In a tissue-engineered bone scaffold implant, the process of neo-tissue ingrowth and remodelling into hard lamellar bone occurs slowly; it typically requires a period of several months to a year (or more) to complete. This research considers the design optimisation of a scaffold's unit cell geometry for the purpose of accelerating the rate at which neo-tissue forms in the porous network of the scaffold (ingrowth), and hence, reduce the length of time to complete the bone ingrowth process. In this study, the basic structure of the scaffold is the Schwarz Primitive (P) surface unit cell, selected for its compelling biomechanical and permeability characteristics. The geometry of the scaffold is varied using two parameters (namely iso-value, k, and spatial period, a) within the surface equation defining the Schwarz P-surface unit cell. In total, sixteen different unit cell geometries are considered here with the porosity ranging from 50% to 82%. The design objectives for the scaffold are to (i) enhance mechanobiological stimulus conditions conducive to bone apposition and (ii) enhance permeability to improve the transport of nutrients/oxygen and metabolities to and from the sites of neo-tissue formation throughout the porous scaffold. The independent design variables (k and a) of the periodic unit cell geometry are optimised to best satisfy the design objectives of appositional mechanobiological stimulus and biotransporting permeability. First, a reconstructed sheep mandible computed tomographic (CT)-based finite element (FE) analysis model is used to relate the strain energy density and mechanobiological stimulus to the design variables. Next, a computational fluid dynamics (CFD) model of a 5 × 5 × 5 unit cell scaffold is developed to relate the distributions of pressure and fluid velocity to the design variables. Then, surrogate modelling is undertaken in which bivariate cubic polynomial response surfaces are fitted to the FE and CFD analysis output data to form mathematical functions of each objective with respect to the two design variables. Finally, a multiobjective optimisation algorithm is invoked to determine the best trade-off between the competing design objectives of mechanobiological stimulus and biofluidic permeability. The novel design of the scaffold structure is anticipated to provide a better biomechanical and biotransport environment for tissue regeneration.

In recent years, 3D printing has become a rapidly developing manufacturing technology with huge potential and is influencing many industries, such as engineering, art, education, medicine, aerospace, and many more. Of the many technologies, the one used most frequently is the FDM (fused deposition modeling) method, which is widely available, relatively simple and inexpensive. The essence of this method is to extrude a thermoplastic material through a heated nozzle in a controlled manner. PLA, or polylactide, is a naturally sourced material with good biodegradable properties. It is frequently used in 3D printing and is derived from natural ingredients such as maize starch or sugar cane. The current study aimed to determine the effects of adding plant-origin food industry by-products, such as carrot pomace and ground walnut shells, to PLA on the mechanical and biodegradable properties of specimens printed using the FDM technology. The assumed research objective is consistent with the issue of sustainable development in the management of by-products from the food industry. The study used a pulverized fraction of each additive, with a particle size of less than 0.2 mm, which was introduced into the base material PLA at rates of 1%, 3% and 5%. The mixtures prepared in this manner were used to print (using FDM technology) standardized specimens, which were assessed for strength (bending and breaking tests) and biodegradability (weight loss after 60 and 120 days of storage under varying climatic conditions). It was observed that the additive increased the bending strength parameters (by a maximum of 44.9%, as compared to the raw material with no additives) while decreasing the breaking stress (by a maximum of approximately 15%, as compared to the raw material with no additives). Using plant additives increased biodegradability (up to 7.6%) compared to the control material.

The triply periodic minimal surface (TPMS) Gyroid porous scaffolds were built with identical porosity while varying pore sizes were used by fluid mechanics finite element analysis (FEA) to simulate the in vivo microenvironment. The effects of scaffolds with different pore sizes on cell adhesion, proliferation, and osteogenic differentiation were evaluated through calculating fluid velocity, wall shear stress, and permeability in the scaffolds.

Three types of gyroid porous scaffolds, with pore sizes of 400, 600 and 800 μm, were established by nTopology software. Each scaffold had dimensions of 10 mm × 10 mm × 10 mm and isotropic internal structures. The models were imported to the ANSYS 2022R1 software, and meshed into over 3 million unstructured tetrahedral elements. Boun- dary conditions were set with inlet flow velocities of 0.01, 0.1, and 1 mm/s, and outlet pressure of 0 Pa. Pressure, velocity, and wall shear stress were calculated as fluid flowed through the scaffolds using the Navier-Stokes equations. At the same time, permeability was determined based on Darcy' s law. The compressive strength of scaffolds with different pore sizes was evaluated by ANSYS 2022R1 Static structural analysis.

A linear relationship was observed between the wall shear stress and fluid velocity at inlet flow rates of 0.01, 0.1 and 1 mm/s, with increasing velocity leading to higher wall shear stress. At the flow velocity of 0.1 mm/s, the initial pressures of scaffolds with pore sizes of 400, 600 and 800 μm were 0.272, 0.083 and 0.079 Pa, respectively. The fluid pressures were gradually decreased across the scaffolds. The average flow velocities were 0.093, 0.078 and 0.070 mm/s, the average wall shear stresses 2.955, 1.343 and 1.706 mPa, permeabilities values 0.54×10-8 1.80×10-8 and 1.89×10-8 m2 in the scaffolds with pore sizes of 400, 600 and 800 μm. The scaffold surface area proportions according with optimal wall shear stress range for cell growth and osteogenic differentiation were calcula-ted, which was highest in the 600 μm scaffold (27.65%), followed by the 800 μm scaffold (17.30%) and the 400 μm scaffold (1.95%). The compressive strengths of the scaffolds were 23, 26 and 34 MPa for the 400, 600 and 800 μm pore sizes.

The uniform stress distributions appeared in all gyroid scaffold types under compressive stress. The permeabilities of scaffolds with pore sizes of 600 and 800 μm were significantly higher than the 400 μm. The average wall shear stress in the scaffold of 600 μm was the lowest, and the scaffold surface area proportion for cell growth and osteogenic differentiation the largest, indicating that it might be the most favorable design for supporting these cellular activities.

Dental implantology has evolved significantly since the introduction of additive manufacturing, which allows for the reproduction of natural bone's porous architecture to improve bone tissue compatibility and address stress distribution issues important to long-term implant success. Conventional solid dental implants frequently cause stress shielding, which compromises osseointegration and reduces durability.

The current research proposes to examine the biomechanical efficacy of fully and hybrid gyroid triply periodic minimum surface (TPMS) latticed implants across different cell sizes to optimize stress distribution and improve implant durability.

This study evaluates six fully and hybrid gyroid (TPMS) latticed implants, including fully latticed designs with three cell sizes-FLI_111 (1 mm × 1 mm × 1 mm), FLI_222 (2 mm × 2 mm × 2 mm), and FLI_333 (3 mm × 3 mm × 3 mm)-and hybrid gyroid TPMS latticed implants with solid necks in corresponding sizes-HI_111, HI_222, and HI_333. To enhance initial stability, a square-threaded design was added into the bottom part of both fully and hybrid lattice implants. The designs also incorporate anti-rotational connections to enhance fixation, and they undergo a clinical viability comparison with contemporary implants. To improve lattice designs, finite element analysis (FEA) was utilized through nTopology (nTOP 4.17.3) to balance stiffness and flexibility. To examine mechanical performance under realistic conditions, a dynamic mastication loading simulation was conducted for 1.5 s across three cycles.

The findings reveal that hybrid implants, particularly HI_222, exhibited improved mechanical characteristics by reducing micromotions at the bone-implant interface, improving osteointegration, and attaining better stress distribution.

By addressing stress shielding and boosting implant performance, this work paves the way for personalized implant designs, developing dental technology, and improving clinical results.

Periodontal diseases, if untreated, can cause gum recession and tooth root exposure, resulting in infection and irreversible damage. Traditional treatments using autologous grafts are painful and often result in postoperative complications. Scaffolds offer a less invasive alternative, promoting cell proliferation and healing without additional surgery, thus enhancing comfort for patients and doctors. This study developed Chitosan (Chit)/Collagen (Col) film surfaces and drug-loaded Polyvinyl Alcohol (PVA)/Amoxicillin (AMX) nanofibers using solvent casting and electrospinning methods, respectively. The surfaces are characterized by scanning electron microscopy (SEM), mechanical testing, Fourier Transform Infrared Spectroscopy (FTIR), and differential scanning calorimetry (DSC). Biocompatibility and antimicrobial properties are assessed using NIH/3T3 fibroblast cells and bacterial cultures. SEM images confirmed the structural integrity of AMX-loaded 13% PVA nanofibers, while FTIR analysis validated the compositional integrity of PVA/AMX nanofibers and Chit/Col film hybrid surfaces. Cell studies showed over 90% viability for Chit/Col film + PVA/AMX nanofiber hybrid bilayer membranes, confirming their biocompatibility. The antimicrobial assessment indicated that the Chit/Col film + PVA/AMX (0.2%) nanofiber hybrid bilayer membrane exhibited superior efficacy against Streptococcus mutans. These findings suggest that this hybrid bilayer membrane can enhance cell growth, promote proliferation, and enable controlled drug release, offering significant promise for regeneration of gingival tissues.

The design and optimization of bone scaffolds are critical for the success of bone tissue engineering (BTE) applications. This review paper provides a comprehensive analysis of computational optimization methods for bone scaffold architecture, focusing on the balance between mechanical stability, biological compatibility, and manufacturability. Finite element method (FEM), computational fluid dynamics (CFD), and various optimization algorithms are discussed for their roles in simulating and refining scaffold designs. The integration of multiobjective optimization and topology optimization has been highlighted for developing scaffolds that meet the multifaceted requirements of BTE. Challenges such as the need for consideration of manufacturing constraints and the incorporation of degradation and bone regeneration models into the optimization process have been identified. The review underscores the potential of advanced computational tools and additive manufacturing techniques in evolving the field of BTE, aiming to improve patient outcomes in bone tissue regeneration. The reliability of current optimization methods is examined, with suggestions for incorporating non-deterministic approaches andin vivovalidations to enhance the practical application of optimized scaffolds. The review concludes with a call for further research into artificial intelligence-based methods to advance scaffold design and optimization.

Bicontinuous interfacially-jammed emulsion gels (bijels) are increasingly used as emulsion templates for the fabrication of functional porous materials including membranes, electrodes, and biomaterials. Control over the domain size and structure is highly desirable in these applications. For bijels stabilized by spherical particles, particle size and volume fraction are the main parameters that determine the emulsion structure. Here, we investigate the use of ellipsoidal magnetic particles and study the effect of external magnetic fields on the formation of bijels. Using hybrid Lattice Boltzmann-molecular dynamics simulations, we analyze the effect of the magnetic field on emulsion dynamics and the structural properties of the resulting bijel. We find that the formation of bijels remains robust in the presence of magnetic fields, and that the domain size and tortuosity become anisotropic when ellipsoidal particles are used. We show that the magnetic fields lead to orientational ordering of the particles which in turn leads to alignment of the interfaces. The orientational order facilitates enhanced packing of particles in the interface which leads to different jamming times in the directions parallel and perpendicular to the field. Our results highlight the potential of magnetic particles for fabrication and processing of emulsion systems with tunable properties.

Elbow stiffness is an uncommon condition that significantly impacting a patient's daily activities. Trauma is the most frequent cause of elbow stiffness. However, capitellum fractures are rare, accounting for approximately 1 % of elbow fractures. They are often misdiagnosed due to nonspecific symptoms and the complex anatomy of the elbow joint.

We report the case of a 54-year-old female who presented with left elbow stiffness eight months after a traumatic incident. On physical examination, her left elbow extension was +10°, and flexion was restricted to 65°, with no limitation in pronation or supination. Imaging studies revealed a malunited capitellum with osteophytes at the posterolateral site of the olecranon. A 3D-printed model of her elbow was created based on a CT scan to aid surgical planning. She underwent capsulectomy and osteotomy and was stabilized with two bioabsorbable P(L/DL)LA pins. Six months postoperatively, the patient's elbow range of motion was fully restored, and no complications were observed.

Elbow stiffness resulting from the malunion of a capitellum fracture typically necessitates surgical intervention to restore functional movement in the elbow.

Capitellum fractures are uncommon and frequently underdiagnosed, leading to complications such as elbow stiffness and reduced functionality. Early detection is crucial, as delayed diagnosis can result in complex management due to malunion. 3D printing from CT scans helps surgeons accurately evaluate malunions and plan precise surgical interventions.

For better bone regeneration, precise control over the architecture of the scaffolds is necessary. Because the shape of the pore may affect the bone regeneration, therefore, additive manufacturing has been used in this study to fabricate magnetic bioactive glass (MBG) scaffolds with three different architectures, namely, grid, gyroid, and Schwarz D surface with 15 × 15 × 15 mm3 dimensions and 70% porosity. These scaffolds have been fabricated using an in-house-developed material-extrusion-based additive manufacturing system. The composition of bioactive glass was selected as 45% SiO2, 20% Na2O, 23% CaO, 6% P2O5, 2.5% B2O3, 1% ZnO, 2% MgO, and 0.5% CaF2 (wt %), and additionally 0.4 wt % of iron carbide nanoparticles were incorporated. Afterward, MBG powder was mixed with a 25% (w/v) Pluronic F-127 solution to prepare a slurry for fabricating scaffolds at 23% relative humidity. The morphological characterization using microcomputed tomography revealed the appropriate pore size distribution and interconnectivity of the scaffolds. The compressive strengths of the fabricated grid, gyroid, and Schwarz D scaffolds were found to be 14.01 ± 1.01, 10.78 ± 1.5, and 12.57 ± 1.2 MPa, respectively. The in vitro study was done by immersing the MBG scaffolds in simulated body fluid for 1, 3, 7, and 14 days. Darcy's law, which describes the flow through porous media, was used to evaluate the permeability of the scaffolds. Furthermore, an anticancer drug (Mitomycin C) was loaded onto these scaffolds, wherein these scaffolds depicted good release behavior. Overall, gyroid-structured scaffolds were found to be the most suitable among the three scaffolds considered in this study for bone tissue engineering and drug-delivery applications.

Titanium-Niobium (TiNb) alloys are commonly employed in a number of implantable devices, yet concerns exist regarding their use in implantology owing to the biomechanical mismatch between the implant and the host tissue. Therefore, to balance the mechanical performance of the load-bearing implant with bone, TiNb alloys with differing porosities were fabricated by powder metallurgy combined with spacer material. Microstructures and phase constituents were characterized with energy dispersive spectroscopy (EDS), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The mechanical properties were tested by uniaxial compression, and the corrosion performance was determined via a potentiodynamic polarization experiment. To evaluate a highly matched potential implant with the host, biocompatibilities such as cell viability and proliferation rate, fibronectin adsorption, plasmid-DNA interaction, and an SEM micrograph showing the cell morphology were examined in detail. The results showed that the alloys displayed open and closed pores with a uniform pore size and distribution, which allowed for cell adherence and other cellular activities. The alloys with low porosity displayed compressive strength between 618 MPa and 1295 MPa, while the alloys with high porosity showed significantly lower strength, ranging from 48 MPa to 331 MPa. The biological evaluation of the alloys demonstrated good cell attachment and proliferation rates.

There is a significant need for models that can capture the mechanical behavior of complex porous lattice architectures produced by 3D printing. The free boundary effect is an experimentally observed behavior of lattice architectures including the gyroid triply periodic minimal surface where the number of unit cell repeats has been shown to influence the mechanical performance of the lattice. The purpose of this study is to use finite element modeling to investigate how architecture porosity, unit cell size, and sample size dictate mechanical behavior. Samples with varying porosity and increasing number of unit cells (relative to sample size) were modeled under an axial compressive load to determine the effective modulus. The finite element model captured the free boundary effect and captured experimental trends in the structure's modulus. The findings of this study show that samples with higher porosity are more susceptible to the impact of the free boundary effect and in some samples, the modulus can be 20% smaller in samples with smaller numbers of unit cell repeats within a given sample boundary. The outcomes from this study provide a deeper understanding of the gyroid structure and the implications of design choices including porosity, unit cell size, and overall sample size.

Intrinsic permeability describes the ability of a porous medium to be penetrated by a fluid. Considering porous scaffolds for tissue engineering (TE) applications, this macroscopic variable can strongly influence the transport of oxygen and nutrients, the cell seeding process, and the transmission of fluid forces to the cells, playing a crucial role in determining scaffold efficacy. Thus, accurately measuring the permeability of porous scaffolds could represent an essential step in their optimization process. In literature, several methods have been proposed to characterize scaffold permeability. Most of the currently adopted approaches to assess permeability limit their applicability to specific scaffold structures, hampering protocols standardization, and ultimately leading to incomparable results among different laboratories. The content of novelty of this study is in the proposal of an adaptable test bench and in defining a specific testing protocol, compliant with the ASTM International F2952-22 guidelines, for reliable and repeatable measurements of the intrinsic permeability of TE porous scaffolds. The developed permeability test bench (PTB) exploits the pump-based method, and it is composed of a modular permeability chamber integrated within a closed-loop hydraulic circuit, which includes a peristaltic pump and pressure sensors, recirculating demineralized water. A specific testing protocol was defined for characterizing the pressure drop associated with the scaffold under test, while minimizing the effects of uncertainty sources. To assess the operational capabilities and performance of the proposed test bench, permeability measurements were conducted on PLA scaffolds with regular (PS) and random (RS) micro-architecture and on commercial bovine bone matrix-derived scaffolds (CS) for bone TE. To validate the proposed approach, the scaffolds were as well characterized using an alternative test bench (ATB) based on acoustic measurements, implementing a blind randomized testing procedure. The consistency of the permeability values measured using both the test benches demonstrated the reliability of the proposed approach. A further validation of the PTB's measurement reliability was provided by the agreement between the measured permeability values of the PS scaffolds and the theory-based predicted permeability value. Once validated the proposed PTB, the performed measurements allowed the investigation of the scaffolds' transport properties. Samples with the same structure (guaranteed by the fused-deposition modeling technique) were characterized by similar permeability values, and CS and RS scaffolds showed permeability values in agreement with the values reported in the literature for bovine trabecular bone. In conclusion, the developed PTB and the proposed testing protocol allow the characterization of the intrinsic permeability of porous scaffolds of different types and dimensions under controlled flow regimes, representing a powerful tool in view of providing a reliable and repeatable framework for characterizing and optimizing scaffolds for TE applications.

Hallux rigidus (HR) is a degenerative arthritis affecting the first metatarsophalangeal joint (MTP), leading to pain and functional impairment, particularly during the propulsive phase of walking. The prevalence of HR is about 2.5 % in individuals over 50, but younger individuals can also be affected, as demonstrated in this case.

We report the case of a 26-year-old patient with a body mass index (BMI) of 20.2, who has been suffering from HR for 5 years. The patient presented with walking difficulties, characterized by a limp and impaired propulsion phase, and pain in the right foot due to HR. A comprehensive gait assessment was conducted using a baropodometric platform and integrated smartphone motion sensors. Following the diagnosis, a non-surgical intervention involving the application of a compressed cotton felt foot orthosis at the MTP plantar area was initiated. This intervention aimed to alleviate pain and improve the functional mobility of the right big toe. Post-treatment assessments showed an increase in the big toe's mobility from 0 degrees to 35 degrees, as measured by a digital goniometer.

The application of a soft support, such as compressed cotton felt, at the plantar area of MTP, demonstrated a potential non-surgical therapeutic approach to improve gait and reduce discomfort in HR patients.

This case study underscores the potential benefits of plantar modification in the management of HR.

Modern orthopaedic implants use lattice structures that act as 3D scaffolds to enhance bone growth into and around implants. Stochastic scaffolds are of particular interest as they mimic the architecture of trabecular bone and can combine isotropic properties and adjustable structure. The existing research mainly concentrates on controlling the mechanical and biological performance of periodic lattices by adjusting pore size and shape. Still, less is known on how we can control the performance of stochastic lattices through their design parameters: nodal connectivity, strut density and strut thickness. To elucidate this, four lattice structures were evaluated with varied strut densities and connectivity, hence different local geometry and mechanical properties: low apparent modulus, high apparent modulus, and two with near-identical modulus. Pre-osteoblast murine cells were seeded on scaffolds and cultured in vitro for 28 days. Cell adhesion, proliferation and differentiation were evaluated. Additionally, the expression levels of key osteogenic biomarkers were used to assess the effect of each design parameter on the quality of newly formed tissue. The main finding was that increasing connectivity increased the rate of osteoblast maturation, tissue formation and mineralisation. In detail, doubling the connectivity, over fixed strut density, increased collagen type-I by 140%, increased osteopontin by 130% and osteocalcin by 110%. This was attributed to the increased number of acute angles formed by the numerous connected struts, which facilitated the organization of cells and accelerated the cell cycle. Overall, increasing connectivity and adjusting strut density is a novel technique to design stochastic structures which combine a broad range of biomimetic properties and rapid ossification.

Accurately printing customizable scaffolds is a challenging task because of the complexity of bone tissue composition, organization, and mechanical behavior. Graphene oxide (GO) and poly-L-lactic acid (PLLA) have drawn attention in the field of bone regeneration. However, as far as we know, the Fischer-Koch model of the GO/PLLA association for three-dimensional (3D) printing was not previously reported. This study characterizes the properties of GO/PLLA-printed scaffolds in order to achieve reproducibility of the trabecula, from virtual planning to the printed piece, as well as its response to a cell viability assay. Fourier-transform infrared and Raman spectroscopy were performed to evaluate the physicochemical properties of the nanocomposites. Cellular adhesion, proliferation, and growth on the nanocomposites were evaluated using scanning electron microscopy. Cell viability tests revealed no significant differences among different trabeculae and cell types, indicating that these nanocomposites were not cytotoxic. The Fischer Koch modeling yielded satisfactory results and can thus be used in studies directed at diverse medical applications, including bone tissue engineering and implants.

The ability of bone to regenerate itself through mechanobiological responses is its dynamic property. Mechanical cues from a neighboring environment produce the structural strain to promote blood flow and bone marrow mobility that in turn aids the bone regeneration process. Occurrences of these phenomena are crucial for the success of metallic scaffolds implanted in the host bone tissue. Thus, permeability and fluid flow-induced wall shear stress (WSS) are two parameters that directly influence cell bioactivities inside a scaffold and are crucial for effective bone tissue regeneration. Given that the scaffolds shall be implanted in the body, permeability assessment was carried out using non-Newtonian fluid. In this work, the triply periodic minimal surface scaffolds with Neovius architectures were fabricated by using selective laser melting technology. The estimation of fluid flow was carried out using computational fluid dynamics (CFD) analysis with a non-Newtonian blood fluid model. Further, the structural strength of various open cell Neovius lattices was evaluated using a static compression test, and in vitro cell culture using Alamar blue assay was evaluated. Results revealed that the values of intrinsic blood flow permeability of the three-dimensional (3D)-printed open cell porous scaffold with Neovius architecture were of the same order of magnitude as those of human bone, ranging from 0.0025 × 10-9 to 0.0152 × 10-9 m2. The structural elastic modulus and compressive strength of NOCL40, NOCL50, and NOCL60 lattices range from 3.27 to 3.71 GPa and 194 to 205 MPa, respectively. All of the values are comparable to the human bone, thus making these lattices a suitable alternative for orthopedic applications.

Background: Revision hip arthroplasty presents a surgical challenge, necessitating meticulous preoperative planning to avert complications like periprosthetic fractures and aseptic loosening. Historically, assessment of the accuracy of three-dimensional (3D) versus two-dimensional (2D) templating has focused exclusively on primary hip arthroplasty. Materials and Methods: In this retrospective study, we examined the accuracy of 3D templating for acetabular revision cups in 30 patients who underwent revision hip arthroplasty. Utilizing computed tomography scans of the patients' pelvis and 3D templates of the implants (Aesculap Plasmafit, B. Braun; Aesculap Plasmafit Revision, B. Braun; Avantage Acetabular System, Zimmerbiomet, EcoFit 2M, Implantcast; Tritanium Revision, Stryker), we performed 3D templating and positioned the acetabular cup implants accordingly. To evaluate accuracy, we compared the planned sizes of the acetabular cups in 2D and 3D with the sizes implanted during surgery. Results: An analysis was performed to examine potential influences on templating accuracy, specifically considering factors such as gender and body mass index (BMI). Significant statistical differences (p < 0.001) in the accuracy of size prediction were observed between 3D and 2D templating. Personalized 3D templating exhibited an accuracy rate of 66.7% for the correct prediction of the size of the acetabular cup, while 2D templating achieved an exact size prediction in only 26.7% of cases. There were no statistically significant differences between the 2D and 3D templating methods regarding gender or BMI. Conclusion: This study demonstrates that 3D templating improves the accuracy of predicting acetabular cup sizes in revision arthroplasty when compared to 2D templating. However, it should be noted that the predicted implant size generated through 3D templating tended to overestimate the implanted implant size by an average of 1.3 sizes.

Unintended rotation of the distal tibia occurs during medial open-wedge high tibial osteotomy (MOWHTO). Computed tomography (CT) is the standard method of measuring lower limb alignment; however, the new low-dose EOS system allows three-dimensional limb modeling with automated measurements of lower limb alignment. This study investigated the differences between the changes in lower limb alignment profiles obtained using the EOS system and CT in patients who underwent MOWHTO. We investigated whether any factors contributed to the degree of deformation. Thirty patients were prospectively enrolled between October 2019 and February 2023. Changes in femoral and tibial torsion, femorotibial rotation, and posterior tibial slope were measured using pre- and post-MOWHTO CT and EOS images. We found no significant difference in pre- and postoperative tibial torsion or posterior tibial slope between CT and EOS. No variables showed a significant correlation with changes in the tibial torsion or posterior tibial slope. This study confirmed the possibility that the EOS system could replace CT in measuring changes in several parameters pre- and postoperatively. Furthermore, we confirmed that the distal tibia tended to be internally rotated after MOWHTO; however, we found no significantly related parameters related to deformation caused by MOWHTO.

Headaches are a common side effect of vaccination against the severe acute respiratory syndrome, coronavirus 2; however, it is usually not necessary to seek emergency medical attention or undergo brain imaging such as non-enhanced brain computed tomography (CT) for routine evaluation of vaccine-related headaches. This study aimed to demonstrate that brain CT is of no clinical benefit to patients presenting to the emergency department (ED) with post-coronavirus disease 2019 (COVID-19) vaccination headaches. This retrospective, single-center observational study used electronic medical record (EMR) data of patients who received the COVID-19 vaccination during the first year of the vaccination program. In total, 914 patients were analyzed, of whom 435 underwent CT (CT group, n = 435; no CT group, n = 475). More female patients visited the ED, and there was no significant sex difference between the CT and no-CT groups. The type of vaccine affected the clinical decision to perform brain CT, but the number of doses did not. The CT rate was relatively high for patients who had received the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and Johnson and Johnson Janssen (Jansen) vaccines (p = 0.004). Focal neurological deficits were present in all cases of abnormalities on non-enhanced brain CT in patients complaining of headaches. Two out of the 435 patients had abnormal brain CT findings (glioblastoma and Rathke's pouch cyst) at 35 and 32 days after vaccination, respectively. Non-enhanced brain CT should be performed cautiously in patients visiting the ED for post-vaccination headaches only.

Binder jetting is a highly productive additive manufacturing (AM) method for porous parts. Due to its cost-effectiveness, it is used for large components and quantities ranging from prototyping to series production. Post-processing steps like sintering or infiltration are common in several applications to achieve high density and strength. This work investigates how 3D-printed sand molds can be infiltrated with epoxy resins without vacuum assistance to produce high-strength molds for thermoforming applications. Specimens 3D-printed from different sand types are infiltrated with resins of different viscosity and analyzed for infiltration velocity and depth. The infiltration velocities corresponded well with the correlation described in Washburn's equation: The resins' viscosities and the saturation level were decisive. Amongst the investigated sand types commonly used in foundries, sand type GS19 was found most suitable for infiltration. However, the sand type proved to be a less relevant influencing factor than the resins' viscosities and quantities applied. Infiltration of topology-optimized 3D-printed sand tools up to a wall thickness of 20 mm for thermoforming applications was found to be feasible.

Diffusion is one of the key nature processes which plays an important role in respiration, digestion, and nutrient transport in cells. In this regard, the present article aims to review various diffusion approaches used to fabricate different functional materials based on hydrogels, unique examples of materials that control diffusion. They have found applications in fields such as drug encapsulation and delivery, nutrient delivery in agriculture, developing materials for regenerative medicine, and creating stimuli-responsive materials in soft robotics and microrobotics. In addition, mechanisms of release and drug diffusion kinetics as key tools for material design are discussed.

The objective of this study was to assess and compare the internal adaptation of various pulp-capping materials, namely TheraCal, Biodentine, and mineral trioxide aggregate (MTA), on the dentin of permanent teeth through the utilization of micro-computed tomography (MCT) and optical coherence tomography (OCT). Thirty permanent molars were divided into three groups using a random process: group A (TheraCal), group B (Biodentine), and group C (MTA, which served as the control group). On the buccal surface of each tooth, a class V cavity of a standardized cylindrical shape was prepared. Subsequently, the respective pulp-capping material was applied to the cavity based on the assigned group, followed by restoration with composite resin. Based on the MCT results, it was observed that group A had a considerably larger gap volume in comparison to groups B and C (p < 0.001). There was no significant difference in gap volume between groups B and C. Regarding the OCT findings, group A displayed a substantially higher level of light reflection than groups B and C (p < 0.001). Group C exhibited a significantly lower level of light reflection in comparison to group B (p < 0.001). Biodentine and MTA revealed similar outcomes in terms of how well they adhered to the dentinal surface in permanent teeth. Both materials exhibited superior performance in comparison to TheraCal. The utilization of OCT in clinical practice could be advantageous as it enables dentists to monitor and evaluate restorations during post-treatment follow-up. It is imperative to intensify efforts aimed at making OCT equipment more accessible and applicable, overcoming its current limitations, and allowing for its widespread utilization in clinical practice.

In the present study, through a case series, we highlighted the role of magnetic resonance (MR) in the identification and diagnosis of peripheral neuropathies. MR neurography allows the evaluation of the course of nerves through 2D and 3D STIR sequences with an isotropic voxel, whereas the relationship between nerves, vessels, osteo-ligamentous and muscular structures can be appraised with T1 sequences. Currently, DTI and tractography are mainly used for experimental purposes. MR neurography can be useful in detecting subtle nerve alterations, even before the onset of symptoms. However, despite being sensitive, MR neurography is not specific in detecting nerve injury and requires careful interpretation. For this reason, MR information should always be supported by instrumental clinical tests.

The biological enhancement of tissue regeneration and healing is an appealing perspective in orthopedics. We aimed to conduct a systematic review to describe the global distribution of studies investigating the use of adipose tissue derivates in orthopedics and to provide information on their quality and on the products available. The quality of the included studies was assessed using the modified Coleman Methodology Score (mCMS) and the Cochrane risk-of-bias tool for randomized trials. Eighty-two studies were included, with a total of 3594 patients treated. In total, 70% of the studies investigated the treatment of knee disorders, predominantly osteoarthritis; 26% of all studies dealt with expanded adipose-derived stem/stromal cells (ADSCs), 72% of which had stromal vascular fraction (SVF); 70% described the injection of adipose tissue derivates into the affected site; and 24% described arthroscopies with the addition of adipose tissue derivates. The mean mCMS for all studies was 51.7 ± 21.4 points, with a significantly higher score for the studies dealing with expanded ADSCs compared to those dealing with SVF (p = 0.0027). Our analysis shows high heterogeneity in terms of the types of performed procedures as well as the choice and processing of adipose tissue derivates.

The femoral neck dynamic intersection system (FNS) is mechanically more stable than other internal fixation techniques. Current studies have confirmed that the structural design of FNS has good biomechanical properties in European and American populations. However, whether the suitability of the FNS's 130° main nail angle design for Asian populations has been thoroughly investigated remains unclear.

To compare the biomechanical stability differences among different main nail angles of the FNS in the treatment of femoral neck fractures in Asian populations.

Computed tomography data of the femur of healthy adult male volunteers were imported into Mimics software to create a three-dimensional model of the femur. The model was adapted to the curve using Geomagic software and imported into Solidworks software to construct the Pauwels I femoral neck fracture model and design the FNS internal fixation model using different main nail angles. Afterward, the models were assembled with the FNS fracture model and meshed using the preprocessing Hypermesh software. Subsequently, they were imported into Abaqus software to analyze and evaluate the biomechanical effects of different angles of the FNS main nail on the treatment of femoral neck fractures.

The peak displacement of the proximal femur under different angles of FNS fixation under stress was 7.446 millimeters in the 120° group and 7.416 millimeters in the 125° group; in the 130°, 135°, and 140° FNS fixation groups, the peak displacement was 7.324 millimeters, 8.138 millimeters, and 8.246 millimeters, respectively. In the 120° and 125° FNS fixation groups, the maximum stresses were concentrated at the main nail and the anti-rotation screw, which intersected the fracture line of the femur neck, resulting in peak stresses of 200.7 MPa and 138.8 MPa, respectively. Peak stresses of 208.8 MPa, 219.8 MPa, and 239.3 MPa were observed on the angular locking plate distal to the locking screw in the 130°, 135°, and 140° fixation groups.

FNS has significant stress distribution properties, a minimal proximal femoral displacement, and an optimal stability for treating femoral neck fractures in Asian populations when performed with a 130° main nail angle.

The increasing evidence of oncocytic renal tumors positive in ^99mTc Sestamibi Single Photon Emission Tomography/Computed Tomography (SPECT/CT) examination calls for the development of diagnostic tools to differentiate these tumors from more aggressive forms. This study combined radiomics analysis with the uptake of ^99mTc Sestamibi on SPECT/CT to differentiate benign renal oncocytic neoplasms from renal cell carcinoma. A total of 57 renal tumors were prospectively collected. Histopathological analysis and radiomics data extraction were performed. XGBoost classifiers were trained using the radiomics features alone and combined with the results from the visual evaluation of ^99mTc Sestamibi SPECT/CT examination. The combined SPECT/radiomics model achieved higher accuracy (95%) with an area under the curve (AUC) of 98.3% (95% CI 93.7-100%) than the radiomics-only model (71.67%) with an AUC of 75% (95% CI 49.7-100%) and visual evaluation of ^99mTc Sestamibi SPECT/CT alone (90.8%) with an AUC of 90.8% (95%CI 82.5-99.1%). The positive predictive values of SPECT/radiomics, radiomics-only, and ^99mTc Sestamibi SPECT/CT-only models were 100%, 85.71%, and 85%, respectively, whereas the negative predictive values were 85.71%, 55.56%, and 94.6%, respectively. Feature importance analysis revealed that ^99mTc Sestamibi uptake was the most influential attribute in the combined model. This study highlights the potential of combining radiomics analysis with ^99mTc Sestamibi SPECT/CT to improve the preoperative characterization of benign renal oncocytic neoplasms. The proposed SPECT/radiomics classifier outperformed the visual evaluation of ^99mTc Sestamibii SPECT/CT and the radiomics-only model, demonstrating that the integration of ^99mTc Sestamibi SPECT/CT and radiomics data provides improved diagnostic performance, with minimal false positive and false negative results.

Three-dimensional cell culture systems hold great promise for bridging the gap between in vitro cell-based model systems and small animal models to study tissue biology and disease. Among 3D cell culture systems, stem-cell-derived spheroids have attracted significant interest as a strategy to better mimic in vivo conditions. Cardiac stem cell/progenitor (CSC)-derived spheroids (CSs) provide a relevant platform for cardiac regeneration.

We compared three different cell culture scaffold-free systems, (i) ultra-low attachment plates, (ii) hanging drops (both requiring a 2D/3D switch), and (iii) agarose micro-molds (entirely 3D), for CSC-derived CS formation and their cardiomyocyte commitment in vitro.

The switch from a 2D to a 3D culture microenvironment per se guides cell plasticity and myogenic differentiation within CS and is necessary for robust cardiomyocyte differentiation. On the contrary, 2D monolayer CSC cultures show a significant reduced cardiomyocyte differentiation potential compared to 3D CS culture. Forced aggregation into spheroids using hanging drop improves CS myogenic differentiation when compared to ultra-low attachment plates. Performing CS formation and myogenic differentiation exclusively in 3D culture using agarose micro-molds maximizes the cardiomyocyte yield.

A 3D culture system instructs CS myogenic differentiation, thus representing a valid model that can be used to study adult cardiac regenerative biology.

The recent understanding of the etiology and pathology of dental caries has shifted its treatment from invasive drill and fill conventional strategies to noninvasive and/or minimally invasive approaches. Guided tissue regeneration (GTR) is a well-established therapeutic approach in medicine and periodontal and oral surgery. Recently, the concept of biomimetic regeneration has been further expanded to treat the loss of hard dental tissues. Self-assembling peptides have emerged as a promising biomaterial for biomimetic regeneration due to their ability to construct a protein scaffold in the body of early carious lesions and provide a matrix that promotes remineralization. This review article accompanies the development of self-assembling peptide P11-4 for the treatment of initial carious lesions. In vitro and in vivo studies on the safety, clinical applicability, and efficacy of P11-4 are discussed. Furthermore, different treatment options and potential areas of application are presented.

Polylactic acid (PLA) is considered a mature alternative to synthetic plastics made from petroleum by-products, possessing the advantages of good mechanical strength. However, it also has some disadvantages such as brittleness and low toughness. In order to overcome and improve some of these unfavorable properties, PLA/PBAT composites were prepared by blending PLA with Poly (butylene adipate-co-terephthalate) (PBAT), and adding 4,4'-methylene diphenyl diisocyanate (MDI) and chitosan nanoparticles (ChNPs) as compatibilizers to investigate the effects of different compatibilizers on the properties of the composites. The main observations are as follows: FT-IR indicated that MDI did not add new groups, while the addition of ChNPs added a substantial amount of hydroxyl and methylene groups. The addition of both MDI and ChNPs did not have any effect on the crystalline shape of the composites, but could potentially reduce their crystallinity, increase the melt peak temperature, wet the boundary of the PLA and PBAT phases, decrease the size of the dispersed phases, reduce the number of dispersed phases, and improve interfacial compatibility. The incorporation of MDI increased the tensile strength from 13.02 MPa to 19.24 MPa, whereas the addition of ChNPs substantially enhanced the elongation at the break from 3.84% to 19.24%. Furthermore, the inclusion of MDI conferred enhanced moisture resistance, whereas the addition of ChNPs seemed to weaken the resistance to moisture.

Bortezomib (BTZ), a chemotherapeutic drug used to treat multiple myeloma, induces life-threatening side effects, including severe pulmonary toxicity. However, the mechanisms underlying these effects remain unclear. The objectives of this study were to (1) investigate whether BTZ influences vascular permeability and (2) clarify the effect of BTZ on the expression of molecules associated with cell-cell junctions using human pulmonary microvascular endothelial cells in vitro. Clinically relevant concentrations of BTZ induced limited cytotoxicity and increased the permeability of human pulmonary microvascular endothelial cell monolayers. BTZ decreased the protein expression of claudin-5, occludin, and VE-cadherin but not that of ZO-1 and β-catenin. Additionally, BTZ decreased the mRNA expression of claudin-5, occludin, ZO-1, VE-cadherin, and β-catenin. Our results suggest that BTZ increases the vascular permeability of the pulmonary microvascular endothelium by downregulating cell-cell junction molecules, particularly claudin-5, occludin, and VE-cadherin.

Myocardial remodeling is an inevitable risk factor for cardiac arrhythmias and can potentially be corrected with cell therapy. Although the generation of cardiac cells ex vivo is possible, specific approaches to cell replacement therapy remain unclear. On the one hand, adhesive myocyte cells must be viable and conjugated with the electromechanical syncytium of the recipient tissue, which is unattainable without an external scaffold substrate. On the other hand, the outer scaffold may hinder cell delivery, for example, making intramyocardial injection difficult. To resolve this contradiction, we developed molecular vehicles that combine a wrapped (rather than outer) polymer scaffold that is enveloped by the cell and provides excitability restoration (lost when cells were harvested) before engraftment. It also provides a coating with human fibronectin, which initiates the process of graft adhesion into the recipient tissue and can carry fluorescent markers for the external control of the non-invasive cell position. In this work, we used a type of scaffold that allowed us to use the advantages of a scaffold-free cell suspension for cell delivery. Fragmented nanofibers (0.85 µm ± 0.18 µm in diameter) with fluorescent labels were used, with solitary cells seeded on them. Cell implantation experiments were performed in vivo. The proposed molecular vehicles made it possible to establish rapid (30 min) electromechanical contact between excitable grafts and the recipient heart. Excitable grafts were visualized with optical mapping on a rat heart with Langendorff perfusion at a 0.72 ± 0.32 Hz heart rate. Thus, the pre-restored grafts' excitability (with the help of a wrapped polymer scaffold) allowed rapid electromechanical coupling with the recipient tissue. This information could provide a basis for the reduction of engraftment arrhythmias in the first days after cell therapy.

Silica aerogel is a material composed of SiO₂ that has exceptional physical properties when utilized for tissue engineering applications. Poly-ε-caprolactone (PCL) is a biodegradable polyester that has been widely used for biomedical applications, namely as sutures, drug carriers, and implantable scaffolds. Herein, a hybrid composite of silica aerogel, prepared with two different silica precursors, tetraethoxysilane (TEOS) or methyltrimethoxysilane (MTMS), and PCL was synthesized to fulfil bone regeneration requirements. The developed porous hybrid biocomposite scaffolds were extensively characterized, regarding their physical, morphological, and mechanical features. The results showed that their properties were relevant, leading to composites with different properties. The water absorption capacity and mass loss were evaluated as well as the influence of the different hybrid scaffolds on osteoblasts' viability and morphology. Both hybrid scaffolds showed a hydrophobic character (with water contact angles higher than 90°), low swelling (maximum of 14%), and low mass loss (1-7%). hOB cells exposed to the different silica aerogel-PCL scaffolds remained highly viable, even for long periods of incubation (7 days). Considering the obtained results, the produced hybrid scaffolds may be good candidates for future application in bone tissue engineering.

The use of fertilizer is closely related to crop growth and environmental protection in agricultural production. It is of great significance to develop environmentally friendly and biodegradable bio-based slow-release fertilizers. In this work, porous hemicellulose-based hydrogels were created, which had excellent mechanical properties, water retention properties (the water retention ratio in soil was 93.8% after 5 d), antioxidant properties (76.76%), and UV resistance (92.2%). This improves the efficiency and potential of its application in soil. In addition, electrostatic interaction and coating with sodium alginate produced a stable core-shell structure. The slow release of urea was realized. The cumulative release ratio of urea after 12 h was 27.42% and 11.38%, and the release kinetic constants were 0.0973 and 0.0288, in aqueous solution and soil, respectively. The sustained release results demonstrated that urea diffusion in aqueous solution followed the Korsmeyer-Peppas model, indicating the Fick diffusion mechanism, whereas diffusion in soil adhered to the Higuchi model. The outcomes show that urea release ratio may be successfully slowed down by hemicellulose hydrogels with high water retention ability. This provides a new method for the application of lignocellulosic biomass in agricultural slow-release fertilizer.

Treatment of large segmental bone loss caused by fractures, osteomyelitis, and non-union results in expenses of around USD 300,000 per case. Moreover, the worst-case scenario results in amputation in 10% to 14.5% of cases. Biomaterials, cells, and regulatory elements are employed in bone tissue engineering (BTE) to create biosynthetic bone grafts with effective functionalization that can aid in the restoration of such fractured bones, preventing amputation and alleviating expenses. Chitin (CT) and chitosan (CS) are two of the most prevalent natural biopolymers utilized in the fields of biomaterials and BTE. To offer the structural and biochemical cues for augmenting bone formation, CT and CS can be employed alone or in combination with other biomaterials in the form of nanofibers (NFs). When compared with several fabrication methods available to produce scaffolds, electrospinning is regarded as superior since it enables the development of nanostructured scaffolds utilizing biopolymers. Electrospun nanofibers (ENFs) offer unique characteristics, including morphological resemblance to the extracellular matrix, high surface-area-to-volume ratio, permeability, porosity, and stability. This review elaborates on the recent strategies employed utilizing CT and CS ENFs and their biocomposites in BTE. We also summarize their implementation in supporting and delivering an osteogenic response to treat critical bone defects and their perspectives on rejuvenation. The CT- and CS-based ENF composite biomaterials show promise as potential constructions for bone tissue creation.

The limited regenerative capacity of the human body, in conjunction with a shortage of healthy autologous tissue, has created an urgent need for alternative grafting materials. A potential solution is a tissue-engineered graft, a construct which supports and integrates with host tissue. One of the key challenges in fabricating a tissue-engineered graft is achieving mechanical compatibility with the graft site; a disparity in these properties can shape the behaviour of the surrounding native tissue, contributing to the likelihood of graft failure. The purpose of this review is to examine the means by which researchers have altered the mechanical properties of tissue-engineered constructs via hybrid material usage, multi-layer scaffold designs, and surface modifications. A subset of these studies which has investigated the function of their constructs in vivo is also presented, followed by an examination of various tissue-engineered designs which have been clinically translated.

Opuntia Ficus-indica, or nopal, is traditionally used for its medicinal properties in Mexico. This study aims to decellularize and characterize nopal (Opuntia Ficus-indica) scaffolds, assess their degradation and the proliferation of hDPSC, and determine potential pro-inflammatory effects by assessing the expression of cyclooxygenase 1 and 2 (COX-1 and 2). The scaffolds were decellularized using a 0.5% sodium dodecyl sulfate (SDS) solution and confirmed by color, optical microscopy, and SEM. The degradation rates and mechanical properties of the scaffolds were determined by weight and solution absorbances using trypsin and PBS and tensile strength testing. Human dental pulp stem cells (hDPSCs) primary cells were used for scaffold-cell interaction and proliferation assays, as well as an MTT assay to determine proliferation. Proinflammatory protein expression of COX-I and -II was discovered by Western blot assay, and the cultures were induced into a pro-inflammatory state with interleukin 1-β. The nopal scaffolds exhibited a porous structure with an average pore size of 252 ± 77 μm. The decellularized scaffolds showed a 57% reduction in weight loss during hydrolytic degradation and a 70% reduction during enzymatic degradation. There was no difference in tensile strengths between native and decellularized scaffolds (12.5 ± 1 and 11.8 ± 0.5 MPa). Furthermore, hDPSCs showed a significant increase in cell viability of 95% and 106% at 168 h for native and decellularized scaffolds, respectively. The combination of the scaffold and hDPSCs did not cause an increase in the expression of COX-1 and COX-2 proteins. However, when the combination was exposed to IL-1β, there was an increase in the expression of COX-2. This study demonstrates the potential application of nopal scaffolds in tissue engineering and regenerative medicine or dentistry, owing to their structural characteristics, degradation properties, mechanical properties, ability to induce cell proliferation, and lack of enhancement of pro-inflammatory cytokines.

This study leverages the advantages of two fabrication techniques, namely, melt-extrusion-based 3D printing and porogen leaching, to develop multiphasic scaffolds with controllable properties essential for scaffold-guided dental tissue regeneration. Polycaprolactone-salt composites are 3D-printed and salt microparticles within the scaffold struts are leached out, revealing a network of microporosity. Extensive characterization confirms that multiscale scaffolds are highly tuneable in terms of their mechanical properties, degradation kinetics, and surface morphology. It can be seen that the surface roughness of the polycaprolactone scaffolds (9.41 ± 3.01 µm) increases with porogen leaching and the use of larger porogens lead to higher roughness values, reaching 28.75 ± 7.48 µm. Multiscale scaffolds exhibit improved attachment and proliferation of 3T3 fibroblast cells as well as extracellular matrix production, compared with their single-scale counterparts (an approximate 1.5- to 2-fold increase in cellular viability and metabolic activity), suggesting that these structures could potentially lead to improved tissue regeneration due to their favourable and reproducible surface morphology. Finally, various scaffolds designed as a drug delivery device were explored by loading them with the antibiotic drug cefazolin. These studies show that by using a multiphasic scaffold design, a sustained drug release profile can be achieved. The combined results strongly support the further development of these scaffolds for dental tissue regeneration applications.

Total hip arthroplasty (THA) is most likely one of the most successful surgical procedures in medicine. It is estimated that three in four patients live beyond the first post-operative year, so appropriate surgery is needed to alleviate an otherwise long-standing suboptimal functional level. However, research has shown that during a complete THA procedure, a solid hip implant inserted in the femur can damage the main arterial supply of the cortex and damage the medullary space, leading to cortical bone resorption. Therefore, this study aimed to design a porous hip implant with a focus on providing more space for better osteointegration, improving the medullary revascularisation and blood circulation of patients. Based on a review of the literature, a lightweight implant design was developed by applying topology optimisation and changing the materials of the implant. Gyroid and Voronoi lattice structures and a solid hip implant (as a control) were designed. In total, three designs of hip implants were constructed by using SolidWorks and nTopology software version 2.31. Point loads were applied at the x, y and z-axis to imitate the stance phase condition. The forces represented were x = 320 N, y = -170 N, and z = -2850 N. The materials that were used in this study were titanium alloys. All of the designs were then simulated by using Marc Mentat software version 2020 (MSC Software Corporation, Munich, Germany) via a finite element method. Analysis of the study on topology optimisation demonstrated that the Voronoi lattice structure yielded the lowest von Mises stress and displacement values, at 313.96 MPa and 1.50 mm, respectively, with titanium alloys as the materials. The results also indicate that porous hip implants have the potential to be implemented for hip implant replacement, whereby the mechanical integrity is still preserved. This result will not only help orthopaedic surgeons to justify the design choices, but could also provide new insights for future studies in biomechanics.

Electrospinning has recently been recognized as a potential method for use in biomedical applications such as nanofiber-based drug delivery or tissue engineering scaffolds. The present study aimed to demonstrate the electrospinning preparation and suitability of β-tricalcium phosphate-modified aerogel containing polyvinyl alcohol/chitosan fibrous meshes (BTCP-AE-FMs) for bone regeneration under in vitro and in vivo conditions. The mesh physicochemical properties included a 147 ± 50 nm fibrous structure, in aqueous media the contact angles were 64.1 ± 1.7°, and it released Ca, P, and Si. The viability of dental pulp stem cells on the BTCP-AE-FM was proven by an alamarBlue assay and with a scanning electron microscope. Critical-size calvarial defects in rats were performed as in vivo experiments to investigate the influence of meshes on bone regeneration. PET imaging using ¹⁸F-sodium fluoride standardized uptake values (SUVs) detected 7.40 ± 1.03 using polyvinyl alcohol/chitosan fibrous meshes (FMs) while 10.72 ± 1.11 with BTCP-AE-FMs after 6 months. New bone formations were confirmed by histological analysis. Despite a slight change in the morphology of the mesh because of cross-linking, the BTCP-AE-FM basically retained its fibrous, porous structure and hydrophilic and biocompatible character. Our experiments proved that hybrid nanospun scaffold composite mesh could be a new experimental bone substitute bioactive material in future medical practice.

Retinal degenerative diseases such as age-related macular degeneration (AMD) represent a leading cause of blindness, resulting in permanent damage to retinal cells that are essential for maintaining normal vision. Around 12% of people over the age of 65 have some form of retinal degenerative disease. Whilst antibody-based drugs have revolutionised treatment of neovascular AMD, they are only effective at an early stage and cannot prevent eventual progression or allow recovery of previously lost vision. Hence, there is a clear unmet need to find innovative treatment strategies to develop a long-term cure. The replacement of damaged retinal cells is thought to be the best therapeutic strategy for the treatment of patients with retinal degeneration. Advanced therapy medicinal products (ATMPs) are a group of innovative and complex biological products including cell therapy medicinal products, gene therapy medicinal products, and tissue engineered products. Development of ATMPs for the treatment of retinal degeneration diseases has become a fast-growing field of research because it offers the potential to replace damaged retinal cells for long-term treatment of AMD. While gene therapy has shown encouraging results, its effectiveness for treatment of retinal disease may be hampered by the body's response and problems associated with inflammation in the eye. In this mini-review, we focus on describing ATMP approaches including cell- and gene-based therapies for treatment of AMD along with their applications. We also aim to provide a brief overview of biological substitutes, also known as scaffolds, that can be used for delivery of cells to the target tissue and describe biomechanical properties required for optimal delivery. We describe different fabrication methods for preparing cell-scaffolds and explain how the use of artificial intelligence (AI) can aid with the process. We predict that combining AI with 3D bioprinting for 3D cell-scaffold fabrication could potentially revolutionise retinal tissue engineering and open up new opportunities for developing innovative platforms to deliver therapeutic agents to the target tissues.

Background and Objectives: This study evaluated the effectiveness of Hyalofast cartilage repair surgery with an early, full load-bearing rehabilitation program one day after the operation for reducing the time needed for professional athletes to return to play. Materials and Methods: This prospective study included 49 patients aged between 19 and 38 years who had undergone surgical reconstruction of cartilage using the microfracture technique combined with a Hyalofast scaffold. All patients were active professional athletes. Early rehabilitation was implemented from the first postoperative day, fully loading the operated limb. A clinical evaluation was based on the KOOS and SF-36 questionnaires used during subsequent follow-up visits. All patients underwent magnetic resonance imaging (MRI) to evaluate the effect of the surgery after one year. Results: The clinical results demonstrated a statistically significant improvement in the number of complaints about pain and in the quality of life of the patients, measured in all of the applied scales, with comparisons made between six months or one year post-surgery and pre-surgery. Importantly for athletes, the parameter related to sports and recreation improved from 14 ± 11.1 to 95 ± 7.7 6 months after surgery and to 99.8 ± 1.8 one year after surgery. The overall quality of life score improved from 30 ± 18 to 88 ± 8.8 one year after surgery. Conclusions: These results show that this approach significantly shortened the time needed for the athletes to return to sports at the same level as before the surgery (athletes returned to sports in approximately 2.5-3 months). The mean follow-up time was 19.75 months. This technique can be considered a viable option for the treatment of cartilage injuries in professional athletes, allowing them to return to play more quickly in a safe and healthy way.

Recently, substantial attention has been paid toward adipose-derived mesenchymal stem cells (AdMSCs) as a potential therapy in tissue engineering and regenerative medicine applications. Rat AdMSCs (r-AdMSCs) are frequently utilized. However, the influence of the adipose depot site on the multilineage differentiation potential of the r-AdMSCs is still ambiguous. Hence, the main objective of this study was to explore the influence of the adipose tissue harvesting location on the ability of r-AdMSCs to express the stem-cell-related markers and pluripotency genes, as well as their differentiation capacity, for the first time. Herein, we have isolated r-AdMSCs from the inguinal, epididymal, peri-renal, and back subcutaneous fats. Cells were compared in terms of their phenotype, immunophenotype, and expression of pluripotency genes using RT-PCR. Additionally, we investigated their potential for multilineage (adipogenic, osteogenic, and chondrogenic) induction using special stains confirmed by the expression of the related genes using RT-qPCR. All cells could positively express stem cell marker CD 90 and CD 105 with no significant in-between differences. However, they did not express the hematopoietic markers as CD 34 and CD 45. All cells could be induced successfully. However, epididymal and inguinal cells presented the highest capacity for adipogenic and osteogenic differentiation (21.36-fold and 11.63-fold for OPN, 29.69-fold and 26.68-fold for BMP2, and 37.67-fold and 22.35-fold for BSP, respectively, in epididymal and inguinal cells (p < 0.0001)). On the contrary, the subcutaneous cells exhibited a superior potential for chondrogenesis over the other sites (8.9-fold for CHM1 and 5.93-fold for ACAN, (p < 0.0001)). In conclusion, the adipose tissue harvesting site could influence the differentiation capacity of the isolated AdMSCs. To enhance the results of their employment in various regenerative cell-based therapies, it is thus vital to take the collection site selection into consideration.

The most common decellularization method involves lipid removal using surfactant sodium dodecyl sulfate (SDS) and DNA fragmentation using DNase, and is associated with residual SDS. We previously proposed a decellularization method for the porcine aorta and ostrich carotid artery using liquefied dimethyl ether (DME), which is free from the concerns associated with SDS residues, instead of SDS. In this study, the DME + DNase method was tested on crushed porcine auricular cartilage tissues. Unlike with the porcine aorta and the ostrich carotid artery, it is important to degas the porcine auricular cartilage using an aspirator before DNA fragmentation. Although approximately 90% of the lipids were removed using this method, approximately 2/3 of the water was removed, resulting in a temporary Schiff base reaction. The amount of residual DNA in the tissue was approximately 27 ng/mg dry weight, which is lower than the regulatory value of 50 ng/mg dry weight. Hematoxylin and eosin staining confirmed that cell nuclei were removed from the tissue. Residual DNA fragment length assessment by electrophoresis confirmed that the residual DNA was fragmented to less than 100 bp, which was lower than the regulatory limit of 200 bp. By contrast, in the uncrushed sample, only the surface was decellularized. Thus, although limited to a sample size of approximately 1 mm, liquefied DME can be used to decellularize porcine auricular cartilage. Thus, liquefied DME, with its low persistence and high lipid removal capacity, is an effective alternative to SDS.

Large oral bone defects require grafting of bone blocks rather than granules to give physically robust, biocompatible and osteoconductive regeneration. Bovine bone is widely accepted as a source of clinically appropriate xenograft material. However, the manufacturing process often results in both reduced mechanical strength and biological compatibility. The aim of this study was to assess bovine bone blocks at different sintering temperatures and measure the effects on mechanical properties and biocompatibility. Bone blocks were divided into four groups; Group 1: Control (Untreated); Group 2: Initial boil for 6 h; Group 3: Boil 6 h followed by sintering at 550 °C for 6 h; Group 4: Boil 6 h followed by sintering at 1100 °C for 6 h. Samples were assessed for their purity, crystallinity, mechanical strength, surface morphology, chemical composition, biocompatibility and clinical handling properties. Statistical analysis was performed using one-way ANOVA and post-hoc Tukey's tests for normally distributed and Friedman test for abnormally distributed quantitative data from compression tests and PrestoBlue™ metabolic activity tests. The threshold for statistical significance was set at p < 0.05. The results showed that higher temperature sintering (Group 4) removed all organic material (0.02% organic components and 0.02% residual organic components remained) and increased crystallinity (95.33%) compared to Groups 1-3. All test groups (Group 2-4) showed decreased mechanical strength (MPa: 4.21 ± 1.97, 3.07 ± 1.21, 5.14 ± 1.86, respectively) compared with raw bone (Group 1) (MPa: 23.22 ± 5.24, p <0.05), with micro-cracks seen under SEM in Groups 3 and 4. Group 4 had the highest biocompatibility (p < 0.05) with osteoblasts as compared to Group 3 at all time points in vitro. Clinical handling tests indicated that Group 4 samples could better withstand drilling and screw placement but still demonstrated brittleness compared to Group 1. Hence, bovine bone blocks sintered at 1100 °C for 6 h resulted in highly pure bone with acceptable mechanical strength and clinical handling, suggesting it is a viable option as a block grafting material.

The extracellular microenvironment regulates many of the mechanical and biochemical cues that direct musculoskeletal development and are involved in musculoskeletal disease. The extracellular matrix (ECM) is a main component of this microenvironment. Tissue engineered approaches towards regenerating muscle, cartilage, tendon, and bone target the ECM because it supplies critical signals for regenerating musculoskeletal tissues. Engineered ECM-material scaffolds that mimic key mechanical and biochemical components of the ECM are of particular interest in musculoskeletal tissue engineering. Such materials are biocompatible, can be fabricated to have desirable mechanical and biochemical properties, and can be further chemically or genetically modified to support cell differentiation or halt degenerative disease progression. In this review, we survey how engineered approaches using natural and ECM-derived materials and scaffold systems can harness the unique characteristics of the ECM to support musculoskeletal tissue regeneration, with a focus on skeletal muscle, cartilage, tendon, and bone. We summarize the strengths of current approaches and look towards a future of materials and culture systems with engineered and highly tailored cell-ECM-material interactions to drive musculoskeletal tissue restoration. The works highlighted in this review strongly support the continued exploration of ECM and other engineered materials as tools to control cell fate and make large-scale musculoskeletal regeneration a reality.