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Anisotropic Biomimetic Trabecular Porous Three-Dimensional-Printed Ti-6Al-4V Cage for Lumbar Interbody Fusion
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Spinal fusion surgeries are performed to treat a multitude of cervical and lumbar diseases that lead to pain and disability. Spinal interbody fusion involves inserting a cage between the spinal vertebrae, and is often utilized for indirect neurologic decompression, correction of spinal alignment, anterior column stability, and increased fusion rate. The long‐term success of interbody fusion relies on complete osseointegration between the implant surface and vertebral end plates. Titanium (Ti)‐based alloys and polyetheretherketone (PEEK) interbody cages represent the most commonly utilized materials and provide sufficient mechanics and biocompatibility to assist in fusion. However, modification to the surface and bulk characteristics of these materials has been shown to maximize osseointegration and long‐term stability. Specifically, the introduction of intrinsic porosity and surface roughness has been shown to affect spinal interbody mechanics, vascularization, osteoblast attachment, and ingrowth potential. This narrative review synthesizes the mechanical, in vitro, in vivo, and clinical effects on fusion efficacy associated with introduction of porosity in Ti (neat and alloy) and PEEK intervertebral implants.
In recent years, interbody fusion cages have played an important role in interbody fusion surgery for treating diseases like disc protrusion and spondylolisthesis. However, traditional cages cannot achieve satisfactory results due to their unreasonable design, poor material biocompatibility, and induced osteogenesis ability, limiting their application. There are currently 3 ways to improve the fusion effect, as follows. First, the interbody fusion cage is designed to facilitate bone ingrowth through the preliminary design. Second, choose interbody fusion cages made of different materials to meet the variable needs of interbody fusion. Finally, complete post-processing steps, such as coating the designed cage, to achieve a suitable osseointegration microstructure, and add other bioactive materials to achieve the most suitable biological microenvironment of bone tissue and improve the fusion effect. The focus of this review is on the design methods of interbody fusion cages, a comparison of the advantages and disadvantages of various materials, the influence of post-processing techniques and additional materials on interbody fusion, and the prospects for the future development of interbody fusion cages.
Intervertebral cages made of Ti6Al4V alloy show excellent osteoconductivity, but also higher stiffness, compared to commonly used polyether-ether-ketone (PEEK) materials, that may lead to a stress-shielding effect and implant subsidence. In this study, a metallic intervertebral fusion cage, with improved mechanical behavior, was manufactured by the introduction of a three-dimensional (3D) mesh structure to Ti6Al4V material, using an additive manufacturing method. Then, the mechanical and biological properties of the following were compared: (1) PEEK, with a solid structure, (2) 3D-printed Ti6Al4V, with a solid structure, and (3) 3D-printed Ti6Al4V, with a mesh structure. A load-induced subsidence test demonstrated that the 3D-printed mesh Ti6Al4V cage had significantly lower tendency (by 15%) to subside compared to the PEEK implant. Biological assessment of the samples proved that all tested materials were biocompatible. However, both titanium samples (solid and mesh) were characterized by significantly higher bioactivity, osteoconductivity, and mineralization ability, compared to PEEK. Moreover, osteoblasts revealed stronger adhesion to the surface of the Ti6Al4V samples compared to PEEK material. Thus, it was clearly shown that the 3D-printed mesh Ti6Al4V cage possesses all the features for optimal spinal implant, since it carries low risk of implant subsidence and provides good osseointegration at the bone-implant interface.
Metal additive manufacturing (AM) has led to an evolution in the design and fabrication of hard tissue substitutes, enabling personalized implants to address each patient's specific needs. In addition, internal pore architectures integrated within additively manufactured scaffolds, have provided an opportunity to further develop and engineer functional implants for better tissue integration, and long-term durability. In this review, the latest advances in different aspects of the design and manufacturing of additively manufactured metallic biomaterials are highlighted. After introducing metal AM processes, biocompatible metals adapted for integration with AM machines are presented. Then, we elaborate on the tools and approaches undertaken for the design of porous scaffold with engineered internal architecture including, topology optimization techniques, as well as unit cell patterns based on lattice networks, and triply periodic minimal surface. Here, the new possibilities brought by the functionally gradient porous structures to meet the conflicting scaffold design requirements are thoroughly discussed. Subsequently, the design constraints and physical characteristics of the additively manufactured constructs are reviewed in terms of input parameters such as design features and AM processing parameters. We assess the proposed applications of additively manufactured implants for regeneration of different tissue types and the efforts made towards their clinical translation. Finally, we conclude the review with the emerging directions and perspectives for further development of AM in the medical industry.
In vitro, cellular processing on polymeric surfaces is fundamental to the development of biosensors, scaffolds for tissue engineering and transplantation. However, the effect of surface energy and roughness on the cell-surface interaction remains inconclusive, indicating a lack of complete understanding of the phenomenon. Here, we study the effect of surface energy (E s) and roughness ratio (r) of a polydimethylsiloxane (PDMS) substrate on cell attachment, growth, and proliferation. We considered two different cell lines, HeLa and MDA MB 231, and rough PDMS surfaces of different surface energy in the range E s ¼ 21-100 mJ m À2 , corresponding to WCA 161-1 , and roughness ratio in the range r ¼ 1.05-3, corresponding to roughness 5-150 nm. We find that the cell attachment process proceeds through three different stages marked by an increase in the number of attached cells with time (stage I), flattening of cells (stage II), and elongation of cells (III) on the surface. Our study reveals that moderate surface energy (E s z 70 mJ m À2) and intermediate roughness ratio (r z 2) constitute the most favourable conditions for efficient cell adhesion, growth, and proliferation. A theoretical model based on the minimization of the total free energy of the cell-substrate system is presented and is used to predict the spread length of cells that compares well with the corresponding experimental data within 10%. The performance and reusability of the rough PDMS surface of moderate energy and roughness prepared via facile surface modification are compared with standard T-25 cell culture plates for cell growth and proliferation, which shows that the proposed surface is an attractive choice for efficient cell culture.
Background
We developed a porous Ti alloy/PEEK composite interbody cage by utilizing the advantages of polyetheretherketone (PEEK) and titanium alloy (Ti alloy) in combination with additive manufacturing technology.
Methods
Porous Ti alloy/PEEK composite cages were manufactured using various controlled porosities. Anterior intervertebral lumbar fusion and posterior augmentation were performed at three vertebral levels on 20 female pigs. Each level was randomly implanted with one of the five cages that were tested: a commercialized pure PEEK cage, a Ti alloy/PEEK composite cage with nonporous Ti alloy endplates, and three composite cages with porosities of 40, 60, and 80%, respectively. Micro-computed tomography (CT), backscattered-electron SEM (BSE-SEM), and histological analyses were performed.
Results
Micro-CT and histological analyses revealed improved bone growth in high-porosity groups. Micro-CT and BSE-SEM demonstrated that structures with high porosities, especially 60 and 80%, facilitated more bone formation inside the implant but not outside the implant. Histological analysis also showed that bone formation was higher in Ti alloy groups than in the PEEK group.
Conclusion
The composite cage presents the biological advantages of Ti alloy porous endplates and the mechanical and radiographic advantages of the PEEK central core, which makes it suitable for use as a single implant for intervertebral fusion.
Purpose:
Lumbar interbody fusion (LIF) is a treatment option for low back pain secondary to lumbar instability and/or deformity. This review highlights recent studies of surgical techniques and bone healing strategies for LIF.
Methods:
Relevant articles were identified by searching the PubMed database from January 1948 to April 2020, with a focus on the last 5 years, using the following keywords: LIF approach, LIF cage, stem cells for LIF, biomaterials for LIF, and osteobiologics for LIF.
Results:
LIF procedures were traditionally performed through either a posterior approach (PLIF), or an anterior approach. Later, the transforaminal LIF approach gained popularity over the PLIF as it entailed less nerve retraction. To minimize paraspinal muscle dissections, alternative approaches including lateral LIF, oblique LIF, and minimally invasive approaches have been developed and utilized. These modifications have improved the surgical outcomes of LIF. However, the most recent rates of non-union after LIF procedures still ranged from 7 to 20% with an even higher incidence in patients with osteoporosis. This review summarizes the advantages and disadvantages of each surgical approach and current efforts to enhance LIF by improving fusion cage material properties and developing novel osteobiologic products that contain nanomaterials for controlled release of effective osteogenic proteins and mesenchymal stem cells.
Conclusions:
There have been significant advances in surgical technologies for LIF over the past decades. Post-operative non-union remains a major challenge, which could be addressed by development of more effective surgical techniques, fusion cages, and bone healing products through joint efforts from spine surgeons, bone biologists, and material engineers.
Introduction: Implant subsidence is a potential complication of spinal interbody fusion and may negatively affect patients subjected to procedures relying on indirect decompression such as minimally invasive transpsoas lateral lumbar interbody fusion (LLIF). The porous architecture of a recently developed titanium intervertebral cage maximizes bone-to-implant contact and minimizes stress shielding in laboratory experiments; however, its subsidence rate in patients has not yet been evaluated. The goal of this current study was to evaluate implant subsidence in patients subjected to LLIF.
Methods: Our institutional review board-approved single-center experience included 29 patients who underwent 30 minimally invasive LLIF from July 2017 to September 2018 utilizing the novel 3D-printed porous titanium implants. Radiographs, obtained during routine postoperative follow-up visits, were reviewed for signs of implant subsidence, defined as any appreciable compromise of the vertebral endplates.
Results: Radiographic subsidence occurred in 2 cases (6.7%), involving 2 out of 59 porous titanium interbody cages (3.4%). Both cases of subsidence occurred in four-level stand-alone constructs. The patients remained asymptomatic and did not require surgical revision. Ten surgeries were stand-alone constructs, and 20 surgeries included supplemental posterior fixation.
Conclusions: In our patient cohort, subsidence of the porous titanium intervertebral cage occurred in 6.7% of all cases and in 3.4% of all lumbar levels. This subsidence rate is lower compared to previously reported subsidence rates in patients subjected to LLIF using polyetheretherketone implants.
Long‐term and stable fixation of implants is one of the most important points for a successful orthopedic surgery in the field of endoprosthesis. Osseointegration, functional connection between bone and implants, is considered as a pivotal process of cementless implant fixation and integration, respectively. Osseointegration is affected by various factors of which the property of implants is of high significance. The modification of implants surface for better osseointegration has raised increasing attention in modern orthopedic medicine. Here, the process of osseointegration and the interactions between implants and ambient bone tissues were emblazed. The knowledge regarding the contemporary surface modification strategies was systematically analyzed and reviewed, including materials used for the fabrication of implants, advanced modification techniques, and key factors in the design of porous implants structure. We discussed the superiority of current surface modification programs and concluded the problems remain to be solved. The primary intention of this systematic review is to provide comprehensive reference information and an extensive overview for better fabrication and design of orthopedic implants. This article is protected by copyright. All rights reserved.
A broad range of synthetic trabecular-like metallic lattices are 3D printed, to study the extra design free-dom conferred by this new manufacturing process. The aim is to propose new conceptual types of implant structures for superior bio-mechanical matching and osseo-integration: synthetic bone. The target designs are 3D printed in Ti-6Al-4V alloy using a laser-bed process. Systematic evaluation is then carried out: (i) their accuracy is characterised at high spatial resolution using computed X-ray tomography, to assess manufacturing robustness with respect to the original geometrical design intent and (ii)the mechanical properties – stiffness and strength – are experimentally measured, evaluated, and com-pared. Finally, this new knowledge is synthesised in a conceptual framework to allow the construction of so-called implant design maps, to define the processing conditions of bone tailored substitutes, with focus on spine fusion devices. The design criteria emphasise the bone stiffness-matching, preferred range of pore structure for bone in-growth, manufacturability of the device and choice of inherent materials properties which are needed for durable implants. Examples of the use of such maps are given with focus on spine fusion devices, emphasising the stiffness-matching, osseo-integration properties and choice of inherent materials properties which are needed for durable implants .
Scaffold designing for cartilage tissue engineering requires suitable physico-mechanical and biological properties. This research was carried out to study the effects of β-tricalcium phosphate nanoparticles (β-TCP) on Poly (3-hydroxybutyrate) (PHB)-chitosan (Cs) electrospun scaffold. Results showed that the addition of different amounts of β-TCP increased fibre diameter, porosity, hydrophilicity and tensile strength in the proper condition. An increase in the degradation rate was observed by an increase in the amount of β-TCP. The biological behaviour of the PHB-Cs/7.5%wt β-TCP electrospun nanocomposite scaffold was investigated through the formation of apatite-like granules and proper attachment and proliferation of chondrocytes on the surface of scaffolds.
Study Design
Meta-analysis-based calculation.
Objectives
Lumbar degenerative spine disease (DSD) is a common cause of disability, yet a reliable measure of its global burden does not exist. We sought to quantify the incidence of lumbar DSD to determine the overall worldwide burden of symptomatic lumbar DSD across World Health Organization regions and World Bank income groups.
Methods
We used a meta-analysis to create a single proportion of cases of DSD in patients with low back pain (LBP). Using this information in conjunction with LBP incidence rates, we calculated the global incidence of individuals who have DSD and LBP (ie, their DSD has neurosurgical relevance) based on the Global Burden of Disease 2015 database.
Results
We found that 266 million individuals (3.63%) worldwide have DSD and LBP each year; the highest and lowest estimated incidences were found in Europe (5.7%) and Africa (2.4%), respectively. Based on population sizes, low- and middle-income countries have 4 times as many cases as high-income countries. Thirty-nine million individuals (0.53%) worldwide were found to have spondylolisthesis, 403 million (5.5%) individuals worldwide with symptomatic disc degeneration, and 103 million (1.41%) individuals worldwide with spinal stenosis annually.
Conclusions
A total of 266 million individuals (3.63%) worldwide were found to have DSD and LBP annually. Significantly, data quality is higher in high-income countries, making overall quantification in low- and middle-income countries less complete. A global effort to address degenerative conditions of the lumbar spine in regions with high demand is important to reduce disability.
Background context:
There is significant variability in the materials commonly used for interbody cages in spine surgery. It is theorized that 3-D printed interbody cages utilizing porous titanium material can provide more consistent bone ingrowth and biological fixation.
Purpose:
The purpose of this study was to provide an evidence-based approach to decision making regarding interbody materials for spinal fusion.
Study design:
Comparative animal study.
Methods:
A skeletally mature ovine lumbar fusion model was utilized for this study. Interbody fusions were performed at (L2-L3 and L4-L5) in 27 mature sheep using three different interbody cages (i.e., polyetheretherketone [PEEK], plasma sprayed porous titanium coated PEEK [PSP], and 3-D printed porous titanium alloy cage [PTA]). Non-destructive kinematic testing was performed in the three primary directions of motion. The specimens were then analyzed using micro-computed tomography (µCT); quantitative measures of the bony fusion were performed. Histomorphometric analyses were also performed in the sagittal plane through the interbody device. Outcome parameters were compared between cage designs and time-points.
Results:
Flexion-extension range of motion (ROM) was statistically reduced for the PTA group as compared to the PEEK cages at 16 weeks (p-value = 0.02). Only the PTA cages demonstrated a statistically significant decrease in ROM and increase in stiffness across all three loading directions between the 8-week and 16-week sacrifice time-points (p-value ≤ 0.01). Micro-CT data demonstrated significantly greater total bone volume within the graft window for the PTA cages at both 8-weeks and 16-weeks compared to the PEEK cages (p-value < 0.01).
Conclusions:
A direct comparison of interbody implants demonstrates significant and measurable differences in biomechanical, µCT, and histologic performance in an ovine model. The 3-D printed porous titanium interbody cage resulted in statistically significant reductions in ROM, increases in the bone ingrowth profile, as well as average construct stiffness compared to PEEK and PSP.
Calcium phosphate cements (CPCs) are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre-vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis.
Purpose of review:
Lateral lumbar interbody fusion (LLIF) is a relatively new, minimally invasive technique for interbody fusion. The goal of this review is to provide a general overview of LLIF with a special focus on outcomes and complications.
Recent findings:
Since the first description of the technique in 2006, the indications for LLIF have expanded and the rate of LLIF procedures performed in the USA has increased. LLIF has several theoretical advantages compared to other approaches including the preservation of the anterior and posterior annular/ligamentous structures, insertion of wide cages resting on the dense apophyseal ring bilaterally, and augmentation of disc height with indirect decompression of neural elements. Favorable long-term outcomes and a reduced risk of visceral/vascular injuries, incidental dural tears, and perioperative infections have been reported. However, approach-related complications such as motor and sensory deficits remain a concern. In well-indicated patients, LLIF can be a safe procedure used for a variety of indications.
The purpose of this work is the morphological.11 characterization of a Voronoi-based biomimetic bone scaffold, developed through an interactive generative design process and obtained by an additive manufacturing system. In particular, the assessment of its characteristics was carried out according to the main indices of trabecular bone structures. Therefore, a biomimetic cubic bone scaffold (\(10\times 10\times 10\) mm) with controlled porosity (P% = 80%) and mean pores size (\(D_{p}=0.800\,\hbox { mm}\)) was first designed and then manufactured with Ti6Al4V by means of EOSINT M270, a direct metal laser sintering system. The surface morphology of the scaffold was analyzed by a Scanning Electron Microscopy, equipped with an Energy Dispersive X-ray Spectrometry, while the internal morphology was examined through a high-resolution micro-CT SkyScan 1172. Finally, the morphometric assessment of the scaffold was carried out using ImageJ with BoneJ, a tool for image bone analysis, by measuring the main indices for the characterization of trabecular bone structure. The Ti6Al4V scaffold, even though with smaller porosity (P% = 73%) and mean pores size (\(D_{p}=0.695 \hbox { mm}\)) with respect to the expected values, was successfully fabricated with fully interconnected porous architecture and intact trabecular skeleton. Moreover, the main indices for the characterization of trabecular bone structure were well congruent with the actual natural bone. A viable and reproducible method to fabricate Ti6Al4V biomimetic bone scaffolds, with controlled porosity and mean pores size, was presented. These kind of scaffolds allowed reproducing the actual architecture of the trabecular bone and could be suitable for Bone Tissue Engineering, according to specific surgical requirements.
We elucidate here process-structure-property relationships in implantable biomaterials processed by rapid prototyping approaches that are based on the principle of additive manufacturing. The conventional methods of fabrication of biomedical devices including freeze casting and sintering are limited because of difficulties in adaptation at the host site and mismatch in micro/ macrostructure, mechanical and physical properties with the host tissue. Moreover, additive manufacturing has the advantage of fabricating patient-specific designs, which can be obtained from the computed tomography scan of the defect site. The discussion here comprises two parts - the first part briefly describes the evolution and underlying reasons that have led to 3D printing of scaffolds for tissue regeneration. The second part focuses on biocompatibility and mechanical properties of 3D scaffolds, fabricated by different approaches. The article concludes with a discussion on functionally graded scaffolds and vascularisation of 3D porous scaffolds that are envisaged to meet the requirements of the biomedical industry. In general, the mechanical properties of 3D printed scaffolds are governed by pore architecture, pore volume and percentage porosity. To ensure long-term endurance and the ability to withstand abrupt impact, it is important that the fabricated materials have a good combination of strength and energy absorption capability. While scaffolds with high interconnected porosity are preferred for tissue regeneration, such structures lack adequate mechanical strength and energy absorption capability. These mutually opposing requirements of high porosity and mechanical strength in conjunction with high energy absorption have hindered the application of 3D scaffolds as biomedical devices. In this regard, functionally graded 3D structures with high strength and energy absorption are potentially attractive for biomedical devices. © 2016 Institute of Materials, Minerals and Mining and ASM International.
Rapid and stable fixation at the bone-implant interface would be regarded as one of the primary goals to achieve clinical efficacy regardless of the surgical site. Whilst mechanical and physical properties of polyetheretherketone (PEEK) provide advantages for implant devices, the hydrophobic nature and lack of direct bone contact remains a limitation.
This study examined the effects of a titanium plasma sprayed coating to PEEK on the mechanical and histological properties at the bone - implant interface.
Pre-clinical laboratory study.
PEEK and plasma sprayed titanium coated PEEK implants (Ti-Bond, Spinal Elements, Carlsbad, CA) were placed in a line to line manner in cortical bone and press fit in cancellous bone of adult sheep using an established ovine model. Shear strength was assessed in the cortical sites at 4 and 12 weeks while histology was performed in cortical and cancellous sites at both time points.
The titanium coating dramatically improved the shear strength at the bone implant interface at 4 weeks and continued to improve with time compared to PEEK. Direct bone ongrowth in cancellous as well as cortical sites can be achieved using a plasma sprayed titanium coating on PEEK.
Direct bone to implant bonding can be achieved on PEEK in spite of its hydrophobic nature using a plasma sprayed titanium coating. The plasma sprayed titanium coating improved mechanical properties in cortical sites as well as the histology in cortical and cancellous site.
Copyright © 2014 Elsevier Inc. All rights reserved.
Motivated by the successful fabrication of patient-specific biomedical implants that can potentially replace hard tissue (bone), particularly knee and hip stems and large femoral intramedullary rods, using additive manufacturing by electron beam melting (Murr et al. Phil. Trans. R.
Soc. A 2010; 22:1999–2032), we describe here the combined efforts of engineering and biological sciences as a systemic approach to study osteoblast functions of 3D mesh arrays with particular focus on pore size and the potential to use 3D fabricated porous biomedical devices for bone
healing. First, the interconnecting porous architecture of monolithic mesh arrays was conducive to cellular functions including attachment, proliferation, differentiation, and mineralization. The underlying reason is that the fabricated structure provided a channel for initiation of cell migration
and impregnation of the mesh structure by cells and tissue leading to generation of mineralized extracellular matrix by differentiating pre-osteoblasts. Second, a parametric study on the interconnecting pore diameter of mesh arrays indicated that the average pore diameters studied (∼400–800
μm) had no apparent effect on the differentiation and mineralization, and influenced only the proliferation phase. Third, from the biomechanical point of view, the cell-invaded and cell-integrated 3D mesh structure and resulted in the superior formation of tissue.
Additive manufacturing by laser sintering is able to produce high resolution metal constructs for orthopedic and dental implants. In this study, we used a human trabecular bone template to design and manufacture Ti-6Al-4V constructs with varying porosity via laser sintering. Characterization of constructs revealed interconnected porosities ranging from 15–70% with compressive moduli of 2579–3693 MPa. These constructs with macro porosity were further surface-treated to create a desirable multi-scale micro-/nano-roughness, which has been shown to enhance the osseointegration process. Osteoblasts (MG63 cells) exhibited high viability when grown on the constructs. Proliferation (DNA) and alkaline phosphatase specific activity, an early differentiation marker, decreased as porosity increased, while osteocalcin, a late differentiation marker, as well as osteoprotegerin, vascular endothelial growth factor and bone morphogenetic proteins 2 and 4 increased with increasing porosity. Three-dimensional (3D) constructs with the highest porosity and surface modification supported the greatest osteoblast differentiation and local factor production. These results indicate that additively manufactured 3D porous constructs mimicking human trabecular bone and produced with additional surface treatment can be customized for increased osteoblast response. Increased factors for osteoblast maturation and differentiation on high porosity constructs suggest the enhanced performance of these surfaces for increasing osseointegration in vivo.
Titanium (Ti) and Ti alloys are used in orthopaedic/spine applications where biological implant fixation, or osseointegration, is required for long-term stability. These implants employ macro-scale features to provide mechanical stability until arthrodesis, features that are too large to influence healing at the cellular level. Micron-scale rough Ti alloy (Ti-6Al-4V) increases osteoblastic differentiation and osteogenic factor production in vitro and increases in vivo bone formation; however, effects of overall topography, including sub-micron scale and nanoscale features, on osteoblast lineage cells are less well appreciated. To address this, Ti6Al4V surfaces with macro/micro/nano-textures were generated using sand blasting and acid etching that had comparable average roughness values but differed in other roughness parameters (total roughness, profile roughness, maximum peak height, maximum valley depth, root-mean-squared roughness, kurtosis, skewness) (#5, #9, and #12). Human mesenchymal stem cells (HMSCs) and normal human osteoblasts (NHOst) were cultured for 7 days on the substrates and then analyzed for alkaline phosphatase activity and osteocalcin content, production of osteogenic local factors, and integrin subunit expression. All three surfaces supported osteoblastic differentiation of HMSCs and further maturation of NHOst cells, but the greatest response was seen on the #9 substrate, which had the lowest skewness and kurtosis. The #9 surface also induced highest expression of α2 and β1 integrin mRNA. HMSCs produced highest levels of ITGAV on #9, suggesting this integrin may play a role for early lineage cells. These results indicate that osteoblast lineage cells are sensitive to specific micro/nanostructures, even when overall macro roughness is comparable and suggest that skewness and kurtosis are important variables.
BACKGROUND CONTEXT
Cage subsidence remains a serious complication after spinal fusion surgery. Novel porous designs in the cage body or endplate offer attractive options to improve subsidence and osseointegration performance.
PURPOSE
To elucidate the relative contribution of a porous design in each of the two major domains (body and endplates) to cage stiffness and subsidence performance, using standardized mechanical testing methods, and to analyze the fusion progression via an established ovine interbody fusion model to support the mechanical testing findings.
STUDY DESIGN/SETTING
A comparative preclinical study using standardized mechanical testing and established animal model.
METHODS
To isolate the subsidence performance contributed by each porous cage design feature, namely the stress-optimized body lattice (vs. a solid body) and microporous endplates (vs. smooth endplates), four groups of cages (two-by-two combination of these two features) were tested in: 1) static axial compression of the cage (per ASTM F2077) and 2) static subsidence (per ASTM F2267). To evaluate the progression of fusion, titanium cages were created with a microporous endplate and internal lattice architecture analogous to commercial implants used in subsidence testing and implanted in an endplate-sparing, ovine intervertebral body fusion model.
RESULTS
The cage stiffness was reduced by 16.7% by the porous body lattice, and by 16.6% by the microporous endplates. The porous titanium cage with both porous features showed the lowest stiffness with a value of 40.4 ± 0.3 kN/mm (Mean ± SEM) and a block stiffness of 1976.8 ± 27.4 N/mm for subsidence. The body lattice showed no significant impact on the block stiffness (1.4% reduction), while the microporous endplates decreased the block stiffness significantly by 24.9% (p<0.0001). All segments implanted with porous titanium cages were deemed rigidly fused by manual palpation, except one at 12 weeks, consistent with robotic ROM testing and radiographic and histologic observations. A reduction in ROM was noted from 12 to 26 weeks (4.1±1.6° to 2.2±1.4° in lateral bending, p<0.05; 2.1±0.6° to 1.5±0.3° in axial rotation, p<0.05); and 3.3±1.6° to 1.9±1.2° in flexion extension, p=0.07). Bone in the available void improved with time in the central aperture (54±35% to 83±13%, p<0.05) and porous cage structure (19±26% to 37±21%, p=0.15).
CONCLUSIONS
Body lattice and microporous endplates features can effectively reduce the cage stiffness, therefore reducing the risk of stress shielding and promoting early fusion. While body lattice showed no impact on block stiffness and the microporous endplates reduced the block stiffness, a titanium cage with microporous endplates and internal lattice supported bone ingrowth and segmental mechanical stability as early as 12 weeks in ovine interbody fusion.
CLINICAL SIGNIFICANCE
Porous titanium cage architecture can offer an attractive solution to increase the available space for bone ingrowth and bridging to support successful spinal fusion while mitigating risks of increased subsidence
Optimization of porous titanium alloy scaffolds designed for orthopedic implants requires balancing mechanical properties and osseointegrative performance. The tradeoff between scaffold porosity and stiffness/strength which must be optimized towards the goal to improve long term load sharing while simultaneously promoting osseointegration. Osseointegration into porous titanium implants covering a wide range of porosity (0%–90%) and manufactured by laser powder bed fusion (LPBF) was evaluated with an established ovine cortical and cancellous defect model. Direct apposition and remodeling of woven bone was observed at the implant surface, as well as bone formation within the interstices of the pores. A linear relationship was observed between the porosity and benchtop mechanical properties of the scaffolds, while a non-linear relationship was observed between porosity and the ex vivo cortical bone-implant interfacial shear strength. Our study supports the hypothesis of porosity dependent performance tradeoffs and establishes generalized relationships between porosity and performance for design of topological optimized implants for osseointegration. These results are widely applicable for orthopedic implant design for arthroplasty components, arthrodesis devices such as spinal interbody fusion implants, and patient matched implants for treatment of large bone defects.
One of the main biomechanical causes for aseptic failure of orthopaedic implants is the stress shielding. This is caused by an uneven load distribution across the bone normally due to a stiff metal prosthesis component, leading to periprosthetic bone resorption and to implant loosening. To reduce the stress shielding and to improve osseointegration, biocompatible porous structures suitable for orthopaedic applications have been developed. Aim of this study was to propose a novel in-vitro model of the mechanical interaction between metal lattice structures and bovine cortical bone in compression. Analysis of the strain distribution between metal structure and bone provides useful information on the potential stress shielding of orthopaedic implants with the same geometry of the porous scaffold. Full density and lattice structures obtained by the repetition of 1.5 mm edge cubic elements via Laser Powder Bed Fusion of CoCrMo powder were characterized for mechanical properties using standard compressive testing. The two porous geometries were characterized by 750 μm and 1000 μm pores resulting in a nominal porosity of 43.5% and 63.2% respectively. Local deformation and strains of metal samples coupled with fresh bovine cortical bone samples were evaluated via Digital Image Correlation analysis up to failure in compression. Visualization and quantification of the local strain gradient across the metal-bone interface was used to assess differences in mechanical behaviour between structures which could be associated to stress-shielding. Overall stiffness and local mechanical properties of lattice and bone were consistent across samples. Full-density metal samples appeared to rigidly transfer the compression force to the bone which was subjected to large deformations (2.2 ± 0.3% at 15 kN). Larger porosity lattice was associated to lower stiffness and compressive modulus, and to a smoother load transfer to the bone. While tested on a limited sample size, the proposed in-vitro model appears robust and repeatable to assess the local mechanical interaction of metal samples suitable for orthopaedic applications with the bone tissue. CoCrMo scaffolds made of 1000 μm pores cubic cells may allow for a smoother load transfer to the bone when used as constitutive material of orthopaedic implants.
Background context:
Osseointegration is a pivotal process in achieving a rigid fusion and ultimately a successful clinical outcome following interbody fusion surgery. Advancements in 3D printing technology permit commonly used titanium interbody spacers to be designed with unique architectures, such as a highly interconnected and specific porous structure that mimics the architecture of trabecular bone. Interbody implants with a microscale surface roughness and biomimetic porosity may improve bony ongrowth and ingrowth compared to traditional materials.
Purpose:
The purpose of this study was to compare the osseointegration of lumbar interbody fusion devices composed of surgical-grade polyetheretherketone (PEEK), titanium-alloy (TAV), and 3D-printed porous, biomimetic TAV (3DP) using an in vivo ovine model.
Study design:
In Vivo Preclinical Animal Study METHODS: Eighteen sheep underwent two-level lateral lumbar interbody fusion randomized with either 3DP, PEEK, or TAV interbody spacers (n=6 levels for each spacer per time point). Postoperative time points were 6 and 12 weeks. Microcomputed tomography and histomorphometry were used to quantify bone volume (BV) within the spacers (ingrowth) and the surface bone apposition ratio (BAR) (ongrowth), respectively.
Results:
The 3DP-treatment group demonstrated significantly higher BV than the PEEK and TAV groups at 6 weeks (77.3±44.1 mm3, 116.9±43.0 mm3, and 108.7±15.2 mm3, respectively) (p<0.05). At 12 weeks, there were no BV differences between groups (p>0.05). BV increased in all groups from the 6- to 12-week time points (p<0.05). At both time points, the 3DP-treated group (6w: 23.6±10.9%; 12w: 36.5±10.9%) had significantly greater BAR than the PEEK (6w: 8.6±2.1%; 12w: 14.0±5.0%) and TAV (6w: 6.0±5.7%; 12w: 4.1±3.3%) groups (p<0.05).
Conclusions:
3DP interbody spacers facilitated greater total bony ingrowth at 6 weeks, and greater bony ongrowth postoperatively at both 6 and 12 weeks, in comparison to solid PEEK and TAV implants.
Clinical significance:
Based on these findings, the 3DP spacers may be a reasonable alternative to traditional PEEK and TAV spacers in various clinical applications of interbody fusion.
Orthopedic implants with heterogeneous porous structures were known as ideal bone osteointegration. This research introduced the selective laser melting (SLM), finite element analysis (FEA), and a hydrothermal process (HT) for manufacturing a three-level heterogeneous porous structure. The macroporous structure was designed via CAD and micropores were tuned via laser power regulation. A nano-size layer of hydroxyapatite crystals was coated by an HT process. The mechanical properties were reinforced via a core-shell structure with core reinforcement. The existence of micropores and nano-hydroxyapatite coating enhanced the in vitro proliferation of preosteoblasts and osteogenic cellular behaviors of rBMSCs. Thus, the three-level heterogeneous porous titanium implants could inspire researchers with potential clue of cyto-implant interaction mechanism, therefore building ideal orthopedic implants with accelerated osteointegration.
Statement of Significance
Porous structures of titanium implants play an important role in bone tissue regeneration; The geometrical environment influence cell behaviour and bone tissue ingrowth in all macro-/micro-/nanoscale. In this study, a novel method to fabricate heterogeneous scaffolds and its macro-/micro-/nanoscopic structures were studied. A CAD model was used to obtain the macroscopic structure and the insufficient laser power was introduced for porous microstructure. Therefore, a layer of nano hydroxyapatite was coated via hydrothermal process. Cytoproliferation and cytodifferentiation results indicated that a integrity of regular/irregular, macro-/micro-/nanoscale porous structure had advance in recruiting stem cells and promoting differentiation. This research is beneficial to the development of bone implants with better bone regeneration ability.
Permanent orthopedic/dental implants should reveal good osseointegration, which is defined as an ability of the biomaterial to form a direct connection with the surrounding host bone tissue after its implantation into the living organism. Currently, biomaterial osseointegration is confirmed exclusively with the use of in vivo animal tests. This study presents for the first time ex vivo determination of osseointegration process using human trabecular bone explant that was drilled and filled with the chitosan/curdlan/hydroxyapatite biomaterial, followed by its long-term culture under in vitro conditions. Within this study, it was clearly proved that tested biomaterial allows for the formation of the connection with bone explant since osteoblasts, having ability to produce bone extracellular matrix (type I collagen, fibronectin), were detected at a bone-implant interface by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Importantly, in this research it was demonstrated by Live/Dead staining and CLSM imaging that human bone explants may stay alive for a long period of time (at least approx. 50 days) during their culture under in vitro conditions. Therefore, ex vivo bone explant, which is a heterogeneous tissue containing many different cell types, may serve as an excellent model to test biomaterial osseointegration during comparative and preliminary studies, reducing animal tests which is compatible with the principles of ‘3Rs’, aiming to Replace, Reduce and Refine the use of animals wherever possible.
Porous fusion cage is considered as a satisfactory substitute for solid fusion cage in transforaminal lumbar interbody fusion (TLIF) surgery due to its interconnectivity for bone ingrowth and appropriate stiffness reducing the risk of cage subsidence and stress shielding. This study presents an integrated global-local topology optimization approach to obtain porous titanium (Ti) fusion cage with desired biomechanical properties. Local topology optimizations are first conducted to obtain unit cells, and the numerical homogenization method is used to quantified the mechanical properties of unit cells. The preferred porous structure is then fabricated using selective laser melting, and its mechanical property is further verified via compression tests and numerical simulation. Afterward, global topology optimization is used for the global layout. The porous fusion cage obtained by the Boolean intersection between global structural layout and the porous structure decreases the solid volume of the cage by 9% for packing more bone grafts while achieving the same stiffness to conventional porous fusion cage. To eliminate stress concentration in the thin-wall structure, framework structures are constructed on the porous fusion cage. Although the alleviation of cage subsidence and stress shielding is decelerated, peak stress on the cage is significantly decreased, and more even stress distribution is demonstrated in the reinforced porous fusion cage. It promises long-term integrity and functions of the fusion cage. Overall, the reinforced porous fusion cage achieves a favorable mechanical performance and is a promising candidate for fusion surgery. The proposed optimization approach is promising for fusion cage design and can be extended to other orthopedic implant designs.
Background
Lumbar interbody fusion is among the most common types of spinal surgery performed. Over time, the term has evolved to encompass a number of different approaches to the intervertebral space, as well as differing implant materials. Questions remain over which approaches and materials are best for achieving fusion and restoring disc height.
Questions/Purposes
We reviewed the literature on the advantages and disadvantages of various methods and devices used to achieve and augment fusion between the disc spaces in the lumbar spine.
Methods
Using search terms specific to lumbar interbody fusion, we searched PubMed and Google Scholar and identified 4993 articles. We excluded those that did not report clinical outcomes, involved cervical interbody devices, were animal studies, or were not in English. After exclusions, 68 articles were included for review.
Results
Posterior approaches have advantages, such as providing 360° support through a single incision, but can result in retraction injury and do not always restore lordosis or correct deformity. Anterior approaches allow for the largest implants and good correction of deformities but can result in vascular, urinary, psoas muscle, or lumbar plexus injury and may require a second posterior procedure to supplement fixation. Titanium cages produce improved osteointegration and fusion rates but also increase subsidence caused by the stiffness of titanium relative to bone. Polyetheretherketone (PEEK) has an elasticity closer to that of bone and shows less subsidence than titanium cages, but as an inert compound PEEK results in lower fusion rates and greater osteolysis. Combination PEEK–titanium coating has not yet achieved better results. Expandable cages were developed to increase disc height and restore lumbar lordosis, but the data on their effectiveness have been inconclusive. Three-dimensionally (3D)-printed cages have shown promise in biomechanical and animal studies at increasing fusion rates and reducing subsidence, but additive manufacturing options are still in their infancy and require more investigation.
Conclusions
All of the approaches to spinal fusion have plusses and minuses that must be considered when determining which to use, and newer-technology implants, such as PEEK with titanium coating, expandable, and 3D-printed cages, have tried to improve upon the limitations of existing grafts but require further study.
Backgrounds:
Disadvantages of polyetheretherketone (PEEK) cages are their smooth and hydrophobic surfaces and their lack of osteoconductivity. Titanium (Ti) coated PEEK cage has been innovated to overcome these potential concerns. However, few well-designed studies have investigated the efficacy of Ti-coated PEEK cage on interbody fusion in humans. This study aimed to evaluate the efficacy of Ti coating on bone ongrowth at bone-implant surface by simultaneously comparing Ti-coated and uncoated PEEK cages in the same intervertebral space.
Methods:
This study is a prospective comparative study for the two different cages. Twenty-six subjects who underwent one-level instrumented posterior lumbar interbody fusion (PLIF) were included. Two PEEK cages [a plasma-sprayed Ti-coated (PTC-PEEK) and an uncoated PEEK cage] were inserted in the same intervertebral space. Fusion rates, cage subsidence, and vertebral cancellous condensation (VCC) around the cage, which indicates bone growth on the surface of each cage, were assessed by thin-slice computed tomography (CT) immediately (within 1 week) and at 3 months postoperatively. A functional radiograph was obtained at 3 and 12 months postoperatively.
Results:
Twenty-three subjects showed solid fusion at 3 months postoperatively (fusion rate, 88%). Cage subsidence was not observed. VCC was often observed around the PTC-PEEK cage as evaluated by completely synchronized CT images between immediately and at 3 months postoperatively. Quantified VCC around the cage was significantly larger in the PTC-PEEK cage than in the uncoated PEEK cage (P = 0.01).
Conclusions:
The Ti-coated PEEK cage exhibits radiographic signs, suggesting bone ongrowth, as represented by VCC around the cage compared with that around the uncoated PEEK cage. The Ti-coated PEEK cage has the potential to promote solid fusion and to improve clinical outcomes in lumbar interbody fusion surgery.
Material properties of implants such as volume porosity and nanoscale surface modification have been shown to enhance cell-material interactions in vitro and osseointegration in vivo. Porous tantalum (Ta) and titanium (Ti) coatings are widely used for non-cemented implants, which are fabricated using different processing routes. In recent years, some of those implants are being manufactured using additive manufacturing. However, limited knowledge is available on direct comparison of additively manufactured porous Ta and Ti structures towards early stage osseointegration. In this study, we have fabricated porous Ta and Ti6Al4V (Ti64) implants using laser engineered net shaping (LENS™) with similar volume fraction porosity to compare the influence of surface characteristics and material chemistry on in vivo response using a rat distal femur model for 5 and 12 weeks. We have also assessed whether surface modification on Ti64 can elicit similar in vivo response as porous Ta in a rat distal femur model for 5 and 12 weeks. The harvested implants were histologically analyzed for osteoid surface per bone surface. Field emission scanning electron microscopy (FESEM) was done to assess the bone-implant interface. The results presented here indicate comparable performance of porous Ta and surface modified porous Ti64 implants towards early stage osseointegration at 5 weeks post implantation through seamless bone-material interlocking. However, a continued and extended efficacy of porous Ta is found in terms of higher osteoid formation at 12 weeks post-surgery.
Lumbar intervertebral body fusion devices (L-IBFDs) are intended to provide stability to promote fusion in patients with a variety of lumbar pathologies. Different L-IBFD designs have been developed to accommodate various surgical approaches for lumbar interbody fusion procedures including anterior, lateral, posterior, and transforaminal lumbar interbody fusions (ALIF, LLIF, PLIF, and TLIF, respectively). Due to design differences, there is a potential for mechanical performance differences between ALIF, LLIF, PLIF, and TLIF devices. To evaluate this, mechanical performance and device dimension data were collected from 124 Traditional 510(k) submissions to the FDA for L-IBFDs cleared for marketing from 2007 through 2016. From these submissions, mechanical test results were aggregated for seven commonly performed tests: static and dynamic axial compression, compression-shear, and torsion testing per ASTM F2077, and subsidence testing per ASTM F2267. The Kruskal-Wallis test and Wilcoxon signed-rank test were used to determine if device type (ALIF, LLIF, PLIF, TLIF) had a significant effect on mechanical performance parameters (static testing: stiffness and yield strength; dynamic testing: runout load; subsidence testing: stiffness [Kp]). Generally, ALIFs and LLIFs were found to be stiffer, stronger, and had higher subsidence resistance than PLIF and TLIF designs. These results are likely due to the larger footprints of the ALIF and LLIF devices. The relative mechanical performance and subsidence resistance can be considered when determining the appropriate surgical approach and implant for a given patient. Overall, the mechanical performance data presented here can be utilized for future L-IBFD development and design verification.
Triply periodic minimal surfaces (TPMS) have emerged as a suitable tool for designing porous biomaterials. One of the well-known TPMS structures is the gyroid structure. Different types of gyroid porous structures (normal and deformed gyroid structures) with different porosities have been designed and fabricated by Electron Beam Melting technology with the purpose of analysing the mechanical properties under compression and torsion loads. Then, some of them have also been studied by finite element method for different load directions. The compression tests demonstrated that the deformed gyroids presented high stiffness and strength with loads in the longitudinal direction of the structures, especially when the deformed gyroids were reinforced with a shell. The torsion tests showed that the normal gyroids presented better torsional stiffness and strength than the deformed gyroids, with high CAD porosities (90%). However, no significant differences between both structures were found for low CAD porosities (75%). Finite element analysis showed that when the loads adopted a 45° angle with regard to the longitudinal axis of the structure, the normal gyroids presented more homogeneous behaviour than the deformed gyroids. In summary, gyroid porous titanium structures presented good and versatile stiffness and strength to be used for correction of bone defects.
Ti-6Al-4V gyroid scaffolds with high porosities in the range of 82–85% and three different unit cell sizes 2, 2.5 and 3 mm were manufactured by electron beam melting (EBM) for bone implant applications. The microstructure, mechanical properties and failure mode of the scaffolds with different sample orientations were evaluated. The as-built struts showed orthogonally orientated martensite α′ needles in columnar grains along the building direction with an average hardness of 3.89 GPa and the elastic modulus and yield strength of scaffolds ranged from 637 to 1084 MPa and from 13.1 to 19.2 MPa, respectively. The elastic modulus and yield strength along the build direction and perpendicular to building direction varied by ~ 70% and 49%, respectively, depending on the amount of structural anisotropy and unit cell size. The ratio of elastic modulus anisotropy in orthogonal directions was comparable to those of trabecular bone and could be in favor of bone implant applications. Furthermore, as-built scaffolds showed a mixed mode of ductile and brittle behavior under compression, and the dominant failure mode was by forming orthogonal crush bonds at the peak loads with an angle of ~ 45° with compression axis.
In this study we describe the fabrication of a variety of open-cellular titanium alloy (TI-6Al-4V) implants, both reticular mesh and foam structures, using electron beam melting (EBM). These structures allow for the elimination of stress shielding by adjusting the porosity (or density) to produce an elastic modulus (or stiffness) to match that of both soft (trabecular) and hard (cortical) bone, as well as allowing for bone cell ingrowth, increased cell density, and all-matrix interactions; the latter involving the interplay between bone morphogenetic protein (BMP-2) and osteoblast functions. The early formation and characterization of elementary vascular structures in an aqueous hydrogel matrix are illustrated. Preliminary results for both animal (sheep) and human trials for a number of EBM-fabricated, and often patient-specific Tialloy implants are also presented and summarized. The results, while preliminary, support the concept and development of successful, porous, engineered “living” implants.
With the development of three-dimensional (3D) printing technology, porous metal scaffolds can be well fabricated. In contrast to conventional methods, 3D printing of porous scaffolds is characterized by a controllable and precise manufacturing process, which makes it possible to form customized predesigned implants for individual patients and achieve regular pore distribution at the micro scale. As the microenvironment of bone ingrowth, pores must provide sufficient space for cell attachment and proliferation. The behaviors of cells and bone ingrowth can influence the effect of 3D printed porous metal scaffolds on bone ingrowth. This review introduces 3D printing techniques shortly and focuses on the factors that potentially influence bone ingrowth into 3D printed porous metal scaffolds, e.g., materials, pore size, porosity, pore structure, surface modification, and mechanical properties. In each chapter, the mechanisms underlying cell–scaffold interactions are discussed in detail. In addition, the clinical applications of 3D printing are also introduced shortly. Finally, we list the most appropriate parameters for an excellent porous metal scaffold and attempt to identify a combination of these parameters that predicts good bone ingrowth.
Pore-scale modeling of porous media has been emphasized as a platform to study the mechanical properties, fluid storage and transport properties in it. A universal and easy-to-realize approach of structured mesh model is presented in this paper to reconstruct the three-dimensional (3D) pore scale models from the micro computed tomography (micro-CT) images. By substituting the structured hexahedron elements for the voxels in the 3D images, codes are developed to reconstruct the micro structure of porous media. The structured model is tested by the micro-CT images of four rock samples. The advantages of topology and mesh quality of this model is validated by comparisons between the PNM and unstructured mesh models. Then numerical simulations of single- and two- phase flow are conducted in Fluent software. The models are validated between the experimental data and simulation results of PNM on the absolute permeability and relative permeability curves under different conditions of sample wettability.
Porous structures, manufactured of a biocompatible metal, mimicking human bone structure are the future of orthopedic implantology. Fully porous materials, however, suffer from certain drawbacks. To overcome these, gradient in structure can be prepared. With gradient in porosity mechanical properties can be optimized to an appropriate value, implant can be attributed a similar gradient macrostructure as bone, tissue adhesion may be promoted and also various modification with organic or inorganic substances are possible. In this study, additive technology selective laser melting (SLM) was used to produce three types of gradient porosity model specimens of titanium alloy Ti-6Al-4V. As this technology has the potential to prepare complex structures in the near-net form, to control porosity, pore size and shape, it represents a promising option. The first part of the research work was focused on the characterization of the material itself in the as-produced state, only with heat treatment applied. The second part dealt with the influence of porosity on mechanical properties. The study has shown SLM brings significant changes in the surface chemistry. Despite this finding, titanium alloy retained its cytocompatibility, as it was outlined by in vitro tests with U-2 OS cells. With introduced porosity yield strength, ultimate strength and stiffness showed linear decrease, both in tension and compression. With respect to the future use in the form of orthopedic implant, especially reduction in Young's modulus down to the human bone value (30.5±2 GPa) is very appreciated as the stress-shielding effect followed by possible implant loosening is limited.
Objectives:
Low modulus β-titanium alloys with non-toxic alloying elements are envisaged to provide good biocompatibility and alleviate the undesired stress shielding effect. The objective of this study is to fundamentally elucidate the biological response of novel high strength-low elastic modulus Ti2448 alloy through the study of bioactivity and osteoblast cell functions.
Methods:
Characterization techniques such as SEM, EDX, XRD, and fluorescence microscopy were utilized to analyze the microstructure, morphology, chemical composition, and cell adhesion. The cellular activity was explored in terms of cell-to-cell communication involving proliferation, spreading, synthesis of extracellular and intracellular proteins, differentiation, and mineralization.
Results:
The formation of fine apatite-like crystals on the surface during immersion test in simulated body fluid confirmed the bioactivity of the surface, which provided the favorable osteogenic microenvironment for cell-material interaction. The proliferation and differentiation of pre-osteoblasts and their ability to form a well mineralized bone-like extracellular matrix (ECM) by secreting bone markers (ALP, calcium, etc.) over the surface point toward the determining role of unique surface chemistry and surface properties of the Ti-24Nb-4Zr-8Sn (Ti2448) alloy in modulating osteoblasts functions.
Significance:
These results demonstrated that the low modulus (∼49GPa) Ti2448 alloy with non-toxic alloying elements can be used as a potential dental or orthopedic load-bearing implant material.
We elucidate here the osteoblasts functions and cellular activity in 3D printed interconnected porous architecture of functionally gradient Ti-6Al-4V alloy mesh structures in terms of cell proliferation and growth, distribution of cell nuclei, synthesis of proteins (actin, vinculin, and fibronectin), and calcium deposition. Cell culture studies with pre-osteoblasts indicated that the interconnected porous architecture of functionally gradient mesh arrays was conducive to osteoblast functions. However, there were statistically significant differences in the cellular response depending on the pore size in the functionally gradient structure. The interconnected porous architecture contributed to the distribution of cells from the large pore size (G1) to the small pore size (G3), with consequent synthesis of extracellular matrix and calcium precipitation. The gradient mesh structure significantly impacted cell adhesion and influenced the proliferation stage, such that there was high distribution of cells on struts of the gradient mesh structure. Actin and vinculin showed a significant difference in normalized expression level of protein per cell, which was absent in the case of fibronectin. Osteoblasts present on mesh struts formed a confluent sheet, bridging the pores through numerous cytoplasmic extensions. The gradient mesh structure fabricated by electron beam melting was explored to obtain fundamental insights on cellular activity with respect to osteoblast functions.
Metallic implant materials used in load-bearing applications are inert in nature in their native state. The surface properties of the material and its interaction with the surrounding physiological fluid determine the success of the biomedical implant. In this regard, bioactive nanostructured coatings are being recognised as potential approach to enhance the biological and corrosion properties of the conventional inert materials. In this review, recent advances in biomedical applications of nanostructured hydroxyapatite coatings on stainless steel implant materials are highlighted with special focus on the electrochemical deposition of hydroxyapatite and their consequent biological activity. Furthermore, osteoblasts functions and cellular activity on the nanostructured hydroxyapatite coatings processed by other techniques is also discussed. The potential application of such next generation materials as biomedical implants is also addressed.
Additive manufacturing technique is a promising approach for fabricating cellular bone substitutes such as trabecular and cortical bones because of the ability to adjust process parameters to fabricate different shapes and inner structures. Considering the long term safe application in human body, the metallic cellular implants are expected to exhibit superior fatigue property. The objective of the study was to study the influence of cell shape on the compressive fatigue behavior of Ti-6Al-4V mesh arrays fabricated by electron beam melting. The results indicated that the underlying fatigue mechanism for the three kinds of meshes (cubic, G7 and rhombic dodecahedron) is the interaction of cyclic ratcheting and fatigue crack growth on the struts, which is closely related to cumulative effect of buckling and bending deformation of the strut. By increasing the buckling deformation on the struts through cell shape design, the cyclic ratcheting rate of the meshes during cyclic deformation was decreased and accordingly, the compressive fatigue strength was increased. With increasing bending deformation of struts, fatigue crack growth in struts contributed more to the fatigue damage of meshes. Rough surface and pores contained in the struts significantly deteriorated the compressive fatigue strength of the struts. By optimizing the buckling and bending deformation through cell shape design, Ti-6Al-4V alloy cellular solids with high fatigue strength and low modulus can be fabricated by the EBM technique.
We describe here the combined efforts of engineering and biological sciences as a systemic approach to fundamentally elucidate osteoblast functions in functionally graded Ti-6Al-4 V mesh structures in relation to uniform/monolithic mesh arrays. First, the interconnecting porous architecture of functionally graded mesh arrays was conducive to cellular functions including attachment, proliferation, and mineralization. The underlying reason is that the graded fabricated structure with cells seeded from the large pore size side provided a channel for efficient transfer of nutrients to other end of the structure (small pore size), leading to the generation of mineralized extracellular matrix by differentiating pre-osteoblasts. Second, a comparative and parametric study indicated that gradient mesh structure had a pronounced effect on cell adhesion and mineralization, and strongly influenced the proliferation phase. High intensity and near-uniform distribution of proteins (actin and vinculin) on struts of the gradient mesh structure (cells seeded from large pore side) implied signal transduction during cell adhesion and was responsible for superior cellular activity, in comparison to the uniform mesh structure and non-porous titanium alloy. Cells adhered to the mesh struts by forming a sheet, bridging the pores through numerous cytoplasmic extensions, in the case of porous mesh structures. Intercellular interaction in porous structures provided a pathway for cells to communicate and mature to a differentiated phenotype. Furthermore, the capability of cells to migrate through the interconnecting porous architecture on mesh structures led to colonization of the entire structure. Cells were embedded layer-by-layer in the extracellular matrix as the matrix mineralized. The outcomes of the study are expected to address challenges associated with the treatment of segmental bone defects and bone-remodeling through favorable modulation of cellular response. Moreover, the study provides a foundation for a new branch of functionally graded materials with interconnected porous architecture.
The aim of this work was to compare biomedical potential of chitosan/hydroxyapatite (chit/HA) and novel chitosan/β-1,3-glucan/hydroxyapatite (chit/glu/HA) materials as scaffolds for bone regeneration via characterization of their biocompatibility, porosity, mechanical properties, and water uptake behaviour. Biocompatibility of the scaffolds was assessed in direct-contact with the materials using normal human foetal osteoblast cell line. Cytotoxicity and osteoblast proliferation rate were evaluated. Porosity was assessed using computed microtomography analysis and mechanical properties were determined by compression testing. Obtained results demonstrated that chit/HA scaffold possessed significantly better mechanical properties (compressive strength: 1.23 MPa, Young's modulus: 0.46 MPa) than chit/glu/HA material (compressive strength: 0.26 MPa, Young's modulus: 0.25 MPa). However, addition of bacterial β-1,3-glucan to the chit/HA scaffold improved its flexibility and porosity. Moreover, chit/glu/HA scaffold revealed significantly higher water uptake capability (52.6% after 24 h of soaking) compared to the chit/HA (30.7%) and thus can serve as a very good drug delivery carrier. Chit/glu/HA scaffold was also more favourable to osteoblast survival (near 100% viability after 24-h culture), proliferation, and spreading compared to the chit/HA (63% viability). The chit/glu/HA possesses better biomedical potential than chit/HA scaffold. Nevertheless, poor mechanical properties of the chit/glu/HA limit its application to non-load bearing implantation area.
Graded/gradient Ti-6Al-4V mesh structures are fabricated by electron beam melting. The results of compressive properties indicate that the deformation behavior of these graded meshes is the weighted average of stress–strain response of each uniform mesh constituents. Through appropriate design of property and volume fraction of each constituents, graded/gradient meshes with high strength and energy absorption can be fabricated.
The cellular activity, biological response, and consequent integration of scaffold-cell construct in the physiological system are governed by the ability of cells to adhere, proliferate, and biomineralize. In this regard, we combine cellular biology and materials science and engineering to fundamentally elucidate the interplay between cellular activity and interconnected three-dimensional foamed architecture obtained by a novel process of electron beam melting and computational tools. Furthermore, the organization of key proteins, notably, actin, vinclulin, and fibronectin, involved in cellular activity and biological functions and relationship with the structure was explored. The interconnected foamed structure with ligaments was favorable to cellular activity that includes cell attachment, proliferation, and differentiation. The primary rationale for favorable modulation of cellular functions is that the foamed structure provided a channel for migration and communication between cells leading to highly mineralized extracellular matrix by the differentiating osteoblasts. The filopodial interaction amongst cells on the ligaments was a governing factor in the secretion of extracellular matrix, with consequent influence on maturation and mineralization.
We describe the structure of biodegradable chitosan-nanohydroxyapatite (nHA) composites scaffolds and their interaction with
pre-osteoblasts for bone tissue engineering. The scaffolds were fabricated via freezing and lyophilization. The nanocomposite
scaffolds were characterized by a highly porous structure and pore size of ∼50–125 μm, irrespective of nHA content. The observed
significant enhancement in the biological response of pre-osteoblast on nanocomposite scaffolds expressed in terms of cell
attachment, proliferation, and widespread morphology in relation to pure chitosan points toward their potential use as scaffold
material for bone regeneration.
We describe here the structure–property–process relationship of two sets of chitosan-based scaffolds as potential materials for hard tissue bioengineering applications. The first set of scaffolds was designed to study the effect of degree of deacetylation (%DD) of chitosan at 85 and 95% DD with identical molecular weight. The second set of scaffolds were synthesized to enhance the bioactivity and mechanical properties of 95% DD chitosan scaffold by the addition of 1, 3, and 5 wt% nanohydroxyapatite (nHA). Both sets of scaffolds were processed using freezing and lyophilization and their in vitro biological response was examined using pre-osteoblast (MC 3T3-E1) cells. The pure chitosan and chitosan–nHA nanocomposite scaffolds were characterized by a three-dimensional porous structure with pore size in the range of (≈50–120 µm), irrespective of %DD and nHA content. The compression modulus of hydrated 95% DD chitosan scaffolds increased from 6.0 kPa in pure chitosan to 9.2 kPa in chitosan-5 wt% nHA. The water uptake ability of 95% DD chitosan scaffolds was lower than 85% DD chitosan scaffolds, and decreased with the addition of nHA. On the other hand the water retention ability of 95% DD chitosan scaffolds was greater than 85% DD chitosan scaffolds but did not increase much with the addition of nHA. Chitosan degrades mainly by lysozyme present in physiological fluid. After 28 days of in vitro biodegradation test with physiological fluid, the 95% DD chitosan exhibited slightly lower degradation rate as compared to 85% DD and the degradation decreased with increase in nHA content in chitosan scaffold. Pre-osteoblasts (MC3T3-E1) grown on nHA scaffolds showed improved cell attachment, more proliferation, and a more extended cellular morphology. In vitro experimental observations suggest chitosan–nHA nanocomposite scaffolds as potential biomaterials for hard tissue bioengineering (bone regeneration) or as a template for cell attachment and proliferation in the repair of osseous and chondral defects.