Bony ingrowth potential of 3D-printed porous titanium alloy: a direct comparison of interbody cage materials in an in vivo ovine lumbar fusion model.

Background contextThere is significant variability in the materials commonly used for interbody cages in spine surgery. It is theorized that three-dimensional (3D)-printed interbody cages using porous titanium material can provide more consistent bone ingrowth and biological fixation.PurposeThe purpose of this study was to provide an evidence-based approach to decision-making regarding interbody materials for spinal fusion.Study designA comparative animal study was performed.MethodsA skeletally mature ovine lumbar fusion model was used for this study. Interbody fusions were performed at L2-L3 and L4-L5 in 27 mature sheep using three different interbody cages (ie, polyetheretherketone [PEEK], plasma sprayed porous titanium-coated PEEK [PSP], and 3D-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 (µ-CT); 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.ResultsFlexion-extension range of motion (ROM) was statistically reduced for the PTA group compared with the PEEK cages at 16 weeks (p-value=.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≤.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 with the PEEK cages (p-value<.01).ConclusionsA direct comparison of interbody implants demonstrates significant and measurable differences in biomechanical, µ-CT, and histologic performance in an ovine model. The 3D-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 with PEEK and PSP

Applications of 3D printing in the management of severe spinal conditions

The latest and fastest-growing innovation in the medical field has been the advent of three-dimensional printing technol- ogies, which have recently seen applications in the production of low-cost, patient-specific medical implants. While a wide range of three-dimensional printing systems has been explored in manufacturing anatomical models and devices for the medical setting, their applications are cutting-edge in the field of spinal surgery. This review aims to provide a com- prehensive overview and classification of the current applications of three-dimensional printing technologies in spine care. Although three-dimensional printing technology has been widely used for the construction of patient-specific ana- tomical models of the spine and intraoperative guide templates to provide personalized surgical planning and increase pedicle screw placement accuracy, only few studies have been focused on the manufacturing of spinal implants. Therefore, three-dimensional printed custom-designed intervertebral fusion devices, artificial vertebral bodies and disc substitutes for total disc replacement, along with tissue engineering strategies focused on scaffold constructs for bone and cartilage regeneration, represent a set of promising applications towards the trend of individualized patient care

Human lumbar spine biomechanics: study of pathologies and new surgical procedures

This thesis aims to shed light on the process that undergoes the lumbar spine as a result of intervertebral disc degeneration and different lumbar surgeries, paying special attention on the main risk factors and how to overcome them. Low back pain is the leading musculoskeletal disorder in all developed countries generating high medical related costs. Intervertebral disc degeneration is one of the most common causes of low back pain. When conservative treatments fail to relieve this pain, lumbar surgery is needed and, in this regard, lumbar fusion is the \textquotedblleft gold standard\textquotedblright technique to provide stability and neural decompression.Degenerative disc disease has been studied through two different approaches. An in-vivo animal model was reproduced and followed-up with MRI and mechanical testing to see how the water content decreased while the stiffness of the tissue increased. Then, degeneration was induced in a single disc of the human lumbar spine and the effects on the adjacent disc were investigated by the use of the finite element models. Further on, different procedures for segmental fusion were computationally simulated. A comparison among different intersomatic cage designs, supplemented with posterior screw fixation or placed in a stand-alone fashion, showed how the supplementary fixation drastically decreased the motion in the affected segment increasing the risk of adjacent segment disease more than a single placed cage. However, one of the main concerns regarding the use of cages without additional fixation is the subsidence of the device into the vertebral bone. A parametric study of the cage features and placement pointed to the width, curvature, and position as the most influential parameters for stability and subsidence.Finally, two different algorithms for tissue healing were implemented and applied for the first time to predict lumbar fusion in 3D models. The self-repairing ability of the bone was tested after simple nucleotomy and after instrumentation with internal fixation, anterior plate or stand-alone intersomatic cage predicting, in agreement with previous animal and clinical studies, that instrumentation may be not necessary to promote segmental fusion. In particular, the intervertebral disc height was seen to play an important role in the bone bridge or osteophyte formation.To summarize, this thesis has focused in the main controversial issues of intervertebral disc degeneration and lumbar fusion, such as degenerative process, adjacent segment disease, segment stability, cage subsidence or bone bridging. All the models described in this thesis could serve as a powerful tool for the pre-clinical evaluation of patient-specific surgical outcomes supporting clinician decisions. This thesis aims to shed light on the process that undergoes the lumbar spine as a result of intervertebral disc degeneration and different lumbar surgeries, paying special attention on the main risk factors and how to overcome them. Low back pain is the leading musculoskeletal disorder in all developed countries generating high medical related costs. Intervertebral disc degeneration is one of the most common causes of low back pain. When conservative treatments fail to relieve this pain, lumbar surgery is needed and, in this regard, lumbar fusion is the \textquotedblleft gold standard\textquotedblright technique to provide stability and neural decompression. Degenerative disc disease has been studied through two different approaches. An in-vivo animal model was reproduced and followed-up with MRI and mechanical testing to see how the water content decreased while the stiffness of the tissue increased. Then, degeneration was induced in a single disc of the human lumbar spine and the effects on the adjacent disc were investigated by the use of the finite element models. Further on, different procedures for segmental fusion were computationally simulated. A comparison among different intersomatic cage designs, supplemented with posterior screw fixation or placed in a stand-alone fashion, showed how the supplementary fixation drastically decreased the motion in the affected segment increasing the risk of adjacent segment disease more than a single placed cage. However, one of the main concerns regarding the use of cages without additional fixation is the subsidence of the device into the vertebral bone. A parametric study of the cage features and placement pointed to the width, curvature, and position as the most influential parameters for stability and subsidence. Finally, two different algorithms for tissue healing were implemented and applied for the first time to predict lumbar fusion in 3D models. The self-repairing ability of the bone was tested after simple nucleotomy and after instrumentation with internal fixation, anterior plate or stand-alone intersomatic cage predicting, in agreement with previous animal and clinical studies, that instrumentation may be not necessary to promote segmental fusion. In particular, the intervertebral disc height was seen to play an important role in the bone bridge or osteophyte formation. To summarize, this thesis has focused in the main controversial issues of intervertebral disc degeneration and lumbar fusion, such as degenerative process, adjacent segment disease, segment stability, cage subsidence or bone bridging. All the models described in this thesis could serve as a powerful tool for the pre-clinical evaluation of patient-specific surgical outcomes supporting clinician decisions. <br /

Studies on Spinal Fusion from Computational Modelling to ‘Smart’ Implants

Low back pain, the worldwide leading cause of disability, is commonly treated with lumbar interbody fusion surgery to address degeneration, instability, deformity, and trauma of the spine. Following fusion surgery, nearly 20% experience complications requiring reoperation while 1 in 3 do not experience a meaningful improvement in pain. Implant subsidence and pseudarthrosis in particular present a multifaceted challenge in the management of a patient’s painful symptoms. Given the diversity of fusion approaches, materials, and instrumentation, further inputs are required across the treatment spectrum to prevent and manage complications. This thesis comprises biomechanical studies on lumbar spinal fusion that provide new insights into spinal fusion surgery from preoperative planning to postoperative monitoring. A computational model, using the finite element method, is developed to quantify the biomechanical impact of temporal ossification on the spine, examining how the fusion mass stiffness affects loads on the implant and subsequent subsidence risk, while bony growth into the endplates affects load-distribution among the surrounding spinal structures. The computational modelling approach is extended to provide biomechanical inputs to surgical decisions regarding posterior fixation. Where a patient is not clinically pre-disposed to subsidence or pseudarthrosis, the results suggest unilateral fixation is a more economical choice than bilateral fixation to stabilise the joint. While finite element modelling can inform pre-surgical planning, effective postoperative monitoring currently remains a clinical challenge. Periodic radiological follow-up to assess bony fusion is subjective and unreliable. This thesis describes the development of a ‘smart’ interbody cage capable of taking direct measurements from the implant for monitoring fusion progression and complication risk. Biomechanical testing of the ‘smart’ implant demonstrated its ability to distinguish between graft and endplate stiffness states. The device is prepared for wireless actualisation by investigating sensor optimisation and telemetry. The results show that near-field communication is a feasible approach for wireless power and data transfer in this setting, notwithstanding further architectural optimisation required, while a combination of strain and pressure sensors will be more mechanically and clinically informative. Further work in computational modelling of the spine and ‘smart’ implants will enable personalised healthcare for low back pain, and the results presented in this thesis are a step in this direction

Biodegradable Polymers in Bone Tissue Engineering

The use ofdegradable polymers in medicine largely started around the mid 20th century with their initial use as in vivo resorbing sutures. Thorough knowledge on this topic as been gained since then and the potential applications for these polymers were, and still are, rapidly expanding. After improving the properties of lactic acid-based polymers, these were no longer studied only from a scientific point of view, but also for their use in bone surgery in the 1990s. Unfortunately, after implanting these polymers, different foreign body reactions ranging from the presence of white blood cells to sterile sinuses with resorption of the original tissue were observed. This led to the misconception that degradable polymers would, in all cases, lead to inflammation and/or osteolysis at the implantation site. Nowadays, we have accumulated substantial knowledge on the issue of biocompatibility of biodegradable polymers and are able to tailor these polymers for specific applications and thereby strongly reduce the occurrence of adverse tissue reactions. However, the major issue of biofunctionality, when mechanical adaptation is taken into account, has hitherto been largely unrecognized. A thorough understanding of how to improve the biofunctionality, comprising biomechanical stability, but also visualization and sterilization of the material, together with the avoidance of fibrotic tissue formation and foreign body reactions, may greatly enhance the applicability and safety of degradable polymers in a wide area of tissue engineering applications. This review will address our current understanding of these biofunctionality factors, and will subsequently discuss the pitfalls remaining and potential solutions to solve these problems

Scaffold Translation: Barriers Between Concept and Clinic

Translation of scaffold-based bone tissue engineering (BTE) therapies to clinical use remains, bluntly, a failure. This dearth of translated tissue engineering therapies (including scaffolds) remains despite 25 years of research, research funding totaling hundreds of millions of dollars, over 12,000 papers on BTE and over 2000 papers on BTE scaffolds alone in the past 10 years (PubMed search). Enabling scaffold translation requires first an understanding of the challenges, and second, addressing the complete range of these challenges. There are the obvious technical challenges of designing, manufacturing, and functionalizing scaffolds to fill the Form, Fixation, Function, and Formation needs of bone defect repair. However, these technical solutions should be targeted to specific clinical indications (e.g., mandibular defects, spine fusion, long bone defects, etc.). Further, technical solutions should also address business challenges, including the need to obtain regulatory approval, meet specific market needs, and obtain private investment to develop products, again for specific clinical indications. Finally, these business and technical challenges present a much different model than the typical research paradigm, presenting the field with philosophical challenges in terms of publishing and funding priorities that should be addressed as well. In this article, we review in detail the technical, business, and philosophical barriers of translating scaffolds from Concept to Clinic. We argue that envisioning and engineering scaffolds as modular systems with a sliding scale of complexity offers the best path to addressing these translational challenges.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90495/1/ten-2Eteb-2E2011-2E0251.pd

Effects of surface chemistry and surface topography on polyether-ether-ketone osseointegration

Osseointegration of a novel porous polymer material made from polyether-ether-ketone (PEEK) was investigated using in vitro cell models and in vivo small animal models. Porous PEEK was compared to conventional smooth PEEK surfaces and plasma-sprayed titanium coated PEEK surfaces. The relative effects of surface material and surface topography were also investigated utilizing nano-scale atomic layer deposition (ALD) coatings. Histological, micro-computed tomography and biomechanical outcomes support that the porous PEEK material facilitated bone ingrowth and implant fixation compared to other surfaces. These results could provide valuable insight for the development of more effective devices for spinal fusions and other orthopaedic applications.Ph.D

BIOLIF: Artrodese lombar intersomática - abordagem não instrumentada

Tese de doutoramento em MedicinaSpinal fusion (SF) is a surgical procedure conducted to promote bone growth in-between spinal segments, supported by fixation hardware, and complemented by bone graft or bone substitute. There are recognized risks and complications associated with instrumentation, such as damage to surrounding tissues, neurological deficits, material failure or migration and non-union. In this thesis, a novel approach is proposed based on the development of an adhesive, biodegradable and injectable foam, with the purpose to avoid instrumentation in SF. Carbon dioxide foaming was explored as processing methodology to generate, within physiologically compatible conditions, polycaprolactone (PCL) foams with morphological characteristics equivalent to those found in trabecular bone. A three-dimensional, mechanically stable and bioactive composite of PCL+βTCP+Dexamethasone was foamed at 45ºC and 5 MPa. This optimized PCL processing opened the possibility for creating a porous foam, delivered directly into the intervertebral space through a surgical tool designed and built for this purpose. The adhesive properties of PCL were further improved through modification with polydopamine (pDA) and polymethacrylic acid (pMAA). After tensile testing, PCL pDA pMAA material–bone interface remained intact at both ends (adhesivity significantly superior to non-modified PCL, p<0.05). Further in vitro assays confirmed the formulation as non-cytotoxic and bioactive (calcium phosphate (CaP) layer formation). Lastly, the surgical feasibility of PCL pDA pMAA foaming and its biological performance for non instrumented spinal fusion were assessed in a 6-month survival study using an interbody fusion porcine model. Segmental instrumented arthrodesis was used as control group. Minimally invasive in situ foaming of PCL pDA pMAA (BIOLIF) was technically achieved, leading to reduced surgical time (p<0.05) as compared to instrumentation. Animals in BIOLIF approach demonstrated no surgical complications and a higher mobility (p<0.05) at immediate post-op. Spinal fusion was determined by a set of assessments including: i) bone volume/ tissue volume percentage (BV/TV), superior in BIOLIF group (p<0.05); ii) reduced range of motion and increased stiffness of the treated spinal segment, equivalent in both groups; and iii) a relatively well-organized newly formed osseous structure identified by histological analysis at BIOLIF samples. As conclusion, the results obtained in this work could open a new perspective for lumbar instrumentation-free spinal fusion using biologic solutions.A artrodese da coluna vertebral é um procedimento cirúrgico que visa a indução de crescimento ósseo entre segmentos vertebrais, utilizando sistemas de fixação e suplementação com enxerto ósseo ou substituto sintético. São reconhecidos riscos e complicações associados à instrumentação, incluindo, danos nos tecidos circundantes, compromisso neurológico, risco de mobilização ou migração do material e pseudartrose. Nesta tese, é proposta uma nova abordagem, baseada no desenvolvimento de uma espuma adesiva, biodegradável e injetável, de forma de realizar artrodese intersomática lombar sem recurso a instrumentação. A tecnologia supercrítica/subcrítica foi explorada para a produção de uma espuma de policaprolactona (PCL), em condições fisiologicamente compatíveis, com características morfológicas equivalentes às encontradas no osso trabecular. Foi possível obter a 45ºC e 5 MPa, uma estrutura tridimensional de PCL+βTCP+Dexametasona mecanicamente estável e com propriedades bioativas. Estas condições tornaram possível a extrusão da espuma diretamente no espaço intersomático, através de um instrumento cirúrgico desenvolvido para esse efeito. As propriedades adesivas do PCL foram otimizadas através da modificação do polímero com polidopamina (pDA) e ácido polimetacrílico (pMAA), que se demonstrou significativamente mais adesivo do que o PCL p<0,05 em ensaios mecânicos de tração. As propriedades citocompatíveis e bioativas da formulação foram confirmadas em ensaios in vitro. Por fim, a exequibilidade cirúrgica da extrusão da espuma de PCL pDA pMAA, e o seu desempenho biológico, foram avaliados num estudo de sobrevida de 6 meses usando o porco doméstico como modelo animal. Como grupo de controlo foi realizada artrodese intersomática instrumentada. Foi tecnicamente possível efetuar extrusão in situ de PCL pDA pMAA (BIOLIF) por via minimamente invasiva, sendo o tempo de procedimento cirúrgico significativamente inferior (p<0,05) ao grupo da instrumentação. Os animais do grupo BIOLIF não demonstraram complicações cirúrgicas e apresentaram uma maior mobilidade (p<0,05) no pós-operatório imediato. A qualidade da artrodese foi avaliada por um conjunto de parâmetros: i) a relação volume ósseo/ volume total (BV/TV), superior no grupo BIOLIF (p<0,05); ii) a redução da amplitude de movimento e o aumento da rigidez do segmento vertebral intervencionado, equivalente em ambos os grupos; e iii) uma estrutura óssea recém-formada relativamente bem-organizada no grupo BIOLIF, identificada por análise histológica. Em conclusão, os resultados obtidos neste trabalho podem abrir uma nova perspectiva para a utilização de soluções biológicas como forma de realizar artrodese intersomática lombar sem recurso a instrumentação.Portuguese Foundation for Science and Technology (FCT) - projects UIDB/50026/2020 and UIDP/50026/2020

Complex geometry and integrated macro-porosity: Clinical applications of electron beam melting to fabricate bespoke bone-anchored implants

The last decade has witnessed rapid advancements in manufacturing technologies for biomedical implants. Additive manufacturing (or 3D printing) has broken down major barriers in the way of producing complex 3D geometries. Electron beam melting (EBM) is one such 3D printing process applicable to metals and alloys. EBM offers build rates up to two orders of magnitude greater than comparable laser-based technologies and a high vacuum environment to prevent accumulation of trace elements. These features make EBM particularly advantageous for materials susceptible to spontaneous oxidation and nitrogen pick-up when exposed to air (e.g., titanium and titanium-based alloys). For skeletal reconstruction(s), anatomical mimickry and integrated macro-porous architecture to facilitate bone ingrowth are undoubtedly the key features of EBM manufactured implants. Using finite element modelling of physiological loading conditions, the design of a prosthesis may be further personalised. This review looks at the many unique clinical applications of EBM in skeletal repair and the ground-breaking innovations in prosthetic rehabilitation. From a simple acetabular cup to the fifth toe, from the hand-wrist complex to the shoulder, and from vertebral replacement to cranio-maxillofacial reconstruction, EBM has experienced it all. While sternocostal reconstructions might be rare, the repair of long bones using EBM manufactured implants is becoming exceedingly frequent. Despite the various merits, several challenges remain yet untackled. Nevertheless, with the capability to produce osseointegrating implants of any conceivable shape/size, and permissive of bone ingrowth and functional loading, EBM can pave the way for numerous fascinating and novel applications in skeletal repair, regeneration, and rehabilitation. Statement of significance: Electron beam melting (EBM) offers unparalleled possibilities in producing contaminant-free, complex and intricate geometries from alloys of biomedical interest, including Ti6Al4V and CoCr. We review the diverse range of clinical applications of EBM in skeletal repair, both as mass produced off-the-shelf implants and personalised, patient-specific prostheses. From replacing large volumes of disease-affected bone to complex, multi-material reconstructions, almost every part of the human skeleton has been replaced with an EBM manufactured analog to achieve macroscopic anatomical-mimickry. However, various questions regarding long-term performance of patient-specific implants remain unaddressed. Directions for further development include designing personalised implants and prostheses based on simulated loading conditions and accounting for trabecular bone microstructure with respect to physiological factors such as patient\u27s age and disease status