Search Results (35)

Additive manufacturing (AM) has emerged as a cutting-edge technology for fabricating biomimetic scaffolds with controllable architectures and compositional diversity, showing great promise in the fields of bone tissue engineering (BTE) and regenerative medicine. However, due to limitations in printing resolution and single-process capabilities, AM alone struggles to replicate the complex multiscale hierarchical structures inherent in native bone. Traditional fabrication techniques provide valuable complementary strategies to address these limitations. This review systematically summarizes recent advances in the construction of heterogeneous scaffolds from a multiscale design perspective, encompassing macro-, meso-, and microscale approaches. Emphasis is placed on the integration of major AM techniques—such as extrusion-based and light-based printing—with conventional methods including freeze-drying, gas foaming, and electrospinning. Particular attention is given to emerging in situ fabrication strategies, such as in situ foaming and mineralization, which enable spatially resolved and functionally graded architectures. Furthermore, this review explores pathways for constructing multiscale-integrated scaffolds and examines the current challenges and opportunities in clinical translation. Collectively, this work provides a comprehensive framework to guide the development of next-generation bone tissue scaffolds with enhanced biological performance and translational potential. Full article

Electrospinning is a technique that enables the production of nano- and microfibrillar patterns that mimic the native extracellular matrix. However, these nanofibrous structures often lack mechanical properties suitable for reproducing the behavior of structurally complex tissues. Therefore, achieving more accurate and precise geometric structures be-comes a key challenge. In this context, additive manufacturing techniques such as 3D printing may allow for the development of tailored structures with highly controlled ar-chitecture and improved mechanical strength. However, in contrast with electrospinning, these techniques are commonly considered “low-resolution” techniques, unable to ma-nipulate structural details at the submicrometric scale. Hence, this review aims to intro-duce and discuss recent technological approaches based on combining these technologies for scaffold development in tissue engineering, detailing some distinct integration strate-gies correlating the outcomes to the benefits and drawbacks. Finally, a comprehensive analysis of the current state of the art in the registered intellectual property related to these integrated approaches will be proposed, assessing their distribution by geographic region and analyzing the main trends over time and future fallouts. Full article

Fused deposition modelling (FDM) is an additive manufacturing technique widely used for rapid prototyping. This method facilitates the creation of parts with intricate geometries, making it suitable for advanced applications in fields such as tissue engineering, aerospace, and electronics. Despite its advantages, FDM often results in the formation of voids between the deposited filaments, which can compromise mechanical properties. However, in some cases, such as the design of scaffolds for bone regeneration, increased porosity can be advantageous as it allows for better permeability. On the other hand, the introduction of nano-additives into the FDM material enhances design flexibility and can significantly improve the mechanical properties. Therefore, modelling FDM-produced components involves complexities at two different scales: nanoscales and microscales. Material deformation is primarily influenced by atomic-scale phenomena, especially with nanoscopic constituents, whereas the distribution of nano-reinforcements and FDM-induced heterogeneities lies at the microscale. This work presents multiscale modelling that bridges the nano and microscales to predict the mechanical properties of FDM-manufactured components. At the nanoscale, molecular dynamic simulations unravel the atomistic intricacies that dictate the behaviour of the base material containing nanoscopic reinforcements. Simulations are conducted on polylactic acid (PLA) and PLA reinforced with silver nanoparticles, with the properties derived from MD simulations transferred to the microscale model. At the microscale, non-classical micropolar theory is utilised, which can account for materials’ heterogeneity through internal scale parameters while avoiding direct discretization. The developed mechanical model offers a comprehensive framework for designing 3D-printed PLA nanocomposites with tailored mechanical properties. Full article

Additive and lithographic manufacturing technologies using photopolymerisation provide a powerful tool for fabricating multiscale structures, which is especially interesting for biomimetic scaffolds and biointerfaces. However, most resins are tailored to one particular fabrication technology, showing drawbacks for versatile use. Hence, we used a resin based on thiol-ene chemistry, leveraging its numerous advantages such as low oxygen inhibition, minimal shrinkage and high monomer conversion. The resin is tailored to applications in additive and lithographic technologies for future biofabrication where fast curing kinetics in the presence of oxygen are required, namely 3D inkjet printing, digital light processing and nanoimprint lithography. These technologies enable us to fabricate scaffolds over a span of six orders of magnitude with a maximum of 10 mm and a minimum of 150 nm in height, including bioinspired porous structures with controlled architecture, hole-patterned plates and micro/submicro patterned surfaces. Such versatile properties, combined with noncytotoxicity, degradability and the commercial availability of all the components render the resin as a prototyping material for tissue engineers. Full article

Bacteriotherapy is emerging as a strategic and effective approach to treat infections by providing putatively harmless bacteria (i.e., probiotics) as antagonists to pathogens. Proper delivery of probiotics or their metabolites (i.e., post-biotics) can facilitate their availing of biomaterial encapsulation via innovative manufacturing technologies. This review paper aims to provide the most recent biomaterial-assisted strategies proposed to treat infections or dysbiosis using bacteriotherapy. We revised the encapsulation processes across multiscale biomaterial approaches, which could be ideal for targeting different tissues and suit diverse therapeutic opportunities. Hydrogels, and specifically polysaccharides, are the focus of this review, as they have been reported to better sustain the vitality of the live cells incorporated. Specifically, the approaches used for fabricating hydrogel-based devices with increasing dimensionality (D)—namely, 0D (i.e., particles), 1D (i.e., fibers), 2D (i.e., fiber meshes), and 3D (i.e., scaffolds)—endowed with probiotics, were detailed by describing their advantages and challenges, along with a future overlook in the field. Electrospinning, electrospray, and 3D bioprinting were investigated as new biofabrication methods for probiotic encapsulation within multidimensional matrices. Finally, examples of biomaterial-based systems for cell and possibly post-biotic release were reported. Full article

Although regenerative medicine necessitates advanced three-dimensional (3D) scaffolds for organ and tissue applications, creating intricate structures across scales, from nano- to meso-like biological tissues, remains a challenge. Electrospinning of nanofibers offers promise due to its capacity to craft not only the dimensions and surfaces of individual fibers but also intricate attributes, such as anisotropy and porosity, across various materials. In this study, we used a 3D printer to design a mold with polylactic acid for gel modeling. This gel template, which was mounted on a metal wire, facilitated microfiber electrospinning. After spinning, these structures were treated with EDTA to remove the template and were then cleansed and dried, resulting in 3D microfibrous (3DMF) structures, with average fiber diameters of approximately 1 µm on the outer and inner surfaces. Notably, these structures matched their intended design dimensions without distortion or shrinkage, demonstrating the adaptability of this method for various template sizes. The cylindrical structures showed high elasticity and stretchability with an elastic modulus of 6.23 MPa. Furthermore, our method successfully mimicked complex biological tissue structures, such as the inner architecture of the voice box and the hollow partitioned structure of the heart’s tricuspid valve. Achieving specific intricate shapes required multiple spinning sessions and subsequent assemblies. In essence, our approach holds potential for crafting artificial organs and forming the foundational materials for cell culture scaffolds, addressing the challenges of crafting intricate multiscale structures. Full article

Incorporation of silicate ions in calcium phosphate ceramics (CPC) and modification of their multiscale architecture are two strategies for improving the vascularization of scaffolds for bone regenerative medicine. The response of endothelial cells, actors for vascularization, to the chemical and physical cues of biomaterial surfaces is little documented, although essential. We aimed to characterize in vitro the response of an endothelial cell line, C166, cultivated on the surface CPCs varying either in terms of their chemistry (pure versus silicon-doped HA) or their microstructure (dense versus microporous). Adhesion, metabolic activity, and proliferation were significantly altered on microporous ceramics, but the secretion of the pro-angiogenic VEGF-A increased from 262 to 386 pg/mL on porous compared to dense silicon-doped HA ceramics after 168 h. A tubulogenesis assay was set up directly on the ceramics. Two configurations were designed for discriminating the influence of the chemistry from that of the surface physical properties. The formation of tubule-like structures was qualitatively more frequent on dense ceramics. Microporous ceramics induced calcium depletion in the culture medium (from 2 down to 0.5 mmol/L), which is deleterious for C166. Importantly, this effect might be associated with the in vitro static cell culture. No influence of silicon doping of HA on C166 behavior was detected. Full article

Chromatin regulatory processes physically take place in the environment of the cell nucleus, which is filled with the chromosomes and a plethora of smaller biomolecules. The nucleus contains macromolecular assemblies of different sizes, from nanometer-sized protein complexes to micrometer-sized biomolecular condensates, chromosome territories, and nuclear bodies. This multiscale organization impacts the transport processes within the nuclear interior, the global mechanical properties of the nucleus, and the way the nucleus senses and reacts to mechanical stimuli. Here, we discuss recent work on these aspects, including microrheology and micromanipulation experiments assessing the material properties of the nucleus and its subcomponents. We summarize how the properties of multiscale media depend on the time and length scales probed in the experiment, and we reconcile seemingly contradictory observations made on different scales. We also revisit the concept of liquid-like and solid-like material properties for complex media such as the nucleus. We propose that the nucleus can be considered a multiscale viscoelastic medium composed of three major components with distinct properties: the lamina, the chromatin network, and the nucleoplasmic fluid. This multicomponent organization enables the nucleus to serve its different functions as a reaction medium on the nanoscale and as a mechanosensor and structural scaffold on the microscale. Full article

Type I collagen physiological scaffold for tissue regeneration is considered one of the widely used biomaterials for tissue engineering and medical applications. It is hierarchically organized: five laterally staggered molecules are packed within fibrils, arranged into fascicles and bundles. The structural organization is correlated to the direction and intensity of the forces which can be loaded onto the tissue. For a tissue-specific regeneration, the required macro- and microstructure of a suitable biomaterial has been largely investigated. Conversely, the function of multiscale structural integrity has been much less explored but is crucial for scaffold design and application. In this work, collagen was extracted from different animal sources with protocols that alter its structure. Collagen of tendon shreds excised from cattle, horse, sheep and pig was structurally investigated by wide- and small-angle X-ray scattering techniques, at both molecular and supramolecular scales, and thermo-mechanically with thermal and load-bearing tests. Tendons were selected because of their resistance to chemical degradation and mechanical stresses. The multiscale structural integrity of tendons’ collagen was studied in relation to the animal source, anatomic location and source for collagen extraction. Full article

Cellular materials have a wide range of applications, including structural optimization and biomedical applications. Due to their porous topology, which promotes cell adhesion and proliferation, cellular materials are particularly suited for tissue engineering and the development of new structural solutions for biomechanical applications. Furthermore, cellular materials can be effective in adjusting mechanical properties, which is especially important in the design of implants where low stiffness and high strength are required to avoid stress shielding and promote bone growth. The mechanical response of such scaffolds can be improved further by employing functional gradients of the scaffold’s porosity and other approaches, including traditional structural optimization frameworks; modified algorithms; bio-inspired phenomena; and artificial intelligence via machine learning (or deep learning). Multiscale tools are also useful in the topological design of said materials. This paper provides a state-of-the-art review of the aforementioned techniques, aiming to identify current and future trends in orthopedic biomechanics research, specifically implant and scaffold design. Full article

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. Full article

Clinically, large diameter artery defects (diameter larger than 6 mm) can be substituted by unbiodegradable polymers, such as polytetrafluoroethylene. There are many problems in the construction of small diameter blood vessels (diameter between 1 and 3 mm) and microvessels (diameter less than 1 mm), especially in the establishment of complex vascular models with multi-scale branched networks. Throughout history, the vascularization strategies have been divided into three major groups, including self-generated capillaries from implantation, pre-constructed vascular channels, and three-dimensional (3D) printed cell-laden hydrogels. The first group is based on the spontaneous angiogenesis behaviour of cells in the host tissues, which also lays the foundation of capillary angiogenesis in tissue engineering scaffolds. The second group is to vascularize the polymeric vessels (or scaffolds) with endothelial cells. It is hoped that the pre-constructed vessels can be connected with the vascular networks of host tissues with rapid blood perfusion. With the development of bioprinting technologies, various fabrication methods have been achieved to build hierarchical vascular networks with high-precision 3D control. In this review, the latest advances in 3D bioprinting of vascularized tissues/organs are discussed, including new printing techniques and researches on bioinks for promoting angiogenesis, especially coaxial printing, freeform reversible embedded in suspended hydrogel printing, and acoustic assisted printing technologies, and freeform reversible embedded in suspended hydrogel (flash) technology. Full article

Complex scaffolds composed of micro- and nano-structures are a key target in tissue engineering and the combination of sequential 3D printing and electrospinning enables the fabrication of these multi-scale structures. In this work, dual 3D printed and electrospun polycaprolactone (PCL) scaffolds with multiple mesh layers were successfully prepared. The scaffold macro- and micro-porosity were assessed by optical and scanning electron microscopy, showing that electrospun fibers formed aligned meshes within the pores of the scaffold. Consequently, the hydrophilicity of the scaffold increased with time, enhancing cell adhesion and growth. Additionally, compression tests in back and forth cycles demonstrated a good shape recovery behavior of the scaffolds. Biological results indicated that hybrid PCL scaffolds are biocompatible and enable a correct cell culture over time. Moreover, MC3T3-E1 preosteoblast culture on the scaffolds promoted the mineralization, increased the alkaline phosphatase (ALP) activity and upregulated the expression of early and late osteogenic markers, namely ALP and osteopontin (OPN), respectively. These results demonstrate that the sequential combination of 3D printing and electrospinning provides a facile method of incorporating fibers within a 3D printed scaffold, becoming a promising approach towards multi-scale hierarchical scaffolds capable of guiding the osteogenic differentiation. Full article

Porous organic polymers are versatile platforms, easily adaptable to a wide range of applications, from air filtering to energy devices. Their fabrication via vat photopolymerization enables them to control the geometry on a multiscale level, obtaining hierarchical porosity with enhanced surface-to-volume ratio. In this work, a photocurable ink based on 1,6 Hexanediol diacrylate and containing a high internal phase emulsion (HIPE) is presented, employing PLURONIC F-127 as a surfactant to generate stable micelles. Different parameters were studied to assess the effects on the morphology of the pores, the printability and the mechanical properties. The tests performed demonstrates that only water-in-oil emulsions were suitable for 3D printing. Afterwards, 3D complex porous objects were printed with a Digital Light Processing (DLP) system. Structures with large, interconnected, homogeneous porosity were fabricated with high printing precision (300 µm) and shape fidelity, due to the addition of a Radical Scavenger and a UV Absorber that improved the 3D printing process. The formulations were then used to build scaffolds with complex architecture to test its application as a filter for CO₂ absorption and trapping from environmental air. This was obtained by surface decoration with NaOH nanoparticles. Depending on the surface coverage, tested specimens demonstrated long-lasting absorption efficiency. Full article

Bone is a complex biologic tissue, which is extremely relevant for various physiological functions, in addition to movement, organ protection, and weight bearing. The repair of critical size bone defects is a still unmet clinical need, and over the past decades, material scientists have been expending efforts to find effective technological solutions, based on the use of scaffolds. In this context, biomimetics which is intended as the ability of a scaffold to reproduce compositional and structural features of the host tissues, is increasingly considered as a guide for this purpose. However, the achievement of implants that mimic the very complex bone composition, multi-scale structure, and mechanics is still an open challenge. Indeed, despite the fact that calcium phosphates are widely recognized as elective biomaterials to fabricate regenerative bone scaffolds, their processing into 3D devices with suitable cell-instructing features is still prevented by insurmountable drawbacks. With respect to biomaterials science, new approaches maybe conceived to gain ground and promise for a substantial leap forward in this field. The present review provides an overview of physicochemical and structural features of bone tissue that are responsible for its biologic behavior. Moreover, relevant and recent technological approaches, also inspired by natural processes and structures, are described, which can be considered as a leverage for future development of next generation bioactive medical devices. Full article