Enhance Bone Ingrowth Research Articles

The influence hydroxyapatite nanoparticle shape and size on the properties of biphasic calcium phosphate scaffolds coated with hydroxyapatite–PCL composites

We developed a composite biphasic calcium phosphate (BCP) scaffold by coating a nanocomposite layer, consisting of hydroxyapatite (HA) nanoparticles and polycaprolactone (PCL), over the surface of BCP. The effects of HA particle size and shape in the coating layer on the mechanical and biological properties of the BCP scaffold were examined. Micro-computerized tomography studies showed that the prepared scaffolds were highly porous (∼91%) with large pore size (400–700 μm) and an interconnected porous network of ∼100%. The HA nanoparticle (needle shape)-composite coated scaffolds displayed the highest compressive strength (2.1 ± 0.17 MPa), compared to pure HA/β-TCP (0.1 ± 0.05 MPa) and to the micron HA – composite coated scaffolds (0.29 ± 0.07 MPa). These needle shaped scaffolds also showed enhanced elasticity and similar stress–strain profile to natural bone. Needle shaped coated HA/PCL particles induced the differentiation of primary human bone derived cells, with significant upregulation of osteogenic gene expression (Runx2, collagen type I, osteocalcin and bone sialoprotein) and alkaline phosphatase activity compared to other groups. These properties are essential for enhancing bone ingrowth in load-bearing applications. The developed composite scaffolds possessed superior physical, mechanical, elastic and biological properties rendering them potentially useful for bone tissue regeneration.

Cementless fixation of radial head implants is affected by implant stem geometry: An in vitro study

Background Metal radial head implants are widely used for the management of unreconstructible fractures. However, the effect of implant stem design on initial fixation and stability is unknown. This study determined the effects of radial head stem geometry on the initial stability of the uncemented implant. It was hypothesized that cortical contact and hence increased fixation would be achieved with an increased stem diameter, stem length and a tapered shape. Methods Eleven radii received five implants with differing stem geometries: short and long undersized, short and long optimally sized and short tapered. Inferiorly-directed compressive loads were applied successively to the anterior, posterior, medial and lateral edges of the implants. Maximum contralateral radial head “lift-off” was quantified by the distance between bone and implant surface markers. Findings The short and long undersized implants experienced greater micromotion with approximately 100 μm and 160 μm more lift-off respectively ( P < 0.02). The remaining optimally sized and tapered implants averaged 50 μm. There was greater motion for the undersized implants loaded at the lateral position ( P ⩽ 0.005). Interpretation This study shows that filling the diameter of the medullary canal is more important than filling the length of the canal. The taper did not offer any additional advantages compared to the straight stem, suggesting that reaming of bone to accept the taper did not produce enhanced initial purchase. If rigid initial implant fixation is desired with an uncemented radial head implant, a canal-filling stem reduces initial implant micromotion to less than 50 μm which may enhance bone ingrowth.

The incorporation of strontium and zinc into a calcium–silicon ceramic for bone tissue engineering

In this study we developed novel scaffolds through the controlled substitution and incorporation of strontium and zinc into a calcium–silicon system to form Sr–Hardystonite (Sr–Ca 2ZnSi 2O 7, Sr–HT). The physical and biological properties of Sr–HT were compared to Hardystonite (Ca 2ZnSi 2O 7) [HT]. We showed that Sr–HT scaffolds are porous with interconnected porous network (interconnectivity: 99%) and large pore size (300–500 μm) and an overall porosity of 78%, combined with a relatively high compressive strength (2.16 ± 0.52 MPa). These properties are essential for enhancing bone ingrowth in load-bearing applications. Sr–HT ceramic scaffolds induced the attachment and differentiation of human bone derived cells (HOB), compared to that for the HT scaffolds. Sr–HT scaffolds enhanced expression of alkaline phosphatase, Runx-2, osteopontin, osteocalcin and bone sialoprotein. The in vivo osteoconductivity of the scaffolds was assessed at 3 and 6 weeks following implantation in tibial bone defects in rats. Histological staining revealed rapid new growth of bone into the pores of the 3D scaffolds with the Sr–HT and HT, relative to the β-tricalcium phosphate (β-TCP). In vivo, HT and Sr–HT produced distinct differences in the patterns of degradation of the materials, and their association with TRAP positive osteoclast-like cells with HT appearing more resistant compared to both Sr–HT and β-TCP.

Comparison of enhancement of bone ingrowth into hydroxyapatite ceramics with highly and poorly interconnected pores by electrical polarization

The effects of electrical polarization of porous hydroxyapatite ceramics with different structures on bone ingrowth were compared. Two types of cylindrical porous hydroxyapatite ceramics with high and low interpore connection (hydroxyapatite-H and hydroxyapatite-L, respectively) were utilized in this study. Hydroxyapatite-H or hydroxyapatite-L with and without electrical polarization was implanted into the right or left femoral condyle of rabbits ( n = 10 in each group) and histological examination was performed 3 and 6 weeks after operation. Each cross-section was divided into three regions, outer, middle and inner region, and the percentage of total newly formed bone area/total area of each region (% bone area) was calculated. Bone ingrowth throughout the region of implant was significantly larger in the hydroxyapatite-H group than in the hydroxyapatite-L group. Electrical polarization was effective in enhancing bone ingrowth through all the pores of hydroxyapatite-H implant, however, this advantage was not apparent in the hydroxyapatite-L implant. It is suggested that enhanced bone ingrowth into hydroxyapatite porous bodies due to electrical polarization may be a cooperative interaction between the osteoconductivity of hydroxyapatite porous bodies and enhanced osteogenic cell activity induced by large charges stored on the pore surfaces.

Vitamin-D Binding Protein Does Not Enhance Healing in Rat Bone Defects: A Pilot Study

Vitamin D-binding protein (DBP) has an anabolic effect on the skeleton and reportedly enhances bone ingrowth. We used an in vivo critical bone defect model to determine whether local administration of DBP promotes bone defect healing. We created a 5-mm segmental bone defect in the radial shaft in a rat model. Forty-eight rats were assigned to eight groups: local application of 1 microg, 5 microg, 10 microg, or 50 microg DBP (DBP-1, DBP-5, DBP-10, DBP-50), autogenous bone marrow mononuclear cells with or without 10 microg DBP (BM-DBP-10, BM), 80 microg BMP-2 delivered in gelatin sponge (BMP-2), and the sham operated group. Radiographic evaluation, histological stains, and epifluorescence microscopy were performed. Grossly, all bone gaps of the BMP-2 group were solidly bridged by callus, while all those in the sham operated group remained unhealed by 9 weeks. Only one specimen of the BM-DBP-10 and DBP-50 groups and three specimens of the BM group were solidly healed; pseudarthroses occurred in all of the other specimens. Histological study and radiographs of the specimens showed similar results. We did not observe the enhanced bone healing reported in a previous study.

Enhanced bone ingrowth onto rhBMP-2-coated porous titanium implant placed in the distal femur of rabbits

Enhanced bone ingrowth onto rhBMP-2-coated porous titanium implant placed in the distal femur of rabbits

A novel biomimetic polymer scaffold design enhances bone ingrowth

There has been recent interest in treating large bone defects with polymer scaffolds because current modalities such as autographs and allographs have limitations. Additionally, polymer scaffolds are utilized in tissue engineering applications to implant and anchor tissues in place, promoting integration with surrounding native tissue. In both applications, rapid and increased bone growth is crucial to the success of the implant. Recent studies have shown that mimicking native bone tissue morphology leads to increased osteoblastic phenotype and more rapid mineralization. The purpose of this study was to compare bone ingrowth into polymer scaffolds created with a biomimetic porous architecture to those with a simple porous design. The biomimetic architecture was designed from the inverse structure of native trabecular bone and manufactured using solid free form fabrication. Histology and muCT analysis demonstrated a 500-600% increase in bone growth into and adjacent to the biomimetic scaffold at five months post-op. This is in agreement with previous studies in which biomimetic approaches accelerated bone formation. It also supports the applicability of polymer scaffolds for the treatment of large tissue defects when implanting tissue-engineering constructs. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009.

Porous implants as drug delivery vehicles to augment host tissue integration

The common premise of synthetic implants in the restoration of diseased tissues and organs is to use inert and solid materials. Here, a porous titanium implant was fabricated for the delivery of microencapsulated bioactive cues. Control-released transforming growth factor-beta1 (TGF-beta1) promoted the proliferation and migration of human mesenchymal stem cells into porous implants in vitro. At 4 wk of implantation in the rabbit humerus, control-released TGF-beta1 from porous implants significantly increased bone-to-implant contact (BIC) by 96% and bone ingrowth by 50% over placebos. Control-released 100 ng TGF-beta1 induced equivalent BIC and bone ingrowth to adsorbed 1 microg TGF-beta1, suggesting that controlled release is effective at 10-fold less drug dose than adsorption. Histomorphometry, scanning electron microscopy, and microcomputed tomography showed that control-released TGF-beta1 enhanced bone ingrowth in the implant's pores and surface. These findings suggest that solid prostheses can be transformed into porous implants to serve as drug delivery carriers, from which control-released bioactive cues augment host tissue integration.

Osseointegration in arthroplasty: can simvastatin promote bone response to implants?

Cementless fixation depends on bone ingrowth for long-term success. Simvastatin as a lipid lowering agent has been demonstrated to have osteoanabolic effects. This study was designed to measure the possible effect of simvastatin on implant osseointegration. Bilateral femoral implantation of titanium cylinders was performed in 20 rabbits. Blood lipid levels were measured pre- and postoperatively. Scanning electron microscopy (SEM) was used to measure the percentage of the surface of each implant in contact with bone and mechanical pull-out testing was performed. The blood lipid levels were significantly reduced in the simvastatin group. Histomorphometric examination revealed increased bone ingrowth and mechanical examination showed increased interface strength in the simvastatin group. Mechanical and histological data showed superior stability and osseous adaptation at the bone/implant interface for the simvastatin group. We conclude that simvastatin has potential as a means of enhancing bone ingrowth, which is a key factor in the longevity of cementless implants.

Characteristics of hydroxyapatite coated titanium porous coatings on Ti‐6Al‐4V substrates by plasma sprayed method

A porous metal coating applied to solid substrate implants has been shown, in vivo, to anchor implants by bone ingrowth. Calcium phosphate ceramics, in particular hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2), HA], are bioactive ceramics, which are known to be biocompatible and osteoconductive, and these ceramics deposited on to porous-coated devices may enhance bone ingrowth and implant fixation. In this study, bi-feedstock of the titanium powder and composite (Na(2)CO(3)/HA) powder were simultaneously deposited on a Ti-6Al-4V substrate by a plasma sprayed method. At high temperature of plasma torch, the solid state of Na(2)CO(3) would decompose to release CO(2) gas and then eject the molten Ti powder to induce the interconnected pores in the coatings. After cleaning and soaking in deionized water, the residual Na(2)CO(3) in the coating would dissolve to form the open pores, and the HA would exist at the surface of pores in the inner coatings. By varying the particle size of the composite powder, the porosity of porous coating could be varied from 25.0 to 34.0%, and the average pore size of the porous coating could be varied to range between 158.5 and 202.0 microm. Using a standard adhesive test (ASTM C-633), the bonding strength of the coating is between 27.3 and 38.2 MPa. By SEM, the HA was observed at the surface of inner pore in the porous coating. These results suggest that the method exhibits the potential to manufacture the bioactive ceramics on to porous-coated specimen to achieve bone ingrowth fixation for biomedical applications.

Effect of bone marrow grafting on the titanium porous-coated implant in bilateral total knee arthroplasty

Background and purpose Poor bone ingrowth into the porous coating of tibial components has been reported. We hypothesized that iliac marrow grafting might be useful to enhance bone ingrowth into a porous-coated implant. The first part of this study was to examine the presence of fibroblast colony-forming units (CFUF) containing osteogenic precursor cells in tibial bone marrow and iliac bone marrow. The second aim was to compare the clinical and radiographic results after bilateral total knee arthroplasty (TKA) with and without autologous bone marrow transplantation to the bone-implant interface.Methods Simultaneous bilateral TKA was performed in 21 patients with osteoarthritis. Aspirated iliac bone marrow was transplanted to the interface of one randomly selected porous-coated tibial component in each patient, and contralateral knees served as controls. All of the 21 patients were followed for 5 years.Results The average number of CFU-F was significantly lower in tibial marrow than in iliac marrow (p = 0.008). The final fluoroscopically-guided radiographs revealed a decrease in the number of knees with radiolucent lines after marrow grafting compared to those without grafting (p = 0.004).Interpretation Iliac bone marrow is useful as a bone grafting material to enhance the biological fixation in porous-coated implants.

Options for Acetabular Fixation Surfaces

Aseptic loosening is the most common cause for revision total hip arthroplasty (THA). Due to poor long-term results with cemented acetabular components, cementless implants that rely on biologic fixation became popular in the United States for both primary and revision procedures in the early 1980s. Cementless acetabular components used in THA have been reported to have superior radiographic performance compared with cemented fixation, although the optimal method of acetabular fixation remains controversial. Cementless acetabular components require initial implant stability to allow for bone ingrowth and remodeling into the acetabular shell, providing long-term durability of the prosthesis. Many improved implant materials are available to facilitate bone growth and remodeling, including the 3 most common surface treatments; fibermesh, sintered beads, and plasma spray coatings. Recently added to these are porous metal surfaces, which have increased porosity and optimal pore sizes when compared with titanium fibermesh. The most studied of these materials is the titanium fibermesh fixation surface, which has demonstrated a mechanical failure rate of 1% at 10 to 15 years. This technology utilizes the diffusion bonding process to attach fiber metal pads to a titanium substrate using heat and pressure. The sintered bead fixation surface offers a porous coating of various sizes of spherical beads, achieved by the sintering process, and has been shown to provide long-term fixation. While there are less long-term published data regarding the titanium plasma spray surface, its early results have provided evidence of its durability, even in the face of significant osteolysis. The most recently added alternative fixation surface is porous tantalum metal, which offers potentially greater bone ingrowth and bone graft incorporation due to its high porosity (80%) and low modulus of elasticity (3 MPa). Porous tantalum implants have shown early favorable clinical results and have been reported to have excellent bone graft incorporation of the acetabular component based on serial radiograph data at a minimum 1-year follow-up. Tritanium is a porous metal, which has emerged as a promising new surface technology for acetabular shells. While no clinical data are yet available, basic science research has demonstrated enhanced bone ingrowth and mechanical strength.

Bioceramics in Total Hip Arthoplasty: Hydroxyapatite Coating

Our objective is to describe the use of hydroxyapatite coatings in total hip arthroplasty. Hydroxyapatite enhances bone ingrowth and provides for a durable and lasting construct. The femoral component has performed well at 15-year minimum follow-up, with aseptic revision rates routinely less than 1%. Initial results on the acetabular side were disappointing. However, after redesign, a second-generation arc-deposited hydroxyapatite-coated cup is performing well at 4- to 7-year follow-up. Hydroxyapatite-coated implants have also been used successfully in the revision setting. Future applications include the use of hydroxyapatite coating as a means of delivering bone-enhancing drugs such as the bisphosphonates.

Enhanced bone ingrowth into hydroxyapatite with interconnected pores by Electrical Polarization

Hydroxyapatite (HA) ceramics are used as implants to repair damaged/removed bone, and negative or positive electrical polarization enhances osteoblast and decreases osteoclast activity, respectively, in vivo. We compared the ability of electrically polarized and non-polarized HA with interconnected pores (IPHA) implants to promote bone growth. Polarized or non-treated IPHAs were implanted into the right or left femoral condyle of rabbits (N = 10 in each group), and we performed histological examination, including enzymatic staining for osteoblasts and osteoclasts, 3 and 6 weeks after implantation. We observed improved bone ingrowth and increased osteoblast activity in polarized implants with complete bone penetration into polarized implants occurring as early as 3 weeks after surgery. In contrast, non-polarized implants were not fully ossified at 6 weeks after surgery. Furthermore, positively charged implant regions had decreased osteoclast activity compared to negatively charged or uncharged regions. We propose two different models to explain these observations.

Mechanical evaluation of implanted calcium phosphate cement incorporated with PLGA microparticles

In this study, the mechanical properties of an implanted calcium phosphate (CaP) cement incorporated with 20wt% poly (dl-lactic-co-glycolic acid) (PLGA) microparticles were investigated in a rat cranial defect. After 2, 4 and 8 weeks of implantation, implants were evaluated mechanically (push-out test) and morphologically (Scanning Electron Microscopy (SEM) and histology). The results of the push-out test showed that after 2 weeks the shear strength of the implants was 0.44+/-0.44MPa (average+/-sd), which increased to 1.34+/-1.05MPa at 4 weeks and finally resulted in 2.60+/-2.78MPa at 8 weeks. SEM examination showed a fracture plane at the bone-cement interface at 2 weeks, while the 4- and 8-week specimens created a fracture plane into the CaP/PLGA composites, indicating an increased strength of the bone-cement interface. Histological evaluation revealed that the two weeks implantation period resulted in minimal bone ingrowth, while at 4 weeks of implantation the peripheral PLGA microparticles were degraded and replaced by deposition of newly formed bone. Finally, after 8 weeks of implantation the degradation of the PLGA microparticles was almost completed, which was observed by the bone ingrowth throughout the CaP/PLGA composites. On basis of our results, we conclude that the shear strength of the bone-cement interface increased over time due to bone ingrowth into the CaP/PLGA composites. Although the bone-cement contact could be optimized with an injectable CaP cement to enhance bone ingrowth, still the mechanical properties of the composites after 8 weeks of implantation are insufficient for load-bearing purposes.

Use of Bisphosphonates to Improve the Durability of Total Joint Replacements

Total joint arthroplasty is very effective for improving the quality of life of patients with end-stage arthritis. Despite advances in materials, surgical technique, and rehabilitation regimens, joint replacements are still fraught with complications leading to their premature failure. Aseptic loosening and osteolysis are the primary causes of implant failure. Other reasons include early migration of components leading to instability, lack of ingrowth into implant porosities, and bone loss caused by stress shielding. Pharmaceutical agents used for preventing and managing postmenopausal osteoporosis (eg, bisphosphonates) may in the future play an important role in improving the long-term duration of joint arthroplasties. Early findings indicate that bisphosphonates upregulate bone morphogenetic protein-2 production and stimulate new bone formation. Because of their anabolic effect on osteoblasts, bisphosphonates have the potential to enhance bone ingrowth into implant porosities, prevent bone resorption under adverse conditions, and dramatically extend the long-term durability of joint arthroplasties. The long-term effects of bisphosphonate use on the mechanical properties of bone have not been adequately investigated. Along with improvements in implant design and material properties, bisphosphonates and other pharmaceutical agents may, in the near future, be part of the growing armamentarium that provides more durable joint arthroplasties.

Restoration of bone defect and enhancement of bone ingrowth using partially demineralized bone matrix and marrow stromal cells

This study aimed to investigate the capability of combining marrow stromal cells (MSC) and partially demineralized bone matrix (PDBM) to fill bone defect and enhance bone ingrowth using a canine non-weight-bearing gap model. Custom-made implants with 3mm gap between the porous surface and the host bone were used. The implants were inserted into the distal femurs of 25 mongrel dogs and the gaps were randomly assigned to be filled with culture-expanded autologous MSC-loaded PDBM, autograft, fresh-frozen allograft, PDBM alone, or nothing as controls. Histomorphometry using backscattered scanning electron microscopic examination, and mechanical push-out test were performed at 6 months after surgery. Histomorphometry showed that amounts of bone regeneration in the gap and bone ingrowth into the porous-coated surface in the MSC-loaded PDBM-treated group were comparable to those of autograft-treated group and were significantly greater than those of allograft-treated, PDBM-treated, or non-grafted groups. Mechanical test showed the same differences. The results of this study showed that combining PDBM and autologous culture-expanded MSC restored bone stock and enhanced bone ingrowth into the porous-coated area in a canine non-weight-bearing gap model. This combination may provide an option for reconstructing bone defect when we perform a cementless revision arthroplasty.

The biology of integration of the anterior cruciate ligament

The anterior cruciate ligament (ACL) is a short, stout, intra-articular, extrasynovial structure which acts to control rotational movements and anterior translation of the femur upon the fixed tibia.[1][1] Rupture is a traumatic event, often as a consequence of twisting upon the weight-bearing limb

Restoration of bone defect and enhancement of bone ingrowth using partially demineralized bone matrix and marrow stromal cells

Purpose This study aimed to investigate the capability of combining marrow stromal cells (MSC) and partially demineralized bone matrix (PDBM) to fill bone defect and enhance bone ingrowth using a canine non-weight-bearing gap model. Methods Custom-made implants with 3 mm gap between the porous surface and the host bone were used. The implants were inserted into the distal femurs of 25 mongrel dogs and the gaps were randomly assigned to be filled with culture-expanded autologous MSC-loaded PDBM, autograft, fresh-frozen allograft, PDBM alone, or nothing as controls. Histomorphometry using backscattered scanning electron microscopic examination, and mechanical push-out test were performed at 6 months after surgery. Results Histomorphometry showed that amounts of bone regeneration in the gap and bone ingrowth into the porous-coated surface in the MSC-loaded PDBM-treated group were comparable to those of autograft-treated group and were significantly greater than those of allograft-treated, PDBM-treated, or non-grafted groups. Mechanical test showed the same differences. Conclusion The results of this study showed that combining PDBM and autologous culture-expanded MSC restored bone stock and enhanced bone ingrowth into the porous-coated area in a canine non-weight-bearing gap model. This combination may provide an option for reconstructing bone defect when we perform a cementless revision arthroplasty.

Borate Glass Supports the In Vitro Osteogenic Differentiation of Human Mesenchymal Stem Cells

Bioactive ceramics have the ability to bond to surrounding bone and potentially enhance bone in-growth. Silicate based bioactive glasses and glass-ceramics, such as 45S5 bioactive glass, have been widely investigated for bone repair or as scaffolds for cell-based bone tissue engineering. Recent data have demonstrated that silica-free borate glasses also exhibit bioactive behavior and have been shown to convert to calcium phosphate at a remarkably rapid rate. Due to its relative novelty in biological applications, the cytocompatibity of borate glass is largely unknown. The objectives of this study were to investigate the cytocompatibility of borate glass by in vitro cell culture with human mesenchymal stem cells (hMSCs) and hMSC-derived osteoblasts (hMSC-Obs). The choice of hMSCs and hMSC-Obs is based on the rationale that both cell types are preferred cell lineages attached to bone implants. Borate glass particles with diameters of 212–355 μ m were loosely compacted into porous disks (porosity ≈ 40%) followed by sintering at 600°C. Partial or nearly complete conversion of the borate glass to calcium phosphate (Ca-P) material was achieved by soaking the disks for 1 day or 7 days in a 0.25 molar K2HPO4 solution at 37°C and at pH of 9.0. Bone marrow derived hMSCs and hMSC-Obs adhered to the pores of borate glass disks. Upon 2 week incubation of cell-seeded borate glass disks, hMSC-Obs markedly synthesized alkaline phosphatase, an early osteogenic marker. These data provide preliminary evidence of cytocompatibility of borate glass and its role in supporting the osteogenic differentiation of mesenchymal stem cells.