of initial mechanical stability of cementless prostheses may be responsible for fibrous tissue fixation of prosthetic components to bone. To study the influence of micromovements on bony ingrowth into titanium alloy (Ti) and hydroxyapatite (HA)-coated implants, a loaded unstable device producing movements of 500 microns during each gait cycle was developed. Mechanically stable implants served as controls. The implants were inserted into the weight-bearing regions of all four femoral condyles in each of seven mature dogs. Histological analysis after 4 weeks of implantation showed a fibrous tissue membrane surrounding both Ti and HA-coated implants subjected to micromovements, whereas variable amounts of bony ingrowth were obtained in mechanically stable implants. The pushout test showed that the shear strength of unstable Ti and HA implants was significantly reduced as compared with the corresponding mechanically stable implants (p less than 0.01). However, shear strength values of unstable HA-coated implants were significantly greater than those of unstable Ti implants (p less than 0.01) and comparable to those of stable Ti implants. The greatest shear strength was obtained with stable HA-coated implants, which was threefold stronger as compared with the stable Ti implants (p less than 0.001). Quantitative determination of bony ingrowth agreed with the mechanical test except for the stronger anchorage of unstable HA implants as compared with unstable Ti implants, where no difference in bony ingrowth was found. Unstable HA-coated implants were surrounded by a fibrous membrane containing islands of fibrocartilage with higher collagen concentration, whereas fibrous connective tissue with lower collagen concentration was predominant around unstable Ti implants. In conclusion, micromovements between bone and implant inhibited bony ingrowth and led to the development of a fibrous membrane. The presence of fibrocartilage and a higher collagen concentration in the fibrous membrane may be responsible for the increased shear strength of unstable HA implants. Mechanically stable implants with HA coating had the strongest anchorage and the greatest amount of bony ingrowth.     

Effects of estrogen deficiency on the growth of tissue into porous titanium implants

The effect of systemic deficiency of estrogen on the growth of tissue into porous titanium-fiber implants was studied in ovariectomized Beagle dogs. Five dogs were ovariectomized and five dogs had a sham operation. After waiting four months to allow the levels of circulating estrogen to decline, a titanium-alloy implant that contained four surface pads of titanium-alloy mesh was implanted in the proximal part of the humerus of each dog bilaterally. Two months later, the implants were harvested and subjected to a mechanical push-out test and quantitative histological study. The push-out strength of the implants from the ovariectomized dogs was 31 per cent less than in the control animals. Ovariectomy caused no difference in the amount of ingrowth of bone but resulted in a significant increase in the amount of fibrous connective tissue within the porous pads. The presence of this fibrous tissue appeared to have an important effect on bone-implant fixation: in the control dogs, strength correlated positively with ingrowth of bone and negatively with ingrowth of fibrous tissue, whereas in the ovariectomized dogs, strength correlated positively with ingrowth of fibrous tissue and not at all with ingrowth of bone.     

rhBMP-2诱导界面骨长入中空金属植入物的初步实验研究

目的：探讨界面骨质经孔洞长入中空金属植入物及以rhBMP-2/载体复合物诱导增效的可能性。方法：以兔胫骨干骺端植入集骨器（bone harvest chamber,BHC)为动物模型，在其中分别加载rhBMP-2和rhBMP-2/透明质酸钠凝胶（Healon GV)复合物10μl（均含rhBMP-2 1mg)，并以单纯置入等量Healon GV和注射用水作为对照。2,4,6周取出BHC中组织，行组织学观察并行MMA包埋不脱钙骨切片，计算机图像分析测算小梁骨总体积密度（trabecular bone volume,TBV)进行骨形态计量学分析，组间比较成骨量。结果：rhBMP-2/Healon GV复合物组和rhBMP-2组于植入2周后BHC内均已有交织骨形成，前者骨质较密集；4周时为成熟骨小梁间以髓样组织填充；6周时骨质更为密集。而Healon GV组和注射用水组4周的表现与前两组2周时接近，6周时才形成成熟的骨小梁和髓样组织。结论：界面骨质可通过也洞长入中空金属植入物的空腔内并形成成熟的骨质，rhBMP-2可促进骨长入效应及成骨质量，rhBMP-2载体Healon GV不影响且可增强骨诱导作用。     

Effect of alendronate on bone ingrowth into porous tantalum and carbon fiber interbody devices

Recent studies have reported that bisphosphonates reduce the resorption of grafted bone and inhibit bone resorption at a bone-implant interface. However, it is not known whether bisphosphonates affect bone ingrowth into porous biomaterial or spine fusion interbody devices with an autograft. In this study, 18 pigs (9 in each group) underwent anterior intervertebral lumbar arthrodeses at L2-3, L4-5 and L6-7. Each level was randomly allocated to one of the 3 implants: a solid piece of porous tantalum (Hedrocel), a porous tantalum ring or a carbon fiber cage both packed with an autograft. Alendronate was given orally to one of the groups. The radiographic and histological findings in the two groups 3 months after operation were similar in these devices. Histological examination showed that the original graft was entirely replaced by new trabecular bone in both groups. On histomorphometric analysis, the bone volume fraction, both inside the central hole of porous tantalum ring and in the porous tantalum, was larger in the pigs given alendronate than in the controls, but the fraction inside and around the central hole of the carbon fiber cage was not affected by this treatment. Short-term alendronate treatment, in a relatively low dose, does not impair the formation of new bone, but increases bone ingrowth into the central hole of the porous tantalum ring and the pores of the porous tantalum in this porcine model. This may be an effective way to enhance early biologic fixation of porous intervertebral implants.