Intrinsic Osteoinductivity of Porous Titanium Scaffold for Bone Tissue Engineering

Large bone defects and nonunions are serious complications that are caused by extensive trauma or tumour. As traditional therapies fail to repair these critical-sized defects, tissue engineering scaffolds can be used to regenerate the damaged tissue. Highly porous titanium scaffolds, produced by selective laser sintering with mechanical properties in range of trabecular bone (compressive strength 35 MPa and modulus 73 MPa), can be used in these orthopaedic applications, if a stable mechanical fixation is provided. Hydroxyapatite coatings are generally considered essential and/or beneficial for bone formation; however, debonding of the coatings is one of the main concerns. We hypothesised that the titanium scaffolds have an intrinsic potential to induce bone formation without the need for a hydroxyapatite coating. In this paper, titanium scaffolds coated with hydroxyapatite using electrochemical method were fabricated and osteoinductivity of coated and noncoated scaffolds was compared in vitro. Alizarin Red quantification confirmed osteogenesis independent of coating. Bone formation and ingrowth into the titanium scaffolds were evaluated in sheep stifle joints. The examinations after 3 months revealed 70% bone ingrowth into the scaffold confirming its osteoinductive capacity. It is shown that the developed titanium scaffold has an intrinsic capacity for bone formation and is a suitable scaffold for bone tissue engineering

Osteochondral scaffolds for early treatment of cartilage defects in osteoarthritic joints: from bench to clinic

Osteoarthritis is a degenerative joint disease, typified by the loss in the quality of cartilage and bone at the interface of a synovial joint, resulting in pain, stiffness and reduced mobility. The current surgical treatment for advanced stages of the disease is joint replacement, where the non-surgical therapeutic options or less invasive surgical treatments are no longer effective. These are major surgical procedures which have a substantial impact on patients’ quality of life and lifetime risk of requiring revision surgery. Treatments using regenerative methods such as tissue engineering methods have been established and are promising for the early treatment of cartilage degeneration in osteoarthritis joints. In this approach, 3-dimensional scaffolds (with or without cells) are employed to provide support for tissue growth. However, none of the currently available tissue engineering and regenerative medicine products promotes satisfactory durable regeneration of large cartilage defects. Herein, we discuss the current regenerative treatment options for cartilage and osteochondral (cartilage and underlying subchondral bone) defects in the articulating joints. We further identify the main hurdles in osteochondral scaffold development for achieving satisfactory and durable regeneration of osteochondral tissues. The evolution of the osteochondral scaffolds - from monophasic to multiphasic constructs - is overviewed and the osteochondral scaffolds that have progressed to clinical trials are examined with respect to their clinical performances and their potential impact on the clinical practices. Development of an osteochondral scaffold which bridges the gap between small defect treatment and joint replacement is still a grand challenge. Such scaffold could be used for early treatment of cartilage and osteochondral defects at early stage of osteoarthritis and could either negate or delay the need for joint replacements

Microcrystalline cellulose as filler in polycaprolactone matrices

Polycaprolactone is a biomaterial widely used for tissue engineering applications. However, its hydrophobicity hinders cell attachment and proliferation on its surface. In this study microcrystalline cellulose has been proposed as a functional filler for polycaprolactone matrices expected to improve these properties. Composite material samples containing 0, 2, 5, 10 and 20% w/w of microcrystalline cellulose have been manufactured by compression molding and evaluated in terms of their mechanical properties, swelling behavior, water contact angle values and sheep mesenchymal cells viability. The results confirm that the presence of the additive is able to increase the swelling ability of the material (the samples containing 20% w/w of additive are able to absorb an amount of water 6 times higher than the value for polycaprolactone ones), the Young’s modulus (from 224±14 MPa for polycaprolactone to 388±30 MPa for the composites containing 20% of microcrystalline cellulose) and the bioaffinity of polycaprolactone based composite materials

Eularian wall film model for predicting dynamic cell culture process to evaluate scaffold design in a perfusion bioreactor

In tissue engineering field, it is important to develop a suitable numerical model to evaluate scaffold geometry design. The experimental evaluation of the effect of each specific scaffold parameter on tissue regeneration requires large cost and long time expend. Dynamic cell culture is commonly used for generating tissues which could replace damaged tissues. A perfusion bioreactor model is developed which is able to simulate dynamic cell culture, to evaluate scaffold quality. The wall-film model is used to simulate cell attachment with the assumption that cells could be seen as liquid drops. In the process of cell attachment, the cells could impinge to a solid surface and form a liquid film which were considered as cell attached on the scaffold surface. Two types of cell-scaffold interactions were involved in numerical models including trap model and Stanton-Rutland (Cell impinge model—CIM) model. For trap model, all cells impinged the scaffold are seen as attached. For Stanton-Rutland model, four regimes of cell-scaffold interaction are involved in the cell attachment, including stick, rebound, spread, and splash, and only stick and spread are seen as attached. By comparison with two different numerical methods, the results showed that CIM model result is more related to the experimental results than trap model, which indicated that four regimes of cell-scaffold interaction occurred in cell attachment process. By evaluating two different geometry scaffold's cells seeding by these two models, the results further indicated that this model are able to use for assessing the scaffold design

Synergistic interactions between wear and corrosion of Ti-16Mo orthopedic alloy

In this study, corrosion, wear, and tribocorrosion of Ti-16Mo alloy manufactured by powder metallurgy (PM) in phosphate-buffered saline are investigated. The results indicate that the corrosion rate of Ti-16Mo alloy increases about 100 times from 0.00009 mm/yr to 0.00851 mm/yr under the tribocorrosion condition. Also, corrosion accelerates wear loss, and wear increment rate due to the corrosion (4.7715 mm/yr) of Ti-16Mo alloy is about 40% of pure mechanical wear rate (11.78 mm/yr). Compared with as-cast pure Ti (23.70999 mm/yr) and Ti-6Al-4 V (17.12003 mm/yr), Ti-16Mo alloy exhibits the lowest materials loss of 16.56001 mm/yr making it become a promising alloy for bone-tissue applications

Characteristics of novel Ti–10Mo-xCu alloy by powder metallurgy for potential biomedical implant applications

When biomaterials are implanted in the human body, the surfaces of the implants become favorable sites for microbial adhesion and biofilm formation, causing peri-implant infection which frequently results in the failure of prosthetics and revision surgery. Ti–Mo alloy is one of the commonly used implant materials for load-bearing bone replacement, and the prevention of infection of Ti–Mo implants is therefore crucial. In this study, bacterial inhibitory copper (Cu) was added to Ti–Mo matrix to develop a novel Ti–Mo–Cu alloy with bacterial inhibitory property. The effects of Cu content on microstructure, tensile properties, cytocompatibility, and bacterial inhibitory ability of Ti–Mo–Cu alloy were systematically investigated. Results revealed that Ti–10Mo–1Cu alloy consisted of α and β phases, while there were a few Ti_{2}Cu intermetallic compounds existed for Ti–10Mo–3Cu and Ti–10Mo–5Cu alloys, in addition to α and β phases. The tensile strength of Ti–10Mo-xCu alloy increased with Cu content while elongation decreased. Ti–10Mo–3Cu alloy exhibited an optimal tensile strength of 1098.1 MPa and elongation of 5.2%. Cytocompatibility study indicated that none of the Ti–10Mo-xCu alloys had a negative effect on MC3T3-E1 cell proliferation. Bacterial inhibitory rates against S. aureus and E. coli increased with the increase in Cu content of Ti–10Mo-xCu alloy, within the ranges of 20–60% and 15–50%, respectively. Taken together, this study suggests that Ti–10Mo–3Cu alloy with high strength, acceptable elongation, excellent cytocompatibility, and the bacterial inhibitory property is a promising candidate for biomedical implant applications

Nano-Modified Titanium Implant Materials: A Way Toward Improved Antibacterial Properties

Titanium and its alloys have superb biocompatibility, low elastic modulus, and favorable corrosion resistance. These exceptional properties lead to its wide use as a medical implant material. Titanium itself does not have antibacterial properties, so bacteria can gather and adhere to its surface resulting in infection issues. The infection is among the main reasons for implant failure in orthopedic surgeries. Nano-modification, as one of the good options, has the potential to induce different degrees of antibacterial effect on the surface of implant materials. At the same time, the nano-modification procedure and the produced nanostructures should not adversely affect the osteogenic activity, and it should simultaneously lead to favorable antibacterial properties on the surface of the implant. This article scrutinizes and deals with the surface nano-modification of titanium implant materials from three aspects: nanostructures formation procedures, nanomaterials loading, and nano-morphology. In this regard, the research progress on the antibacterial properties of various surface nano-modification of titanium implant materials and the related procedures are introduced, and the new trends will be discussed in order to improve the related materials and methods

Stress shielding and bone resorption of press-fit polyether-ether-ketone (PEEK) hip prosthesis: a sawbone model study

Stress shielding secondary to bone resorption is one of the main causes of aseptic loosening, which limits the lifespan of the hip prostheses and increases the rates of revision surgery. This study proposes a low stiffness polyether-ether-ketone (PEEK) hip prostheses, produced by fused deposition modelling to minimize the stress difference after the hip replacement. The stress shielding effect and the potential bone resorption of the PEEK implant was investigated through both experimental tests and FE simulation. A generic Ti6Al4V implant was incorporated in this study to allow fair comparison as control group. Attributed to the low stiffness, the proposed PEEK implant showed a more natural stress distribution, less stress shielding (by 104%), and loss in bone mass (by 72%) compared with the Ti6Al4V implant. The stiffness of the Ti6Al4V and the PEEK implant were measured through compression tests to be 2.76 kN/mm and 0.276 kN/mm. The factor of safety for the PEEK implant in both static and dynamic loading scenarios were obtained through simulation. Most of the regions in the PEEK implant were tested to be safe (FoS larger than 1) in terms of representing daily activities (2300 N), while the medial neck and distal restriction point of the implant attracts large von Mises stress 82 MPa and 76 MPa, respectively, and, thus, may possibly fail during intensive activities by yield and fatigue. Overall, considering the reduction in stress shielding and bone resorption in cortical bone, PEEK could be a promising material for the patient-specific femoral implants

Sheep condyle model evaluation of bone marrow cell concentrate combined with a scaffold for repair of large osteochondral defects

AIMS: Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone. METHODS: The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety. RESULTS: The results six months postoperatively showed that there were no significant differences in bone regrowth and mineral density between BMC-treated animals and controls. A significant upregulation of messenger RNA (mRNA) for types I and II collagens in the BMC group was observed, but there were no differences in the formation of hyaline-like cartilage between the groups. A trend towards reduced sulphated glycosaminoglycans (sGAG) breakdown was detected in the BMC group but this was not statistically significant. Functional weightbearing was not affected by the inclusion of BMC. CONCLUSION: Our results indicated that the addition of BMC to scaffold is safe and has some potentially beneficial effects on osteochondral-tissue regeneration, but not on the functional endpoint of orthopaedic interest. Cite this article: Bone Joint Res 2021;10(10):677-689

Bilayered scaffold with 3D printed stiff subchondral bony compartment to provide constant mechanical support for long-term cartilage regeneration

BACKGROUND/OBJECTIVE: We seek to figure out the effect of stable and powerful mechanical microenvironment provided by Ti alloy as a part of subchondral bone scaffold on long-term cartilage regeneration. METHODS: we developed a bilayered osteochondral scaffold based on the assumption that a stiff subchondral bony compartment would provide stable mechanical support for cartilage regeneration and enhance subchondral bone regeneration. The subchondral bony compartment was prepared from 3D printed Ti alloy, and the cartilage compartment was created from a freeze-dried collagen sponge, which was reinforced by poly-lactic-co-glycolic acid (PLGA). RESULTS: In vitro evaluations confirmed the biocompatibility of the scaffold materials, while in vivo evaluations demonstrated that the mechanical support provided by 3D printed Ti alloy layer plays an important role in the long-term regeneration of cartilage by accelerating osteochondral formation and its integration with the adjacent host tissue in osteochondral defect model at rabbit femoral trochlea after 24 weeks. CONCLUSION: Mechanical support provided by 3D printing Ti alloy promotes cartilage regeneration by promoting subchondral bone regeneration and providing mechanical support platform for cartilage synergistically. TRANSITIONAL POTENTIAL STATEMENT: The raw materials used in our double-layer osteochondral scaffolds are all FDA approved materials for clinical use. 3D printed titanium alloy scaffolds can promote bone regeneration and provide mechanical support for cartilage regeneration, which is very suitable for clinical scenes of osteochondral defects. In fact, we are conducting clinical trials based on our scaffolds. We believe that in the near future, the scaffold we designed and developed can be formally applied in clinical practice