Improved Bone Ingrowth Research Articles

Ti6Al4V Implants with Dense-Trabecular Bilayer Morphology for Bone Ingrowth: Synergy of Green Net Shaping and Sacrificial Templating.

Stress shielding in dental and orthopedic implants is a long-standing hurdle, and trabecular porous architecture to improve bone ingrowth is deemed to be a potential solution. Fabricating Ti6Al4V components with dense-porous bilayer structures is complicated with limited lab-scale and commercial success. Here, a green dough-forming technique with metal powders is successfully explored to develop heterogeneous structures with a monolith-like dense-porous interface. The porous region achieved 70% porosity with a 25 MPa compressive strength comparable to human cancellous bone. Due to its simplicity and versatility, this process is a promising solution for developing and mass-manufacturing customized designs for bone-related implants with improved bone ingrowth and osseointegration.

Mechano-driven intervertebral bone bridging via oriented mechanical stimulus in a twist metamaterial cage: An in silico study

Stiffer cages provide sufficient mechanical support but fail to promote bone ingrowth due to stress shielding. It remains challenging for fusion cage to satisfy both bone bridging and mechanical stability. Here we designed a fusion cage based on twist metamaterial for improved bone ingrowth, and proved its superiority to the conventional diagonal-based cage in silico. The fusion process was numerically reproduced via an injury-induced osteogenesis model and the mechano-driven bone remodeling algorithm, and the outcomes fusion effects were evaluated by the morphological features of the newly-formed bone and the biomechanical behaviors of the bone-cage composite. The twist-based cages exhibited oriented bone formation in the depth direction, in comparison to the diagonal-based cages. The axial stiffness of the bone-cage composites with twist-based cages was notably higher than that with diagonal-based cages; meanwhile, the ranges of motion of the twist-based fusion segment were lower. It was concluded that the twist metamaterial cages led to oriented bone ingrowth, superior mechanical stability of the bone-cage composite, and less detrimental impacts on the adjacent bones. More generally, metamaterials with a tunable displacement mode of struts might provide more design freedom in implant designs to offer customized mechanical stimulus for osseointegration.

Feasibility evaluation of a new lattice for porous surface design in additive manufacturing medical implants under interfacial tensile bonded testing

Porous titanium implant surfaces fabricated with suitable porosity and size using additive manufacturing (AM) can enhance bone–implant stability. There is a critical need to understand the biomechanical performance of porous (lattice) type implants to improve bone ingrowth efficiency and interfacial bonded strength. This study proposes a new lattice type implant with appropriate/favorable physiological environment within the lattice for bone ingrowth and increasing bone-implant bonded strength. A unit (1mm3 cube) YM lattice with 65 % porosity and average pore size of 750 µm was designed as a 3D spherical structure to increase bone cell growth capacity with multiple-corners for accepting cell clustering and the transport of fluids, nutrients and the expelling of impurities between these interconnected through-holes. The finite element (FE) sub-modeling technique was used to investigate the implant-bone interface micro mechanical behavior, to include lattice pillars, bone within/around lattices for four different lattice types with YMU, YMR (YM lattice without deformation and with 30 % deformation), DU and DR (Diamond lattice without deformation and with 30 % deformation). The DU and YMR lattice implants (6 × 6 × 3 mm3 block) were selected and fabricated using a Ti6Al4V AM (each n = 5) and implanted into the distal right femurs of 10 rabbits for 8 weeks for observation. The interface tensile bonded strength test was performed after the rabbits were sacrificed. No lattice implant slipped in any of the rabbits after surgery. This confirms postoperative radiographs. The test results showed that both the bonded force and strength of the YMR lattice were found significantly higher than those of DU. The corresponding values were 113.14 ± 21.96 N and 5.39 ± 1.04 MPa for the YMR lattice and 41.41 ± 15.32 N and 1.97 ± 0.73 MPa for the DU lattice. This study proposed a YMR lattice that presented a suitable bone ingrowth environment and interfacial bond strength test for surface porous design for the AM medical implant.

DAR 16-II Primes Endothelial Cells for Angiogenesis Improving Bone Ingrowth in 3D-Printed BCP Scaffolds and Regeneration of Critically Sized Bone Defects.

Bone is a highly vascularized tissue and relies on the angiogenesis and response of cells in the immediate environmental niche at the defect site for regeneration. Hence, the ability to control angiogenesis and cellular responses during osteogenesis has important implications in tissue-engineered strategies. Self-assembling ionic-complementary peptides have received much interest as they mimic the natural extracellular matrix. Three-dimensional (3D)-printed biphasic calcium phosphate (BCP) scaffolds coated with self-assembling DAR 16-II peptide provide a support template with the ability to recruit and enhance the adhesion of cells. In vitro studies demonstrated prompt the adhesion of both human umbilical vein endothelial cells (HUVEC) and human mesenchymal stem cells (hMSC), favoring endothelial cell activation toward an angiogenic phenotype. The SEM-EDS and protein micro bicinchoninic acid (BCA) assays demonstrated the efficacy of the coating. Whole proteomic analysis of DAR 16-II-treated HUVECs demonstrated the upregulation of proteins involved in cell adhesion (HABP2), migration (AMOTL1), cytoskeletal re-arrangement (SHC1, TMOD2), immuno-modulation (AMBP, MIF), and morphogenesis (COL4A1). In vivo studies using DAR-16-II-coated scaffolds provided an architectural template, promoting cell colonization, osteogenesis, and angiogenesis. In conclusion, DAR 16-II acts as a proactive angiogenic factor when adsorbed onto BCP scaffolds and provides a simple and effective functionalization step to facilitate the translation of tailored 3D-printed BCP scaffolds for clinical applications.

Novel nano-hydroxyapatite coating of additively manufactured three-dimensional porous implants improves bone ingrowth and initial fixation.

Electron beam melting (EBM) has been used to fabricate three-dimensional (3D) porous Ti-6Al-4V surfaces for acetabular cups in total hip arthroplasty. However, there are radiographic concerns regarding poor implant fixation and bone ingrowth around electron beam melted (EBMed) 3D porous cups. We hypothesize that nano-hydroxyapatite (nHA) coating can promote bone ingrowth and thus decrease the occurrence of radiolucent lines around EBMed 3D porous cups. This study aimed to investigate the effect of a novel nHA coating on the biological performance of EBMed 3D porous implants in a beagle transcortical model. Low-porosity (control) and high-porosity 3D porous Ti-6Al-4V implants were manufactured using EBM. Half of the high-porosity implants were coated with nHA without clogging the 3D pores. Implants were inserted into the femoral diaphysis of the beagles. The beagles were euthanized at 4, 8, and 12 weeks postoperatively, and push-out testing was performed. Bone ingrowth was evaluated by histological analysis. Although the increase in porosity alone had no effect on biological behavior, the addition of nHA to high-porosity 3D implants significantly improved early bone fixation and bone ingrowth into the deep region of porous structures compared to low-porosity implants. This is the first report of a novel nHA coating that improved bone ingrowth into the deeper regions of 3D porous implants, which can prevent the occurrence of radiolucent lines around EBMed 3D porous cups.

Corrosion Behavior of Selective Laser Melting (SLM) Manufactured Ti6Al4V Alloy in Saline and BCS Solution.

The frequency of surgeries involving the use of metal implants in orthopedic medicine to replace degenerative or fractured joints is increasing, and it is therefore important to optimize the lifespan and quality of these implants. Advances in additive manufacturing (AM), or 3D printing, are creating new opportunities to personalize implants in ways that reduce mechanical stress at the joint implant interface and improve bone ingrowth and implant stability; however, it is not well understood if and to what degree the AM process alters the corrosion behavior of the materials it produces. In this study, six Ti6Al4V prints manufactured via a selective laser melting (SLM) method were examined regarding their corrosion behavior in both saline and bovine calf serum (BCS) solutions. Ecorr and Icorr values were comparable between the CM-Ti6Al4V control and SLM-EDM surfaces; however, SLM surfaces were found to have more narrow passivation behavior evidenced by significant decreases in Epass values relative to CM-Ti6Al4V. We believe this is a consequence of microstructural differences between CM-Ti6Al4V and SLM-Ti6Al4V. Specifically, the SLM-Ti6Al4V demonstrated a dominant α' martensitic microstructure and decreased vanadium-rich β-phase. BCS solution had a detrimental effect on potential parameters, Ecorr and OCP, decreasing these values relative to their saline counterparts. Increased surface roughness of the SLM-printed surface seemed to amplify the effects of the BCS solution. Furthermore, modest decreases in Epass and Ipass were observed in BCS solution, suggesting that the presence of protein may also interfere with passivation behavior. These findings have implications for how SLM-Ti6Al4V implants will perform in vivo and could possibly influence implant longevity and performance.

Ultrasound-mediated rapamycin delivery for promoting osseointegration of 3D printed prosthetic interfaces via autophagy regulation in osteoporosis

Osteoporosis-derived bone marrow mesenchymal stem cells (OP-BMSCs) have impaired cell function, low osteogenic activity, and potential osteoclast inducibility, resulting in insufficient osseointegration and increased risk of catastrophic postoperative complications after arthroplasty. The low autophagy activity of OP-BMSCs contributed to poor osseointegration, which could be regulated by the classical autophagic activator, rapamycin. Hence, it is of great significance to regulate autophagy by rapamycin to promote osseointegration at the three-dimensional (3D) printed prosthetic interfaces under osteoporotic environment. In this study, 3D printed porous titanium alloy prosthetic interfaces with bionic pore size and porosity were prepared and implanted into the distal femur of osteoporosis rabbits. Subsequently, a transdermal drug delivery device was used to deliver rapamycin to the interfaces implantation sites. Ultrasound-mediated rapamycin delivery could restore the declined cellular activities (including cell viability, proliferation, migration, and osteogenesis), as well as inhibit potential osteoclast-inducing capacity and adipogenic differentiation by upregulating the autophagy level of OP-BMSCs. Moreover, percutaneous ultrasound-mediated rapamycin delivery significantly improved bone ingrowth and osseointegration of prosthetic interfaces in osteoporotic environment. To conclude, this novel therapy combining 3D printed bionic prosthesis and percutaneous ultrasound-mediated rapamycin delivery can effectively promote prosthetic interfaces osseointegration by regulating autophagy after arthroplasty for patients with osteoporosis.

Pull-Out Capability of a 3D Printed Threadless Suture Anchor with Rectangular Cross-Section: A Biomechanical Study

Suture anchor fixation is a common method for securing bone and soft tissue in the body, with proven applications in the hip, elbow, hand, knee and foot. A critical limiting factor of suture anchors is the pull-out strength, particularly in suboptimal bone. This study introduces a novel 3D printed threadless suture anchor with a rectangular cross-section. The titanium anchor was designed with surface fenestration and a porous central core to improve bone ingrowth. The aim of this study was to compare the pull-out properties of the novel threadless anchor with a traditional circular threaded suture anchor. The anchors were inserted into a 0.24 g/cm3 synthetic cancellous bone block at angles of 90° and 135° to the surface. The sutures were pulled at 180° (parallel) to the surface under a static pull test (anchor pullout) and cyclic load test using a tensile testing machine. Under the static load, the greatest pullout strength was seen with the novel threadless anchor inserted at 90° (mean, 105.6 N; standard deviation [SD], 3.5 N). The weakest pullout strength was seen with the threaded anchor inserted at 90° (mean, 87.9 N; SD, 4.1 N). In the cyclic load test, all six of the threaded anchors with a 90° insertion angle pulled out after 18 cycles (70 N). All of the threadless anchors inserted at 90° survived the cyclic test (90 N). In conclusion, the novel threadless suture anchor with rectangular cross-section and traditional threaded suture anchor had similar pullout survivorship when inserted at either 90° or 135°. In addition, the 3D printed threadless anchor has the potential for good bone integration to improve long-term stabilization.

Incorporation of Bone Morphogenetic Protein-2 and Osteoprotegerin in 3D-Printed Ti6Al4V Scaffolds Enhances Osseointegration Under Osteoporotic Conditions.

Osteoporosis is an age-related metabolic disease that results in limited bone regeneration capacity and excessive osteoclast activity. After arthroplasty in patients with osteoporosis, poor interface osseointegration resulting from insufficient bone regeneration ability often leads to catastrophic complications such as prosthesis displacement and loosening and periprosthetic fractures. In this study, we prepared a thermosensitive hydrogel loaded with bone morphogenetic protein-2 (BMP-2) to promote osteogenesis and osteoprotegerin (OPG) to inhibit excessive osteoclast activity. To construct three-dimensional (3D)-printed composite scaffolds for implantation, a hydrogel loaded with drugs was injected into porous Ti6Al4V scaffolds. The 3D-printed composite scaffolds showed good biocompatibility and sustained release of BMP-2 and OPG for more than 20 days. In vitro experiments indicated that composite scaffolds promoted osteogenic differentiation and reduced the osteoclastic activation simultaneously. Remarkably, immunofluorescence staining, micro-CT, histological, and biomechanical tests demonstrated that the sustained release of both BMP-2 and OPG from composite scaffolds significantly improved bone ingrowth and osseointegration in osteoporotic defects. In conclusion, this study demonstrated that the BMP-2- and OPG-loaded 3D-printed composite scaffolds can potentially promote osseointegration for osteoporotic patients after joint replacement.

Redefining architectural effects in 3D printed scaffolds through rational design for optimal bone tissue regeneration

Internal architecture of tissue scaffolds plays a significant role in their ability to heal critical-size bone defects. Many studies have investigated these effects but lack isolating architectural features in 3D space, hindering optimization of pore shape to improve bone ingrowth and consequently clinical outcome. To address this challenge, we developed a systematic design strategy and a high-fidelity and -precision ceramic printing technique using a stereolithography desktop printer. We used these techniques to print 5 scaffold architectures with different surface convexities/concavities, pore interconnectivities, and permeabilities, while maintaining the same porosity, average pore size, and surface area. We determined the mechanical effects of the architecture using mechanical tests with in-situ imaging, finite element, and computational fluid dynamic simulations. The effects of architecture on bioactivity and bone ingrowth were determined in a rabbit calvarial critical-size defect model at 12-week implantation, using µ-computed tomography, and histology. The results showed that bone ingrowth is significantly affected by pore interconnectivity in 3D space and maximum fluid permeability in 3D regardless of flow direction, but not permeability in one or few directions. Surface convexity/concavity did not affect bone formation in our 3D scaffolds. Bone ingrowth in scaffolds with highly interconnected pores resulted in a significantly tougher and stronger bioceramic/bone composites, compared to the inherently brittle scaffolds pre-implantation. Our findings provide a rational design of 3D scaffolds architectures for effective translation to the clinic and could be used to predict the tissue regeneration capacity of scaffolds with other architectures or made of other materials.

Novel design of additive manufactured hollow porous implants

ObjectiveOur aim is to examine the mechanical properties of two types of additive manufactured hollow porous dental implants and 6 and 12-week bone ingrowth after insertion in animals. A 3D numerical model is also developed to show detailed tissue differentiation and to provide design guidelines for implants. MethodsThe two porous and a commercial dental implant were studied by series of in vitro mechanical tests (three-point bending, torsional, screwing torque, and sawbone pull-out tests). They also evaluated by in vivo animal tests (micro-CT analysis) and ex vivo pull-out tests. Moreover, the mechano-regulation algorithm was implemented by the 3D finite element model to predict the history of tissue differentiation around the implants. ResultsThe results showed that the two porous implants can significantly improve osseointegration after 12-week bone healing. This resulted in good fixation and stability of implants, giving very high maximum pull-out strength 413.1 N and 493.2 N, compared to 245.7 N for the commercial implant. Also, several features were accurately predicted by the mechano-regulation model, such as transversely connected bone formation, and bone resorption occurred in the middle of implants. SignificanceSystematic studies on dental implants with multiple approaches, including new design, mechanical tests, animal tests, and numerical modeling, were performed. Two hollow porous implants significantly improved bone ingrowth compared with commercial implants, while maintaining mechanical strength. Also, the numerical model was verified by animal tests. It improved the efficiency of design and reduce the demand for animal sacrifice.

Bioinspired mineral hydrogels as nanocomposite scaffolds for the promotion of osteogenic marker expression and the induction of bone regeneration in osteoporosis

Osteoporosis is one of the most prevalent age-related diseases worldwide and is characterized by a systemic deterioration of bone strength (bone mineral density and bone quality) with a resulting increase in fragility fractures. Due to the complex osteoporotic pathological environment, it is a huge challenge to induce bone regeneration under osteoporosis conditions. In this study, we successfully nanoengineer a bioinspired mineralized hydrogel from the supramolecular assembly of nano-hydroxyapatite, sodium carbonate, and polyacrylic acid, termed as CHAp-PAA. The resultant nanocomposite hydrogels can maintain their initial morphology and mechanical properties under physiological conditions, while exhibiting good primary stability, biocompatibility, bioactivity, and osteoconductivity. We demonstrate that this optimized hydrogel scaffold has shown superior performance for bone marrow stem cells (BMSCs) proliferation, differentiation, and extracellular matrix production in vitro. Remarkably, the mineralized CHAp-PAA hydrogels could be used as scaffolds for the critical-sized bone defect (6.0 mm diameter and 10.0 mm depth) in the osteoporotic rabbit model. Without the delivery of additional therapeutic agents or stem cells, these CHAp-PAA hydrogel scaffolds can improve bone ingrowth and accelerate new bone formation even in complex osteoporotic pathological environments. Therefore, this work presents a type of bioinspired multifunctional mineral hydrogel that offers an alternative strategy to manage osteoporosis. Statement of Significance•We successfully nanoengineer a bioinspired mineralized hydrogel from supramolecular assembly of nano-hydroxyapatite, sodium carbonate, and polyacrylic acid, termed as CHAp-PAA. The resultant nanocomposite hydrogels can maintain their initial morphology and mechanical properties under physiological conditions, while exhibiting good primary stability, biocompatibility, bioactivity, and osteoconductivity.•We demonstrate that this optimized hydrogel scaffold has shown superior performance for bone marrow stem cells (BMSCs) proliferation, differentiation, and extracellular matrix production in vitro.•Remarkably, the mineralized CHAp-PAA hydrogels could be used as scaffold for the critical-sized bone defect (6.0 mm diameter and 10.0 mm depth) in osteoporotic rabbit model. Without delivery of additional therapeutic agents or stem cells, these CHAp-PAA hydrogel scaffolds can improve bone ingrowth and accelerate new bone formation even in complex osteoporotic pathological environment.

Osteoclast and osteoblast response to strontium-doped struvite coatings on titanium for improved bone integration.

To develop implants with improved bone ingrowth, titanium substrates were coated with homogeneous and dense struvite (MgNH4PO4·6H2O) layers by means of electrochemically assisted deposition. Strontium nitrate was added to the coating electrolyte in various concentrations, in order to fabricate Sr-doped struvite coatings with Sr loading ranging from 10.6 to 115μg/cm2. It was expected and observed that osteoclast activity surrounding the implant was inhibited. The cytocompatibility of the coatings and the effect of Sr-ions in different concentrations on osteoclast formation were analyzed in vitro. Osteoclast differentiation was elucidated on morphological, biochemical as well as on gene expression level. It could be shown that moderate concentrations of Sr2+ had an inhibitory effect on osteoclast formation, while the growth of osteoblastic cells was not negatively influenced compared to pure struvite surfaces. In summary, the electrochemically deposited Sr-doped struvite coatings are a promising approach to improve bone implant ingrowth.

Three-Dimensional Printed Porous Titanium Screw with Bioactive Surface Modification for Bone–Tendon Healing: A Rabbit Animal Model

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.

Effect of bone sialoprotein coating on progression of bone formation in a femoral defect model in rats.

In orthopedic and trauma surgery, calcium phosphate cement (CPC) scaffolds are widely used as substitute for autologous bone grafts. The purpose of this study was to evaluate bone formation in a femoral condyle defect model in rats after scaffold-coating with bioactive bone sialoprotein (BSP). Our hypothesis was that BSP-coating results in additional bone formation. In 20 Wistar rats, defects of 3.0mm diameter were drilled into the lateral femoral condyles of both legs. BSP-coated scaffolds or uncoated control scaffolds were implanted into the defects. After 4 and 8 weeks, five rats of each group were euthanized, respectively. µCT scans and histological analyses were performed. The ratio of bone volume-total volume (BV/TV) was analyzed and histological sections were evaluated. At week four, bone fraction reached 5.2 ± 1.7% in BSP-coated scaffolds and 4.5 ± 3.2% in the control (p = 0.06). While bone fraction of the BSP-group did not change much between week four and eight [week eight: 5.4 ± 3.8% (p = 0.53)], there was a tendency towards an increase in the control [week eight: 7.0 ± 2.2% (p = 0.08)]. No significant difference in bone fraction were observable between BSP-coated and uncoated scaffolds at week eight (p = 0.08). A significant superiority of BSP-coated scaffolds over uncoated scaffolds could not be proven. However, BSP-coating showed a tendency towards improving bone ingrowth in the scaffolds 4 weeks after implantation. This effect was only short-lived: bone growth in the control scaffolds tended to outpace that of the BSP-group at week eight.

The Influence of Microstructure on the Surface Charge of Sintered Hydroxyapatite Ceramics

Hydroxyapatite (HAp) has shown the ability to store a charge induced by electrical polarization a method potential for improved bone ingrowth. In this work electrical polarization was carried out on HAp ceramics with three different microstructures, obtained at three different sintering temperatures. Microstructure of the sintered HAp was evaluated from density measurements and SEM observations. Sintered HAp tablets were electrically polarized in an electric field of 5 kV/cm at 400 °C for 1h. Surface charges investigated by thermally stimulated depolarization current measurements showed 104,8 μC/cm2 for denser tablets, while charge density of 22,8 μC/cm2 was obtained for less dense tablets.

Improved bone ingrowth of tricalcium phosphate filled Poly(methyl methacrylate) (PMMA) bone cements in vivo

The cement augmentation technique using poly(methyl methacrylate) (PMMA) is considered to be the most effective method for fixation of osteoporotic fracture because of its outstanding mechanical properties. However, the low bio-degradation of PMMA, which hinders bone ingrowth, limits it potential for a broad range of applications. Previous studies have shown blending β-tricalcium phosphate (β-TCP) with PMMA was able to improve the osteoconduction while the material still suffered poor mechanical properties due to the poor compatibility between two components. In this study, we explored the use of hydroxyethyl methacrylate (HEMA) as a compatibilizer for improving the affinity of TCP/PMMA blends system. The resultant TCP/HEMA/PMMA(THP) composite cements exhibited similar setting properties to PMMA cement but much better mechanical properties than composite systems without HEMA as a compatibilizer. No cytotoxicity or hemolysis was observed in the THP bone cement system by biochemical assays. Bone ingrowth was significantly improved at 12 weeks. The reinforced pull-out strength of screws was observed at 4, 8, 12 weeks through in vivo studies performed on rabbit femurs. The THP system, as an injectable bone cement material, shows great potential for use in the cement augmentation technique.

Novel adaptive finite element algorithms to predict bone ingrowth in additive manufactured porous implants

Bone loss caused by stress shielding of metallic implants is a concern, as it can potentially lead to long-term implant failure. Surface coating and reducing structural stiffness of implants are two ways to improve bone ingrowth and osteointegration. Additive manufacturing, through selective laser sintering (SLS) or electron beam melting (EBM) of metallic alloys, can produce porous implants with bone ingrowth regions that enhance osteointegration and improve clinical outcomes. Histology of porous Ti6Al4V plugs of two pore sizes with and without electrochemically deposited hydroxyapatite coating, implanted in ovine condyles, showed that bone formation did not penetrate deep into the porous structure, whilst significantly increased bone growth along coated pore surfaces (osteointegration) was observed. Finite Element simulations, combining new algorithms to model bone ingrowth and the effect of surface modification on osteoconduction, were verified with the histology results. The results showed stress shielding of porous implants made from conventional titanium alloy due to material stiffness and implant geometry, limiting ingrowth and osteointegration. Simulations for reduced implant material stiffness predicted increased bone ingrowth. For low modulus Titanium-tantalum alloy (Ti-70%Ta), reduced stress shielding and enhanced bone ingrowth into the porous implant was found, leading to improved mechanical interlock. Algorithms predicted osteoconductive coating to promote both osteointegration and bone ingrowth into the inner pores when they were coated. These new Finite Element algorithms show that using implant materials with lower elastic modulus, osteoconductive coatings or improved implant design could lead to increased bone remodelling that optimises tissue regeneration, fulfilling the potential of enhanced porosity and complex implant designs made possible by additive layer manufacturing techniques.

In vitro and in vivo investigation of PLA/PCL scaffold coated with metformin-loaded gelatin nanocarriers in regeneration of critical-sized bone defects

Large bone defects constitute a major challenge in bone tissue engineering and usually fail to heal due to the incomplete differentiation of recruited mesenchymal stem cells (MSCs) into osteogenic precursor cells. As previously proposed, metformin (MET) induces differentiation of MSCs into osteoblastic lineages in vitro. We fabricated a Poly (lactic acid) and Polycaprolactone (PLA/PCL) scaffold to deliver metformin loaded gelatin nanocarriers (MET/GNs) to critical-sized calvarial bone defects in a rat model. The scaffolds were evaluated regarding their morphology, porosity, contact angle, degradation rate, blood compatibility, biomechanical, cell viability and their osteogenic differentiation. In animal study, the defects were filled with autograft, scaffolds and a group was left empty. qRT-PCR analyses showed the expression level of osteogenic and angiogenic markers considerably increased in MET/GNs-PLA/PCL. The in vivo results showed that MET/GNs-PLA/PCL improved bone ingrowth, angiogenesis and defect reconstruction. Our results represent the applicability of MET/GNs-PLA/PCL for successful bone regeneration.

The effect of hydroxyapatite on bone ingrowth into porous-coated titanium implants.

Two different groups of hydroxyapatite (HA) coated and uncoated porous titanium implants, 250-350 m and 500-700 m diameter beads, were press-fit in femoral canine cancellous bone. After 12 weeks, the dogs were euthanized and histomorphometric backscattered electron microscopy studies were carried out. Comparing HA-coated versus uncoated implants in the 250-350 m bead diameter group percentage of bone (P=0.01) and bone index (P=0.01), were higher in the HA-coated implants. Comparing HA-coated versus uncoated implants in the 500-700 m bead diameter group bone ingrowth (P=0.01) and bone depth penetration (P=0.008), were higher in HA-coated samples. It can be concluded that the HA coating was an effective method to improve bone formation and ingrowth in the porous implants. (Hip International 2002; 2: 153-7).