Bone Ingrowth Research Articles

Mechanical Behaviour of Additive Manufactured PEEK/HA Porous Structure for Orthopaedic Implants: Materials, Structures and Manufacturing Processes

Polyether-ether-ketone (PEEK) composites represent one of the most promising approaches to overcoming the weak osseointegration associated with the bioinertness of PEEK, making them highly suitable for clinical translation. Implants with porous structures fabricated by additive manufacturing offer the potential for long-term stability by promoting bone ingrowth. However, despite the importance of porous design, there is still no consensus on the optimal approach for PEEK-based composites. Given the significance of permeability and mechanical properties as functional indicators closely linked to osseointegration, the effects of material composition, structural design, and manufacturing processes on the permeability and mechanical properties of PEEK/hydroxyapatite (HA) scaffolds were systematically investigated in this study. In terms of permeability, the axial permeability of scaffolds with different pore sizes and representative volume elements varied within the range of 0.3-24.8 × 10-9 m2. Among scaffolds with similar relative density, the Gyroid structure exhibited the lowest permeability, while the orthogonal structure demonstrated the highest. For cylindrical scaffolds, circumferential permeability decreased with increasing penetration depth, suggesting a potential reduction in bone ingrowth speed with depth. As for mechanical properties, the experimentally determined effective elastic modulus and effective yield strength of the scaffolds ranged from 675.1 MPa to 65.2 MPa and 43.5 MPa to 4.1 MPa, respectively. The permeability and mechanical properties of PEEK/HA scaffolds with relative density ranging from 35-50% aligned with the those of human cancellous bone. By applying heat treatment at 240°C for 120 minutes, the crystallinity of PEEK increased to 37.2%, resulting in a substantial improvement in both the strength and stiffness of the scaffolds. However, excessive crystallinity led to brittle fracture, which in turn reduced the strength of the scaffolds. This study employed a systematic research approach to investigate how material composition, structural design, and manufacturing processes influence the mechanical properties and permeability of PEEK composite bone scaffolds, which are crucial for bone ingrowth. The results offered insights that support the design, manufacturing, and performance evaluation of PEEK-based porous implants.

HUVECs’ Expressway Based on Magnesium Ion Doped Hierarchical Scaffold for Rapid Angiogenesis and Bone Ingrowth

AbstractDelayed union or nonunion remains an extremely challenging predicament even after the application of currently available engineering scaffolds for the treatment of critical‐sized bone defects. The angiogenesis throughout the artificial bone repair scaffold to achieve “angiogenic‐osteogenic coupling” is regarded as an effective approach to solving this issue. The newly formed blood vessels can accelerate the supply of oxygen and nutrients, thereby triggering subsequent bone regeneration. Therefore, scaffolds featuring an angiogenic microenvironment that promotes cell adhesion and migration should be designed for superior bone repair. Herein, a magnesium ion‐doped hierarchical scaffold is fabricated using a polymer blend system of chitosan/polyethyleneimine with inherent micro‐phase separation and complexation. Due to the microscopic sea‐island structure and the stable doped magnesium ions, the cell adhesion behavior underwent a significant transformation. Meanwhile, the pathways related to cell adhesion, migration, and angiogenesis are activated, and the critical target thrombospondin 1 is upregulated. Consequently, the cell adhesion capacity is augmented, 6 times the cell migration rate is attained, and the angiogenesis of human umbilical vein endothelial cells is significantly expedited. Eventually, rapid bone ingrowth and satisfactory bone defect repair are approximated in vivo, making the composite scaffold a promising clinical candidate for bone engineering.

Impact of Surgical Alignment, Bone Properties, Anterior-Posterior Translation, and Implant Design Factors on Fixation in Cementless Unicompartmental Knee Arthroplasty.

Micromotion exceeding 150 μm at the implant-bone interface may prevent bone formation and limit fixation after cementless knee arthroplasty. Understanding the critical parameters impacting micromotion is required for optimal implant design and clinical performance. However, few studies have focused on unicompartmental knee arthroplasty (UKA). This study assessed the impacts of alignment, surgical, and design factors on implant-bone micromotions for a novel cementless UKA design during a series of simulated daily activities. Three finite element models that were validated for predicting micromotion of cementless total knee arthroplasty (TKA) were loaded with design-specific kinematics/loading to simulate gait (GT), deep knee bending (DKB), and stair descent (SD). The implant-bone micromotion and the porous surface area ideal for bone ingrowth were estimated and compared to quantify the impact of each factor. Overall, the peak tray-bone micromotions were consistently found at the lateral aspect of the tibial baseplate and were consistently higher than the femoral micromotions. The femoral micromotion was insensitive to almost all the factors studied, and the porous area favorable for bone ingrowth was no less than 93%. For a medial uni, implanting the tray 1 mm medially or the femoral component 1 mm laterally reduced the tibial micromotion by 19.3% and 26.3%, respectively. Differences in tray-bone micromotion due to bone moduli were up to 59.8%. A 5 mm more posterior femoral translation increased the tray-bone micromotion by 35.8%. The presence of the tray keel prevented the spread of the micromotion and increased the overall porous surface area, but also increased peak micromotion. The tray peg and the femoral anterior peg had little impact on the micromotion of their respective implants. In conclusion, centralizing the load transfer to minimize tibial tray applied moment and optimizing the fixation features to minimize micromotion are consistent themes for improving cementless fixation in UKA. Perturbation of femoral-bone alignment may be preferred as it would not create under/overhang on the tibia.

Nickel–titanium alloy porous scaffolds based on a dominant cellular structure manufactured by laser powder bed fusion have satisfactory osteogenic efficacy

Nickel–titanium (NiTi) alloy is a widely utilized medical shape memory alloy (SMA) known for its excellent shape memory effect and superelasticity. Here, laser powder bed fusion (LPBF) technology was employed to fabricate a porous NiTi alloy scaffold featuring a topologically optimized dominant cellular structure that demonstrates favorable physical and superior biological properties. Utilizing a porous structure topology optimization method informed by the stress state of human bones, two types of cellular structures—compression and torsion—were designed, and porous scaffolds were produced via LPBF. The physical properties of the porous NiTi alloy scaffolds were evaluated to confirm their biocompatibility, while their osteogenic efficacy was investigated through both in vivo and in vitro experiments, with comparisons made against a traditional octahedral unit cell structure. NiTi alloy porous scaffolds can be nearly net-shaped via LPBF and exhibit favorable physical properties, including a low elastic modulus, high hydrophilicity, a specific linear expansion rate, as well as superelastic and shape memory effects. These scaffolds demonstrate excellent biocompatibility, support in vitro osteogenesis, and possess significant in vivo bone ingrowth capabilities. When compared to titanium alloys, NiTi alloys show comparable osteogenic properties in vitro but superior bone ingrowth properties in vivo. Additionally, among octahedral-type, torsion-type, and topologically optimized compression-type porous scaffolds, the latter demonstrates enhanced bone ingrowth properties. LPBF technology is effective for manufacturing porous NiTi alloy scaffolds with fine pore structures and excellent mechanical properties. The scaffolds based on topologically optimized dominant cellular structures facilitate satisfactory and efficient bone formation.

Composite Scaffold Materials of Nanocerium Oxide Doped with Allograft Bone: Dual Optimization Based on Anti-Inflammatory Properties and Promotion of Osteogenic Mineralization.

Spinal fusion technique is widely used in the treatment of lumbar degeneration, cervical instability, disc injury, and spinal deformity. However, it is usually accompanied by a high incidence of fusion failure and pseudoarthrosis, placing higher demands on bone implants. Therefore, materials with good biocompatibility, osteoconductivity, and even induce bone ingrowth, which can be used to improve spinal fusion rate and bone regeneration, have become a hot research topic. Here, ultra-small cerium oxide nanoparticles (CeO2 NPs) are prepared and loaded onto the surface of the homograft bone surface to prepare a composite scaffold AB@PLGA/CeO2. The composite scaffold shows the competitive ability to promote osteoblast differentiation in vitro. In vivo experiments show that AB@PLGA/CeO2 has a good bone enhancement effect. In particular, good biological effects of collagen fiber formation, osteogenic mineralization, and tissue repair are shown in intervertebral implant fusion. Further, transcriptome sequencing confirms that CeO2 NPs promote osteogenic differentiation and mineralization by regulating extracellular matrix (ECM) and collagen formation. Meanwhile, CeO2 NPs can regulate the function of the PI3K-Akt signaling pathway to exert its ability to promote osteogenic differentiation and mineralization and affect p53 and cell cycle signaling pathway to regulate osteogenic differentiation and mineralization. Hence, the proposed scaffold is a promising strategy for intervertebral fusion in the clinic.

Iron Chelators Augment Large Osteochondral Allograft Osseointegration in a Preclinical Canine Model.

Osteochondral allograft transplantation (OCAT) can be a successful joint restoration treatment option for large post-traumatic articular defects but is still associated with significant revision and failure rates. Despite recent advances that have improved OCAT success, insufficient osteochondral allograft (OCA) osseointegration remains a major cause of failure. Deferoxamine (DFO) is an effective angiogenic and osteo-anabolic iron chelator that consistently promotes bone neovascularization and regeneration. This study was designed to investigate local delivery of DFO for augmenting OCA osseointegration using a preclinical canine model for OCAT in the knee and hip as commonly affected joints. On Institutional Animal Care and Use Committee (IACUC) approval, 12 purpose-bred dogs underwent OCAT of the femoral head or femoral condyles with DFO or DFO-free (controls) microspheres in recipient sites. OCA revascularization, cellular repopulation, and integration were evaluated based on functional, diagnostic imaging, microcomputed tomography, histology, and immunohistochemistry outcome measures. Local delivery of DFO into OCAT recipient sites was associated with maintained or improved joint function, superior radiographic appearance, significantly greater trabecular thickness, higher bone volume, and new bone ingrowth compared with DFO-free controls. OCA osseointegration is dependent on cellular repopulation and neovascularization, resulting in new bone ingrowth through creeping substitution, and insufficient osseointegration with resorption and subsidence of the OCA remains a major cause of failure after transplantation. The results of this study suggest that local delivery of DFO using a controlled microsphere release system may reduce resorption and improve revascularization and cellular repopulation to increase new bone ingrowth, potentially expediting OCA osseointegration after transplantation.

Clinical and Radiographic Outcomes of a Long Cementless Monobloc Stem for Revision Total Hip Arthroplasty Due to Chronic Periprosthetic Infection

BackgroundA long cementless monobloc stem is widely used for aseptic loosening, with satisfactory five-to-ten-year outcomes reported. Nonetheless, related studies on chronic periprosthetic joint infection (PJI) are scant. This study evaluated the clinical and radiographic outcomes of the stem in two-stage revisions due to PJI. MethodsThis prospective multicenter cohort study consisted of patients from three medical centers who were enrolled in a single arm from January 2017 to May 2022. All patients were diagnosed with chronic PJI based on International Consensus Meeting (ICM) criteria and underwent two-stage revisions using a long monobloc cementless revision stem. Among 44 patients, 37 (12 women and 25 men) completed an average follow-up of 35.6 months (range, 14 to 75). The primary outcome was the stability of the stem; secondary outcomes included infection eradication, Harris hip score, leg length discrepancy, major complications, and isolated pathogens at intraoperative cultures. ResultsAt one year after revision, the infection-free prosthesis survival rate was 97.3% (95% CI [confidence interval]: 96.4 to 98.2%). At the last follow-up, the mean subsidence was 2.9 ± 2.1 mm (range, 0.8 to 4.8). Postoperative leg length discrepancy averaged −4.6 ± 4.9 mm (range, −16 to 0). The Engh score averaged 14.1 ± 6.9 (range, 0 to 22). The Harris hip score improved from a preoperative average of 35.7 ± 8.5 (range, 12 to 50) to 80.4 ± 9.3 (range, 58 to 92) at the 1-year postoperative follow-up (P < 0.01). ConclusionThe long cementless monobloc stem used in the current study presents a feasible option for two-stage revision in cases of chronic PJI. The bone ingrowth and stability could be observed within the short follow-up time.

Structural design and biomechanical analysis of a combined titanium and polyetheretherketone cage based on PE-PLIF fusion.

In lumbar spinal fusion, the titanium cage tends to cause stress shielding due to their high elastic modulus, which can lead to degenerative lesions in adjacent spinal segments. Furthermore, polyetheretherketone (PEEK) cages have certain material characteristics that do not promote bone ingrowth and fusion stability. In this study, a new cage was designed, and its biomechanical performance in percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) was analyzed using the finite element (FE) method. A complete model of the L4-L5 lumbar spine was established, and static and harmonic vibration FE analysis models were developed based on it. The biomechanical properties of titanium, PEEK, and combined cage in PE-PLIF fusion were compared. The strain capacity of the combined fusion increased by 9.5% when compared to the titanium fusion. The surgical model under the combined fusion reduces the L5 endplate stress by 12% in the forward flexion condition and the fusion stress by 17% in the vibration condition compared to the model supported by the titanium fusion, and the differences in screw stress and mobility among the three models are not significant in multiple conditions. Consequently, the combined cage demonstrates a certain reduction in the stress-shielding effect when compared to the titanium cage; it has better fusion effect and provides theoretical support and guidance for the design of the clinical fusion cage.

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.

Bone ingrowth in randomly distributed porous interbody cage during lumbar spinal fusion

Porous interbody cages are often used in spinal fusion surgery since they allow bone ingrowth which facilitates long-term stability. However, the extent of bone ingrowth in and around porous interbody cages has scarcely been investigated. Moreover, tissue differentiation might not be similar around the superior and inferior cage-bone interfaces. Using mechanobiology-based numerical framework and physiologic loading conditions, the study investigates the spatial distribution of evolutionary bone ingrowth within randomly distributed porous interbody cages, having varied porosities. Finite Element (FE) microscale models, corresponding to cage porosities of 60 %, 72 %, and 83 %, were developed for the superior and inferior interfacial regions of the cage, along with the macroscale model of the implanted lumbar spine. The implant-bone relative displacements of different porosity models were mapped from macroscale to microscale model. Bone formation of 10–40 % was predicted across the porous cage models, resulting in an average Young's modulus ranging between 765 MPa and 915 MPa. Maximum bone ingrowth of ∼34 % was observed for the 83 % porous cage, which was subject to low implant-bone relative displacements (maximum 50μm). New bone formation was found to be greater at the superior interface (∼34 %) as compared to the inferior interface (∼30 %) for P83 model. Relatively greater volume of fibrous tissue was formed at the implant-bone interface for the cage with 60 % and 72 % porosities, which might lead to cage migration and eventual failure of the implant. Hence, the interbody cage with 83 % porosity appears to be most favorable for bone ingrowth, provided sufficient mechanical strength is offered.

Biocompatibility and Bone Regeneration by Shape Memory Polymer Scaffolds.

Biodegradable, shape memory polymer (SMP) scaffolds based on poly(ε-caprolactone) (PCL) offer unique advantages as a regenerative treatment strategy for critical-sized bone defects. In particular, a conformal fit may be achieved following exposure to warm saline, thereby improving osseointegration and regeneration. Advancing the clinical translation of these SMP scaffolds requires establishment of efficacy not only in non-loading models, but also load-bearing or load-sharing models. Thus, the present study evaluated the biocompatibility and bone regeneration potential of SMP scaffolds in a rabbit distal femoral condyle model. Two distinct SMP scaffold compositions were evaluated, a "PCL-only" scaffold formed from PCL-diacrylate (PCL-DA) and a semi-interpenetrating network (semi-IPN) formed from PCL-DA and poly(L-lactic acid) (PCL:PLLA). Semi-IPN PCL:PLLA scaffolds possess greater rigidity and faster rates of degradation versus PCL scaffolds. In vivo biocompatibility was assessed with a rat subcutaneous implantation model, whereas osseointegration was assessed with a 4 mm × 8 mm rabbit distal femoral condyle defect model. Both types of SMP scaffolds exhibited excellent biocompatibility marked by infiltration with fibrous tissue and a minimal inflammatory response. When implanted in the rabbit distal femur, both SMP scaffolds supported bone ingrowth. Collectively, these results demonstrate that the SMP scaffolds are biocompatible and integrate with adjacent host osseous tissues when implanted in vivo in a load-sharing environment. This study provides key proof-of-concept data necessary to proceed with large animal translational studies and clinical trials in human subjects.

Radiological evaluation of fusion patterns after Lateral Lumbar Interbody fusion with 3D-printed porous titanium cages vs. conventional titanium cages.

The assessment of segmental fusion after Lateral Lumbar Interbody fusion (LLIF) using 3D-printed porous titanium cage is still not well studied. Various criteria, such as the presence of bone bridges (BB) between adjacent vertebrae, serve as indicators for anterior fusion. However, limited radiological studies have investigated zygapophyseal joints (ZJ) status following LLIF with porous titanium cages vs. conventional titanium threaded cages. The porous design of the latest titanium intervertebral cages is thought to enhance the bone-to-implant fusion rate. This radiological study aimed to compare the fusion patterns post-LLIF using 3D-printed porous titanium cages against those using threaded titanium cages. This radiological study aimed to compare the fusion patterns after LLIF using 3D-printed porous titanium cages against those using threaded titanium cages. This retrospective, single-center radiological study involved 135 patients who underwent LLIF and posterior percutaneous screw fixation for degenerative spondylolisthesis. The study included 51 patients (Group A) with the novel porous titanium cages and 84 patients (Group B) with conventional threaded titanium cages. Inclusion criteria mandated complete radiological data and a minimum follow-up period of 24 months. The study evaluated intervertebral bone bridges (BB) for anterior fusion and zygapophyseal joints (ZJ) ankylotic degeneration, based on Pathria et al., as evidence of posterior fusion and segmental immobilization. Two years after surgery, intervertebral BB were identified in 83 segments (94.31%) in Group A and in 87 segments (88.77%) in Group B. ZJ Pathria grade I was observed in 2 segments (2.27%) of Group A and in 4 segments (4.08%) of Group B. Grade II was seen in 5 segments (5.68%) of Group A and in 6 segments (6.12%) of Group B. Posterior fusion, classified as grade III, was found in 81 segments (92.04%) of Group A and 88 segments (89.79%) of Group B. Subsidence incidence was 5.88% (3 segments) for the novel cage and 9.88% (8 segments) for the conventional cage. The architecture of porous titanium cages offers a promising solution for increasing bone ingrowth and bridging space, supporting successful spinal fusion while minimizing the risk of subsidence.

Laser powder bed fusion printed poly-ether-ether-ketone/bioactive glass composite scaffolds with dual-scale pores for enhanced osseointegration and bone ingrowth

Although poly-ether-ether-ketone (PEEK) implants hold significant medical promise, their bioinert nature presents challenges in osseointegration and bone ingrowth within clinical contexts. To mitigate these challenges, the present study introduces Diamond PEEK/bioactive glass (BG) composite scaffolds, characterized by macro/micro dual-porous structures, precisely fabricated via laser powder bed fusion (LPBF) technology. The findings indicate that an increase in BG content within these scaffolds significantly augments their hydrophilicity and hydroxyapatite formation capacities. Stress-strain curve analysis demonstrates reliable load-bearing stability across all scaffold types. In vitro assessments confirmed the non-cytotoxicity of PEEK/BG samples and demonstrated improved osteogenic differentiation and mineralization with increased BG incorporation. Further, in vivo experiments illustrated that the Diamond porous structure of these scaffolds facilitated bone growth, an effect notably amplified with higher BG content. Particularly in groups with 15 wt.% and 25 wt.% BG scaffolds, new bone formation was observed not only within the macropores of the Diamond structure but also within the micropores inside the scaffold rod, suggesting an almost seamless fusion with the new bone. This demonstrates the scaffolds’ effective osteointegration and bone ingrowth properties. This study conclusively established the effectiveness of Diamond-structured PEEK/BG composite scaffolds, fabricated via LPBF, in bone repair. It highlights the crucial role of BG in enhancing osteogenic potential through interaction with the macro/micro pores of the scaffold. Statement of significanceThis study addresses the bioinert nature of PEEK implants by developing Diamond-structured PEEK/bioactive glass (BG) composite scaffolds by laser powder bed fusion. The dual-porous macro/microstructure enhances hydrophilicity and hydroxyapatite formation, vital for bone regeneration. By adjusting the BG content, we controlled the melt viscosity and sintering rate, leading to the formation of beneficial microscale pores. These pores resolve the issue of ineffective bioactive fillers in previous LPBF-fabricated scaffolds, enhancing the osteogenic potential of BG and inducing superior bone ingrowth and osseointegration. In vitro and in vivo analyses show enhanced osteogenic differentiation, mineralization, and bone growth, underscoring the clinical potential of these scaffolds for bone repair.

Prediction of bone ingrowth into a porous novel hip-stem: A finite element analysis integrated with mechanoregulatory algorithm.

Bone ingrowth into a porous implant is necessary for its long-term fixation. Although attempts have been made to quantify the peri-implant bone growth using finite element (FE) analysis integrated with mechanoregulatory algorithms, bone ingrowth into a porous cellular hip stem has scarcely been investigated. Using a three-dimensional (3D) FE model and mechanobiology-based numerical framework, the objective of this study was to predict the spatial distribution of evolutionary bone ingrowth into an uncemented novel porous hip stem proposed earlier by the authors. A CT-based FE macromodel of the implant-bone structure was developed. The bone material properties were assigned based on CT grey value. Peak musculoskeletal loading conditions, corresponding to level walking and stair climbing, were applied. The geometry of the implant-bone macromodel was divided into multiple submodels. A suitable mapping framework was used to transfer maximum nodal displacements from the FE macromodel to the cut boundaries of the FE submodels. CT grey value-based bone materials properties were assigned to the submodels. Thereafter, the submodels were solved and simulations of bone ingrowth were carried out using mechanoregulatory principle. A gradual increase in the average Young's modulus, from 1200 to 1500 MPa, of the bone tissue layer was observed considering all the submodels. The distal submodel exhibited 82% of bone ingrowth, whereas the proximal submodel experienced 65% bone ingrowth. Equilibrium in the bone ingrowth process was achieved in 7 weeks postoperatively, with a notable amount of bone ingrowth that should lead to biological fixation of the novel hip stem.

3D-Printed-Cryogel-Impregnated Functionalized Scaffold Augments Bone Regeneration in Critical Tibia Fracture in Goat.

Critical-size bone trauma injuries present a significant clinical challenge because of the limited availability of autografts. In this study, a photocurable composite comprising of polycaprolactone, polypropylene fumarate, and nano-hydroxyapatite (nHAP) (P─P─H) is printed, which shows good osteoconduction in a rat model. A cryogel composed of gelatin-nHAP (GH) is developed to incorporate osteogenic components, specifically bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA), termed as GH+B+Z, which is investigated for osteoinductive property in a rat model. Further, a 3D-printed P─P─H scaffold impregnated with GH+B+Z is designed and implanted in a critical-size defect (25×10×5mm) in goat tibia. After 4 months, the scaffold is well-integrated with adjacent native bone, with osteoinduction observed in the cryogel-filled region and osteoconduction over the printed scaffold. X-ray radiography and micro-CT analysis showed bone in-growth in the treatment group with 45 ± 1.4% bone volume/tissue volume (BV/TV), while the defect remained unhealed in the control group with BV/TV of 10.5 ± 0.5%. Histology showed significant cell infiltration and matrix deposition over the printed P─P─H scaffold and within the GH cryogel site in the treatment group. Immunohistochemical staining depicted significantly higher normalized collagen I intensity in the treatment group (34.45 ± 2.61%) compared to the control group (4.22 ± 0.78).

Evaluation of biocompatibility and osseointegration of multi-component TiAl6V4 titanium alloy implants.

This study aimed to investigate the biocompatibility and osseointegration of novel titanium (Ti) implants with a perforated part with high surface roughness (Ra >4 μm) and a smooth solid part (test group), as compared to smooth solid Ti implants (control group; Ra < 0.8 μm). Test and control implants were implanted in rabbit femurs. After 4 and 15 weeks, host tissue reaction and quality of tissue formed were evaluated with histopathology, while micro-CT scans were used to quantitatively assess bone-implant contact (BIC), surrounding bone formation, and bone ingrowth. After 4 and 15 weeks, minimal host reaction was found in the test group. Histopathological analysis showed new bone formation around the implants in both the test and control groups after 4 weeks. Furthermore, additional bone growth was often observed within the holes of the test implants. After 15 weeks, the test implants showed high bone ingrowth and the presence of mature bone in direct contact with the implant surface, whereas, bone ingrowth was poorer for the control group with 30% of the control implants, showing larger gaps at the bone-implant interface. Quantitative micro-CT analysis revealed comparable BIC and bone formation in both groups at 4 weeks, but higher BIC and more bone formation in the test group than in the control group after 15 weeks. No significant differences were observed in any of the analyses. In conclusion, partially perforated, high-roughness Ti implants showed excellent osseointegration and minimal host reaction, indicating their potential for orthopedic applications in bone repair and regeneration.

3D-ink-extruded titanium scaffolds with porous struts and bioactive supramolecular polymers for orthopedic implants

Porous titanium addresses the longstanding orthopedic challenges of aseptic loosening and stress shielding. This work expands on the evolution of porous Ti with the manufacturing of hierarchically porous, low stiffness, ductile Ti scaffolds via direct-ink write (DIW) extrusion and sintering of inks containing Ti and NaCl particles. Scaffold macrochannels were filled with a subtherapeutic dose of recombinant bone morphogenetic protein-2 (rhBMP-2) alone or co-delivered within a bioactive supramolecular polymer slurry (SPS) composed of peptide amphiphile nanofibrils and collagen, creating four treatment conditions (Ti struts: microporous vs. fully dense; BMP-2 alone or with SPS). The BMP-2-loaded scaffolds were implanted bilaterally across the L4 and L5 transverse processes in a rat posterolateral lumbar fusion model. In-vivo bone growth in these scaffolds is evaluated with synchrotron X-ray computed microtomography (µCT) to study the effects of strut microporosity and added biological signaling agents on the bone formation response. Optical and scanning electron microscopy confirms the ∼100 µm space-holder micropore size, high-curvature morphology, and pore fenestrations within the struts. Uniaxial compression testing shows that the microporous strut scaffolds have low stiffness and high ductility. A significant promotion in bone formation was observed for groups utilizing the SPS, while no significant differences were found for the scaffolds with the incorporation of micropores. Statement of significanceBy 2050, the anticipated number of people aged 60 years and older worldwide is anticipated to double to 2.1 billion. This rapid increase in the geriatric population will require a corresponding increase in orthopedic surgeries and more effective materials for longer indwelling times. Titanium alloys have been the gold standard of bone fusion and fixation, but their use has longstanding limitations in bone-implant stiffness mismatch and insufficient osseointegration. We utilize 3D-printing of titanium with NaCl space holders for large- and small-scale porosity and incorporate bioactive supramolecular polymers into the scaffolds to increase bone growth. This work finds no significant change in bone ingrowth via space-holder-induced microporosity but significant increases in bone ingrowth via the bioactive supramolecular polymers in a rat posterolateral fusion model.

In Vivo Assessment of a Triple Periodic Minimal Surface Based Biomimmetic Gyroid as an Implant Material in a Rabbit Tibia Model.

Biomimetic approaches to implant construction are a rising frontier in implantology. Triple Periodic Minimal Surface (TPMS)-based additively manufactured gyroid structures offer a mean curvature of zero, rendering this structure an ideal porous architecture. Previous studies have demonstrated the ability of these structures to effectively mimic the mechanical cues required for optimal implant construction. The porous nature of gyroid materials enhances bone ingrowth, thereby improving implant stability within the body. This enhancement is attributed to the increased surface area of the gyroid structure, which is approximately 185% higher than that of a dense material of the same form factor. This larger surface area allows for enhanced cellular attachment and nutrient circulation facilitated by the porous channels. This study aims to evaluate the biological performance of a gyroid-based Ti6Al-4V implant material compared to a dense alloy counterpart. Cellular viability was assessed using the lactate dehydrogenase (LDH) assay, which demonstrated that the gyroid surface allowed marginally higher viability than dense material. The in vivo integration was studied over 6 weeks using a rabbit tibia model and characterized using X-ray, micro-CT, and histopathological examination. With a metal volume of 8.1%, the gyroid exhibited a bone volume/total volume (BV/TV) ratio of 9.6%, which is 11-fold higher than that of dense metal (0.8%). Histological assessments revealed neovascularization, in-bone growth, and the presence of a Haversian system in the gyroid structure, hinting at superior osteointegration.

A comparative study on the effects of biodegradable high-purity magnesium screw and polymer screw for fixation in epiphyseal trabecular bone.

With mechanical strength close to cortical bone, biodegradable and osteopromotive properties, magnesium (Mg)-based implants are promising biomaterials for orthopedic applications. However, during the degradation of such implants, there are still concerns on the potential adverse effects such as formation of cavities, osteolytic phenomena and chronic inflammation. Therefore, to transform Mg-based implants into clinical practice, the present study evaluated the local effects of high-purity Mg screws (HP-Mg, 99.99 wt%) by comparing with clinically approved polylactic acid (PLA) screws in epiphyseal trabecular bone of rabbits. After implantation of screws at the rabbit distal femur, bone microstructural, histomorphometric and biomechanical properties were measured at various time points (weeks 4, 8 and 16) using micro-CT, histology and histomorphometry, micro-indentation and scanning electron microscope. HP-Mg screws promoted peri-implant bone ingrowth with higher bone mass (BV/TV at week 4: 0.189 ± 0.022 in PLA group versus 0.313 ± 0.053 in Mg group), higher biomechanical properties (hardness at week 4: 35.045 ± 1.000 HV in PLA group versus 51.975 ± 2.565 HV in Mg group), more mature osteocyte LCN architecture, accelerated bone remodeling process and alleviated immunoreactive score (IRS of Ram11 at week 4: 5.8 ± 0.712 in PLA group versus 3.75 ± 0.866 in Mg group) as compared to PLA screws. Furthermore, we conducted finite element analysis to validate the superiority of HP-Mg screws as orthopedic implants by demonstrating reduced stress concentration and uniform stress distribution around the bone tunnel, which led to lower risks of trabecular microfractures. In conclusion, HP-Mg screws demonstrated greater osteogenic bioactivity and limited inflammatory response compared to PLA screws in the epiphyseal trabecular bone of rabbits. Our findings have paved a promising way for the clinical application of Mg-based implants.

Creating an extracellular matrix-like three-dimension structure to enhance the corrosion resistance and biological responses of titanium implants

Background/purposeTitanium (Ti) is extensively used in dental and orthopedic implants due to its excellent mechanical properties. However, its smooth and biologically inert surface does not support the ingrowth of new bone, and Ti ions may have adverse biological effects. The purpose is to improve the corrosion resistance of titanium and create a 3D structured coating to enhance osseointegration through a very simple and fast surface treatment. Materials and methodsThis study investigated the use of sandblasting, acid etching, and NaOH leaching to produce porous Ti implants with enhanced biological activity and corrosion resistance. ResultsThese surface modifications generated a mixed oxide layer resembling the extracellular matrix (ECM), consisting of a dense amorphous TiO2 inner layer (50–100 nm thick) and a TiO2 outer layer with interconnected pores (pore size 50–500 nm; 150–200 nm thick). The inner layer significantly improved corrosion resistance, while the hydrophilic outer layer, with its porous structure, facilitated protein albumin adsorption and promoted the attachment, proliferation, and mineralization of human bone marrow mesenchymal stem cells. ConclusionThe combined surface treatment approach of sandblasting, acid etching, and NaOH leaching offers a comprehensive solution to the challenges associated with titanium implants' biological inertness and corrosion susceptibility. By enhancing both the biological activity and corrosion resistance of Ti surfaces, this protocol holds significant promise for improving dental and orthopedic implants' success rates and longevity. Future studies should focus on in vivo assessments and long-term clinical trials to further validate these findings and explore the potential for widespread clinical adoption.