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Wrist splint is a device for immobilising the wrist to facilitate the healing of wrist injury. However, conventional splint designing strategies lack consideration of biomechanical interaction with wrist joints, resulting in mechanical failure of splints or causing patient injuries. A novel design and optimisation method of customised functional wrist splints is needed clinically. In this study, we proposed a splint design method combining topology optimisation and additive manufacturing, based on the biomechanical analysis, to enable advanced customisation regarding functionality, comfort and ventilation. Three prototypes were fabricated via fused filament fabrication (FFF) horizontal printing, FFF vertical printing, and powder bed fusion (PBF). Finite element analysis was used to simulate the displacements of splints under the maximum loading provided by patients, with the results validated by physical tests. The stiffness and functionality of splints fabricated by different techniques were evaluated and compared. The results demonstrate that the developed splint is compatible with patients' functional and biomechanical needs, limiting 95.7% sagittal movement, 89.8% coronal movement, and 18.7% maximum grip strength. Moreover, among the three manufacturing methods, FFF vertical printing is recommended for general clinical use considering the safety, functionality, surface quality and cost.

Stress shielding secondary to bone resorption is one of the main causes of aseptic loosening, which limits the lifespan of hip prostheses and exacerbates revision surgery rates. In order to minimise post-hip replacement stress variations, this investigation proposes a low-stiffness, porous Ti6Al4V hip prosthesis, developed through selective laser melting (SLM). The stress shielding effect and potential bone resorption properties of the porous hip implant were investigated through both in vitro quasi-physiological experimental assays, together with finite element analysis. A solid hip implant was incorporated in this investigation for contrast, as a control group. The stiffness and fatigue properties of both the solid and the porous hip implants were measured through compression tests. The safety factor of the porous hip stem under both static and dynamic loading patterns was obtained through simulation. The porous hip implant was inserted into Sawbone/PMMA cement and was loaded to 2,300 N (compression). The proposed porous hip implant demonstrated a more natural stress distribution, with reduced stress shielding (by 70%) and loss in bone mass (by 60%), when compared to a fully solid hip implant. Solid and porous hip stems had a stiffness of 2.76 kN/mm and 2.15 kN/mm respectively. Considering all daily activities, the porous hip stem had a factor of safety greater than 2. At the 2,300 N load, maximum von Mises stresses on the hip stem were observed as 112 MPa on the medial neck and 290 MPa on the distal restriction point, whereby such values remained below the endurance limit of 3D printed Ti6Al4V (375 MPa). Overall, through the strut thickness optimisation process for a Ti6Al4V porous hip stem, stress shielding and bone resorption can be reduced, therefore proposing a potential replacement for the generic solid implant.

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.

Increasing concern about age-related diseases, particularly musculoskeletal injuries and orthopedic conditions, highlights the need for strategies such as tissue engineering to address them. Surface modification has been developed to create pro-healing interfaces, personalize scaffolds and provide novel medicines. Polydopamine, a mussel-inspired adhesive polymer with highly reactive functional groups that adhere to nearly all substrates, has gained attention in surface modification strategies for biomaterials. Polydopamine was primarily developed to modify surfaces, but its effectiveness has opened up promising approaches for further applications in bioengineering as carriers and nanoparticles. This review focuses on the recent discoveries of the role of polydopamine as a surface coating material, with focus on the properties that make it suitable for tackling musculoskeletal disorders. We report the evolution of using it in research, and discuss papers involving the progress of this field. The current research on the role of polydopamine in bone, cartilage, muscle, nerve, and tendon regeneration is discussed, thus giving comprehensive overview about the function of polydopamine both in-vitro and in-vivo. Finally, the report concludes presenting the critical challenges that must be addressed for the clinical translation of this biomaterial while exploring future perspectives and research opportunities in this area.

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. Translational 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.

Ti alloys with lattice structures are garnering more and more attention in the field of bone repair or regeneration due to their superior structural, mechanical, and biological properties. In this study, six types of composite lattice structures with different strut radius that consist of simple cubic (structure A), body-centered cubic (structure B), and edge-centered cubic (structure C) unit cells are designed. The designed structures are firstly simulated and analysed by the finite element (FE) method. Commercially pure Ti (CP–Ti) lattice structures with optimized unit cells and strut radius are then fabricated by selective laser melting (SLM), and the dimensions, microtopography, and mechanical properties are characterised. The results show that among the six types of composite lattice structures, combined BA, CA, and CB structures exhibit smaller maximum von-Mises stress, indicating that these structures have higher strength. Based on the fitting curves of stress/specific surface area versus strut radius, the optimized strut radius of BA, CA, and CB structures is 0.28, 0.23, and 0.30 mm respectively. Their corresponding compressive yield strength and compressive modulus are 42.28, 30.11, and 176.96 MPa, and 4.13, 2.16, and 7.84 GPa, respectively. The CP-Ti with CB unit structure presents a similar strength and compressive modulus to the cortical bone, which makes it a potential candidate for subchondral bone restorations.

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 Ti2Cu 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.

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.

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.

Osteochondral (OC) injuries are suffered by over 40 million patients in Europe alone. Tissue‐engineering approaches may provide a more promising alternative over current treatments by potentially eliminating the need for revision surgery and creating a long‐term substitute. Herein, the goal is to capture the natural biological and mechanical properties of the joint by developing a bilayer scaffold that is novel in two ways: first, a biomimetic bottom‐up approach is used to improve production precision and reduce immunogenicity; monomeric collagen type I and II are self‐assembled to fibrils and then processed to 3D scaffolds. Second, to induce a tissue‐specific response in mesenchymal stem cells (MSCs), polymerized chondroitin sulfate (PCS) is synthesized and grafted to collagen II and hydroxyapatite (HA) is added to collagen I. Incorporation of PCS into collagen II induces a chondrogenic response by upregulation of COL2A1 and ACAN expression, and incorporation of HA into collagen I stimulates osteogenesis and upregulates the expression of COL1A2 and RUNX2. It is remarkable that MSCs give rise to distinct behavior of chondrogenesis and osteogenesis in the two different regions of the bilayer scaffold. This hybrid scaffold of collagen II‐PCS and collagen I‐HA offers a great potential treatment for OC injuries.

For achieving early intervention treatment to help patients delay or avoid joint replacement surgery, a personalized scaffold should be designed coupling the effects of mechanical, fluid mechanical, chemical, and biological factors on tissue regeneration, which results in time- and cost-consuming trial-and-error analyses to investigate the in vivo test and related experimental tests. To optimize the fluid mechanical and material properties to predict osteogenesis and cartilage regeneration for the in vivo and clinical trial, a simulation approach is developed for scaffold design, which is composed of a volume of a fluid model for simulating the bone marrow filling process of the bone marrow and air, as well as a discrete phase model and a cell impingement model for tracking cell movement during bone marrow fillings. The bone marrow is treated as a non-Newtonian fluid, rather than a Newtonian fluid, because of its viscoelastic property. The simulation results indicated that the biofunctional bionic scaffold with a dense layer to prevent the bone marrow flow to the cartilage layer and synovia to flow into the trabecular bone area guarantee good osteogenesis and cartilage regeneration, which leads to high-accuracy in vivo tests in sheep . This approach not only predicts the final bioperformance of the scaffold but also could optimize the scaffold structure and materials by their biochemical, biological, and biomechanical properties.

Additive manufacturing has been used to develop a variety of scaffold designs for clinical and industrial applications. Mechanical properties (i.e., compression, tension, bending, and torsion response) of these scaffolds are significantly important for load-bearing orthopaedic implants. In this study, we designed and additively manufactured porous metallic biomaterials based on two different types of triply periodic minimal surface structures (i.e., gyroid and diamond) that mimic the mechanical properties of bone, such as porosity, stiffness, and strength. Physical and mechanical properties, including compressive, tensile, bending, and torsional stiffness and strength of the developed scaffolds, were then characterised experimentally and numerically using finite element method. Sheet thickness was constant at 300 μm, and the unit cell size was varied to generate different pore sizes and porosities. Gyroid scaffolds had a pore size in the range of 600–1200 μm and a porosity in the range of 54–72%, respectively. Corresponding values for the diamond were 900–1500 μm and 56–70%. Both structure types were validated experimentally, and a wide range of mechanical properties (including stiffness and yield strength) were predicted using the finite element method. The stiffness and strength of both structures are comparable to that of cortical bone, hence reducing the risks of scaffold failure. The results demonstrate that the developed scaffolds mimic the physical and mechanical properties of cortical bone and can be suitable for bone replacement and orthopaedic implants. However, an optimal design should be chosen based on specific performance requirements.

Titanium (Ti) and its alloys are attracting special attention in the field of dentistry and orthopedic bioengineering because of their mechanical adaptability and biological compatibility with the natural bone. The dental implant is subjected to masticatory forces in the oral environment and transfers these forces to the surrounding bone tissue. Therefore, by simulating the mechanical behavior of implants and surrounding bone tissue we can assess the effects of implants on bone growth quite accurately. In this study, dental implants with different gradient pore structures that consisted of simple cubic (structure a), body centered cubic (structure b) and side centered cubic (structure c) were designed, respectively. The strength of the designed gradient porous implant in the oral environment was simulated by three-dimensional finite element simulation technique to assess the mechanical adaptation by the stress-strain distribution within the surrounding bone tissue and by examining the fretting of the implant-bone interface. The results show that the maximum equivalent stress and strain in the surrounding bone tissue increase with the increase of porosity. The stress distribution of the gradient implant with a smaller difference between outer and inner pore structure is more uniform. So, a-b type porous implant exhibited less stress concentration. For a-b structure, when the porosity is between 40 and 47%, the stress and strain of bone tissue are in the range of normal growth. When subject to lingual and buccal stresses, an implant with higher porosity can achieve more uniform stress distribution in the surrounding cancellous bone than that of low porosity implant. Based on the simulated results, to achieve an improved mechanical fixation of the implant, the optimum gradient porous structure parameters should be: average porosity 46% with an inner porosity of 13% (b structure) and outer porosity of 59% (a structure), and outer pore sized 500 μm. With this optimized structure, the bone can achieve optimal ingrowth into the gradient porous structure, thus provide stable mechanical fixation of the implant. The maximum equivalent stress achieved 99 MPa, which is far below the simulation yield strength of 299 MPa.

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.

Cell attachment to a scaffold is a significant step toward successful tissue engineering. Cell seeding is the first stage of cell attachment, and its efficiency and distribution can affect the final biological performance of the scaffold. One of the contributing factors to maximize cell seeding efficiency and consequently cell attachment is the design of the scaffold. In this study, we investigated the optimum scaffold structure using two designs – truncated octahedron (TO) structure and cubic structure – for cell attachment. A simulation approach, by ANSYS Fluent coupling the volume of fluid (VOF) model, discrete phase model (DPM), and cell impingement model (CIM), was developed for cell seeding process in scaffold, and the results were validated with in vitro cell culture assays. Our observations suggest that both designs showed a gradual lateral variation of attached cells, and live cell movements are extremely slow by diffusion only while dead cells cannot move without external force. The simulation approaches supply a more accurate model to simulate cell adhesion for three-dimensional structures. As the initial stages of cell attachment in vivo are hard to observe, this novel method provides an opportunity to predict cell distribution, thereby helping to optimize scaffold structures. As tissue formation is highly related to cell distribution, this model may help researchers predict the effect of applied scaffold and reduce the number of animal testing.

Biofabrication has emerged as an attractive strategy to personalise medical care and provide new treatments for common organ damage or diseases. While it has made impactful headway in e.g., skin grafting, drug testing and cancer research purposes, its application to treat musculoskeletal tissue disorders in a clinical setting remains scarce. Albeit with several in vitro breakthroughs over the past decade, standard musculoskeletal treatments are still limited to palliative care or surgical interventions with limited long-term effects and biological functionality. To better understand this lack of translation, it is important to study connections between basic science challenges and developments with translational hurdles and evolving frameworks for this fully disruptive technology that is biofabrication. This review paper thus looks closely at the processing stage of biofabrication, specifically at the bioinks suitable for musculoskeletal tissue fabrication and their trends of usage. This includes underlying composite bioink strategies to address the shortfalls of sole biomaterials. We also review recent advances made to overcome long-standing challenges in the field of biofabrication, namely bioprinting of low-viscosity bioinks, controlled delivery of growth factors, and the fabrication of spatially graded biological and structural scaffolds to help biofabricate more clinically relevant constructs. We further explore the clinical application of biofabricated musculoskeletal structures, regulatory pathways, and challenges for clinical translation, while identifying the opportunities that currently lie closest to clinical translation. In this article, we consider the next era of biofabrication and the overarching challenges that need to be addressed to reach clinical relevance.

Osteochondral scaffold technology has emerged as a promising therapy for repairing osteochondral defects. Recent research suggests that seeding osteochondral scaffolds with bone marrow concentrate (BMC) may enhance tissue regeneration. To examine this hypothesis, this study examined subchondral bone regeneration in scaffolds with and without BMC. Ovine stifle condyle models were used for the in vivo study. Two scaffold systems (8 mm diameter and 10 mm thick) with and without BMC were implanted into the femoral condyle, and the tissues were retrieved after six months. The retrieved femoral condyles (with scaffold in) were examined using micro-computed tomography scans (micro-CT), and the micro-CT data were further analysed by ImageJ with respect to trabecular thickness, bone volume to total volume ratio (BV/TV) ratio, and degree of anisotropy of bone. Statistical analysis compared bone regeneration between scaffold groups and sub-set regions. These results were mostly insignificant (p < 0.05), with the exception of bone volume to total volume ratio when comparing scaffold composition and sub-set region. Additional trends in the data were observed. These results suggest that the scaffold composition and addition of BMC did not significantly affect bone regeneration in osteochondral defects after six months. However, this research provides data which may guide the development of future treatments.

Osteoarthritis (OA) is one of the most prevalent joint diseases, which causes pain and disability in the adult population. OA affects the osteochondral unit in the joints, which comprises both cartilage and subchondral bone. There has been some progress in understanding the changes in subchondral bone with progression of OA. However, local changes in subchondral bone such as microstructure or volumetric bone mineral density (vBMD) in connection with the defect in cartilage are relatively unexplored. To develop an effective treatment for progression of OA, it is important to understand how the physical environment provided by the subchondral bone affects the overlying cartilage. In this study, we examined the vBMD distribution in the OA joint tissues obtained from total hip replacement surgeries due to OA, using peripheral quantitative CT (pQCT). It was found that there is a significant decrease in vBMD, which co-localizes with the damage in the overlying cartilage. This was not limited to the subchondral bone immediately adjacent to the cartilage defect but continued in the layers below. Bone resorption and cyst formation in the OA tissues were also detected. We observed that the bone surrounding subchondral bone cysts exhibited much higher vBMD than that of the surrounding bones. pQCT was able to detect significant changes in vBMD between OA and non-OA samples, as well as between areas of different cartilage degeneration, which points to its potential as a technique for detection of early OA.

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.