3D-printed Scaffolds Research Articles

3D Printing and Surface Engineering of Ti6Al4V Scaffolds for Enhanced Osseointegration in an In Vitro Study.

Ti6Al4V superalloy is recognized as a good candidate for bone implants owing to its biocompatibility, corrosion resistance, and high strength-to-weight ratio. While dense metal implants are associated with stress shielding issues due to the difference in densities, stiffness, and modulus of elasticity compared to bone tissues, the surface of the implant/scaffold should mimic the properties of the bone of interest to assure a good integration with a strong interface. In this study, we investigated the additive manufacturing of porous Ti6Al4V scaffolds and coating modification for enhanced osteoconduction using osteoblast cells. The results showed the successful fabrication of porous Ti6Al4V scaffolds with adequate strength. Additionally, the surface treatment with NaOH and Dopamine Hydrochloride (DOPA) promoted the formation of Dopamine Hydrochloride (DOPA) coating with an optimized coating process, providing an environment that supports higher cell viability and growth compared to the uncoated Ti6Al4V scaffolds, as demonstrated by the higher proliferation ratios observed from day 1 to day 29. These findings bring valuable insights into the surface modification of 3D-printed scaffolds for improved osteoconduction through the coating process in solutions.

3D-printed Mg-incorporated PCL-based scaffolds improves rotator cuff tendon-bone healing through regulating macrophage polarization.

Introduction: Rotator cuff tear (RCT) is a common shoulder injury impacting mobility and quality of life, while traditional surgeries often result in poor healing. Tissue engineering offers a promising solution, with poly (ε-caprolactone) (PCL) being favored due to its slow degradation, biocompatibility, and non-toxicity. However, PCL lacks sufficient compression resistance. Incorporating Mg, which promotes bone growth and has antibacterial effects, could enhance RCT repair. Methods: The Mg-incorporated PCL-based scaffolds were fabricated using a 3D printing technique. The scaffolds were incorporated with different percentages of Mg (0%, 5%, 10%, 15%, and 20%). The osteogenic activities and anti-inflammatory properties of the scaffolds were evaluated in vitro using human osteoblasts and macrophages. The tissue ingrowth and biocompatibility of the scaffolds were assessed in vivo using a rat model of RCT repair. The ability of the scaffolds to enhance macrophage polarization towards the M2 subtype and inhibit inflammation signaling activation was also investigated. Results: It was found that when incorporated with 10% Mg, PCL-based scaffolds exhibited the optimal bone repairing ability in vitro and in vivo. The in vitro experiments indicated that the successfully constructed 10Mg/PCL scaffolds enhance osteogenic activities and anti-inflammatory properties. Besides, the in vivo studies demonstrated that 10Mg/PCL scaffolds promoted tissue ingrowth and enhanced biocompatibility compared to the control PCL scaffolds. Furthermore, the 10Mg/PCL scaffolds enhanced the macrophages' ability to polarize towards the M2 subtype and inhibited inflammation signaling activation. Discussion: These findings suggest that 3D-printed Mg-incorporated PCL scaffolds have the potential to improve RCT by enhancing osteogenesis, reducing inflammation, and promoting macrophage polarization. The incorporation of 10% Mg into PCL-based scaffolds provided the optimal combination of properties for RCT repair augmentation. This study highlights the potential of tissue engineering approaches in improving the outcomes of RCT repair and provides a foundation for future clinical applications.

Ti3C2Tx MXene-Decorated 3D-Printed Ceramic Scaffolds for Enhancing Osteogenesis by Spatiotemporally Orchestrating Inflammatory and Bone Repair Responses.

Inflammatory responses play a central role in coordinating biomaterial-mediated tissue regeneration. However, precise modulation of dynamic variations in microenvironmental inflammation post-implantation remains challenging. In this study, the traditional β-tricalcium phosphate-based scaffold is remodeled via ultrathin MXene-Ti3C2 decoration and Zn2+/Sr2+ ion-substitution, endowing the scaffold with excellent reactive oxygen species-scavenging ability, near-infrared responsivity, and enhanced mechanical properties. The induction of mild hyperthermia around the implant via periodic near-infrared irradiation facilitates spatiotemporal regulation of inflammatory cytokines secreted by a spectrum of macrophage phenotypes. The process initially amplifies the pro-inflammatory response, then accelerates M1-to-M2 macrophage polarization transition, yielding a satisfactory pattern of osteo-immunomodulation during the natural bone healing process. Later, sustained release of Zn2+/Sr2+ ions with gradual degradation of the 3D scaffold maintains the favorable reparative M2-dominated immunological microenvironment that supports new bone mineralization. Precise temporal immunoregulation of the bone healing process by the intelligent 3D scaffold enhances bone regeneration in a rat cranial defect model. This strategy paves the way for the application of β-tricalcium phosphate-based materials to guide the dynamic inflammatory and bone tissue responses toward a favorable outcome, making clinical treatment more predictable and durable. The findings also demonstrate that near-infrared irradiation-derived mild hyperthermia is a promising method of immunomodulation.

Biological and Mechanical Evaluation of Integrated Nano-Hydroxyapatite in 3D-Printed Polylactic Acid Scaffold

Biological and Mechanical Evaluation of Integrated Nano-Hydroxyapatite in 3D-Printed Polylactic Acid Scaffold

3D-printed bone regeneration scaffolds modulate bone metabolic homeostasis through vascularization for osteoporotic bone defects

The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.

3D-Bioprinted Gelatin Methacryloyl-Strontium-Doped Hydroxyapatite Composite Hydrogels Scaffolds for Bone Tissue Regeneration.

New gelatin methacryloyl (GelMA)-strontium-doped nanosize hydroxyapatite (SrHA) composite hydrogel scaffolds were developed using UV photo-crosslinking and 3D printing for bone tissue regeneration, with the controlled delivery capacity of strontium (Sr). While Sr is an effective anti-osteoporotic agent with both anti-resorptive and anabolic properties, it has several important side effects when systemic administration is applied. Multi-layer composite scaffolds for bone tissue regeneration were developed based on the digital light processing (DLP) 3D printing technique through the photopolymerization of GelMA. The chemical, morphological, and biocompatibility properties of these scaffolds were investigated. The composite gels were shown to be suitable for 3D printing. In vitro cell culture showed that osteoblasts can adhere and proliferate on the surface of the hydrogel, indicating that the GelMA-SrHA hydrogel has good cell viability and biocompatibility. The GelMA-SrHA composites are promising 3D-printed scaffolds for bone repair.

Spatiotemporal delivery of BMP-2 and FGF-18 in 3D-bioprinted tri-phasic osteochondral scaffolds enhanced compartmentalized osteogenic and chondrogenic differentiation of mesenchymal stem cells isolated from rats with varied organizational morphologies

Replicating the heterogeneous structure and promoting compartmentalized osteogenesis/chondrogenesis are critical considerations in designing scaffolds for osteochondral tissue regeneration. However, desirable osteochondral regeneration cannot be achieved mainly due to the absence of effective delivery strategies for growth factors (GFs) and the insufficiency of desirable organizational morphologies for seed cells. Herein, we developed a tri-phasic osteochondral scaffold consisting of bone morphogenetic protein-2 (BMP-2)-loaded subchondral layer, fibroblast growth factor-18 (FGF-18)-loaded cartilage layer, and an interface layer that acted as a barrier to reduce the mutual interference of GFs, via cryogenic 3D bioprinting. BMP-2 could exert osteogenic effects for 14 days, and FGF-18 could exert chondrogenic effects for 21 days, demonstrating the time-controlled release function of BMP-2 and FGF-18. By further seeding discrete rat bone marrow mesenchymal stem cells (rBMSCs) and rBMSC microspheres, respectively, onto the subchondral layer and cartilage layer, the engineered cell-laden osteochondral tissue was constructed. The spatiotemporal release of BMP-2 and FGF-18 in the subchondral layer and cartilage layer promoted the osteogenic differentiation of discrete rBMSCs and chondrogenic differentiation of rBMSC microspheres in the subchondral layer and cartilage layer, respectively. In summary, by seeding rBMSCs with varied organizational morphologies in 3D-printed osteochondral scaffolds with a spatiotemporally controlled strategy, engineered osteochondral tissue with compartmentalized osteogenic/chondrogenic differentiation potent can be formed, displaying a facile and promising way to achieve desirable osteochondral tissue regeneration.

Structural Functions of 3D-Printed Polymer Scaffolds in Regulating Cell Fates and Behaviors for Repairing Bone and Nerve Injuries.

Tissue repair and regeneration, such as bone and nerve restoration, face significant challenges due to strict regulations within the immune microenvironment, stem cell differentiation, and key cell behaviors. The development of 3D scaffolds is identified as a promising approach to address these issues via the efficiently structural regulations on cell fates and behaviors. In particular, 3D-printed polymer scaffolds with diverse micro-/nanostructures offer a great potential for mimicking the structures of tissue. Consequently, they are foreseen as promissing pathways for regulating cell fates, including cell phenotype, differentiation of stem cells, as well as the migration and the proliferation of key cells, thereby facilitating tissue repairs and regenerations. Herein, the roles of structural functions of 3D-printed polymer scaffolds in regulating the fates and behaviors of numerous cells related to tissue repair and regeneration, along with their specific influences are highlighted. Additionally, the challenges and outlooks associated with 3D-printed polymer scaffolds with various structures for modulating cell fates are also discussed.

3D printed cellulose nanofiber/silica nanoparticle scaffolds for daytime radiative cooling

The high degree of modularity and miniaturization of nanoelectronic devices results in a significant increase in heat flux per unit area of electronic components. This can cause a rise in temperature, especially when used outdoors under direct sunlight conditions, which can negatively impact their operational stability and service life. Traditional radiators have limited effectiveness in outdoor sunlight conditions. Additionally, conventional heat sinks are often too large and heavy for miniature electronic devices. Therefore, finding an effective solution to cool electronics under sunlight conditions remains a challenge. Herein, we present an innovative solution to fabricate 3D-printed coolers for electronic devices based on the methyltrimethoxysilane/silica/cellulose nanofibers (MSC) ink. 3D printing technology enables the fabrication of radiative coolers with complex structures and efficient cooling performance as needed. The combination of CNFs and SiO₂ nanoparticles, coupled with the porous nature of the structure, enables the 3D-printed MSC scaffold to exhibit excellent solar reflectance and high mid-infrared (MIR) emissivity, thereby facilitating superior radiative cooling capabilities. During the daytime, it can efficiently reduce the temperature of electronic devices by 6.16 °C, thereby improving their operational efficiency and service life. Furthermore, the 3D-printed MSC scaffold exhibits superior mechanical properties due to the robust 3D frame structure formed by the ink components, which provides stability for the electronic device during operation. This study presents an innovative approach to developing electronic device coolers with excellent cooling performance, which is significant in promoting the reliability and stability of electronic devices.

A functional mineralized collagen hydrogel to promote angiogenic and osteogenic for osseointegration of 3D-printed titanium alloy microporous scaffolds

Bone defects, resulting from trauma, inflammation, tumors, and various other factors, affect both health and quality of life. Although autologous bone transplantation is the gold-standard treatment for bone defects, it has disadvantages such as donor site limitations, prolonged surgical durations, and potential complications, necessitating the development of alternative bone tissue engineering materials. In this study, we used 3D printing technology to fabricate porous titanium implants characterized by superior biocompatibility and mechanical properties. Sodium alginate (SA) and strontium ions (Sr2+) were integrated into mineralized collagen matrices (MCs) to develop strontium-functionalized alginate-mineralized collagen hydrogels (SAMs) with high mechanical strength and sustained metal ion release ability. SAMs were seamlessly incorporated into the porous structures of 3D-printed titanium scaffolds, establishing a novel organic–inorganic bioactive interface. This composite system exhibited high biocompatibility in vitro and increased the expression of genes important for osteogenic differentiation and angiogenesis. In a rabbit model of femoral defect, the titanium implants effectively promoted bone and vascular regeneration on their surface, highlighting their potential in facilitating bone–implant integration.

Biomimetic structural design and performance study of 3D-printed graded minimal surface bone scaffolds with enhanced bioactivity

Bone bionics and structural engineering have played a vital role in bone regeneration, with artificial scaffolds generating widespread interest. However, the mechanical properties and bone regeneration potential of biomimetic structures remain unclear. Herein, biodegradable polymer composites based on poly(butylene adipate-co-terephthalate)/poly(lactic acid) (PBAT/PLA) were 3D-printed into lattice structures as tissue engineering scaffolds. For structural design, graded diamond (D) minimal surfaces were proposed and designed to mimic the natural bone structure. The graded topologies were realized by designing gradient thickness either radially from center to edge or vertically from top to bottom. The mechanical performance of these graded samples displayed better load-carrying and energy absorption capacity than the uniform counterparts. No obvious damage was detected in the internal microstructure of the compressed samples using computed tomography. Subsequently, platelet-rich plasma (PRP), containing diverse cytokines, was loaded on the graded scaffolds. The PRP-loaded D-scaffold reported improved in vitro cell proliferation and osteoblast differentiation. Finally, femoral condyle defect repair results indicated that the PRP-loaded D-scaffold effectively promoted early-stage bone regeneration. Overall, this work provides insights into fabricating artificial scaffolds with bioactive factors and biomimetic lattice structures.

Fabrication of 3D-Printed Scaffolds with Multiscale Porosity.

3D printing is a promising technique for producing bone implants, but there is still a need to adjust efficiency, facilitate production, and improve biocompatibility. Porous materials have a proven positive effect on the regeneration of bone tissue, but their production is associated with numerous limitations. In this work, we described a simple method of producing polymer or polymer-ceramic filaments for 3D-printing scaffolds by adding micrometer-scale porous structures on scaffold surfaces. Scaffolds included polycaprolactone (PCL) as the primary polymer, β-tricalcium phosphate (β-TCP) as the ceramic filler, and poly(ethylene glycol) (PEG) as a porogen. The pressurized filament extrusion gave flexible filaments composed of PCL, β-TCP, and PEG, which are ready to use in fused filament fabrication (FFF) 3D printers. Washing of 3D-printed scaffolds in ethanol solution removed PEG and revealed a microporous structure and ceramic particles on the scaffold's surfaces. Furthermore, 3D-printed materials exhibit good printing precision, no cytotoxic properties, and highly impact MG63 cell alignment. Although combining PCL, PEG, and β-TCP is quite popular, the presented method allows the production of porous scaffolds with a well-organized structure without advanced equipment, and the produced filaments can be used to 3D print scaffolds on a simple commercially available 3D printer.

Recent Advances in 3D Printing of Smart Scaffolds for Bone Tissue Engineering and Regeneration.

The repair and functional reconstruction of bone defects resulting from severe trauma, surgical resection, degenerative disease, and congenital malformation pose significant clinical challenges. Bone tissue engineering (BTE) holds immense potential in treating these severe bone defects, without incurring prevalent complications associated with conventional autologous or allogeneic bone grafts. Three-dimensional (3D) printing technology enables control over architectural structures at multiple length scales and has been extensively employed to process biomimetic scaffolds for BTE. In contrast to inert and functional bone grafts, next-generation smart scaffolds possess remarkable ability to mimic the dynamic nature of native extracellular matrix (ECM), thereby facilitating bone repair and regeneration. Additionally, they can generate tailored and controllable therapeutic effects, such as antibacterial or antitumor properties, in response to exogenous and/or endogenous stimuli. This review provides a comprehensive assessment of the progress of 3D-printed smart scaffolds for BTE applications. It begins with an introduction to bone physiology, followed by an overview of 3D printing technologies utilized for smart scaffolds. Notable advances in various stimuli-responsive strategies, therapeutic efficacy, and applications of 3D-printed smart scaffolds are discussed. Finally, the review highlights the existing challenges in the development and clinical implementation of smart scaffolds, as well as emerging technologies in this field. This article is protected by copyright. All rights reserved.

Evaluating the Mechanical Strength of Three Dimensionally (3D) Printed Implants in Septorhinoplasty through Finite Element Analysis (FEA).

Autologous nasoseptal cartilage grafts are used to correct nasal asymmetry and deviation in rhinoplasty, but patients who have undergone multiple surgeries may have limited autologous cartilage tissue available. 3D-printed L-strut implants may address these challenges in the future, but their mechanical strength is understudied. Silk fibroin-gelatin (SFG), polycaprolactone (PCL), and polylactide (PLA) are bio-inks known for their strength. We present Finite Element Analysis (FEA) models comparing the mechanical strength of 3D-printed SFG, PCL, and PLA implants with nasoseptal cartilage grafts when autologous or allografts are not available. FEA models compared the stress and deformation responses of 3D-printed solid and scaffold implant replacements to cartilage. To simulate a daily force from overlying soft tissue, a unidirectional load was applied at the "keystone" region given its structural role and compared with native cartilaginous properties. 3D-printed solid SFG, PCL, and PLA and scaffold PCL and PLA models demonstrated lower deformations compared to cartilage. Solid SFG balanced strength and flexibility. The maximum stress was below all materials' yield stresses suggesting their deformations are unlikely permanent under a daily load. Our FEA models suggest that 3D-printed L-strut implants carry promising mechanical strength. Solid SFG's results mimicked cartilage's mechanical behavior. Thus, scaffold SFG merits further geometric optimization for potential use for cartilage substitution. 3D-printed septal cartilage replacement implants can potentially enhance surgical management of patients who lack available donor cartilage in select settings. Computational simulations can evaluate 3D-printed implant strength and their potential to replace septal cartilage in septorhinoplasty.

Electrospun and 3D printed scaffolds based on biocompatible polymers for 3D cultivation of glioblastoma cells in vitro

Additive manufacturing techniques capable of fabricating biocompatible scaffolds with a given submicron/micron/supramicron structure are of growing interest for biomedical applications, including tissue engineering and tumor biology studies. Here, we propose antisolvent 3D printing and electrospinning techniques to obtain biopolymer scaffolds with different structural, mechanical, and surface properties to compare the cultivation patterns of glioblastoma cells. We found that human G01 cells, derived from human glioblastoma tumor tissue, were able to colonize the scaffolds in a time-dependent manner; the cells showed high viability as confirmed by colorimetric MTT assay, confocal fluorescence microscopy, and scanning electron microscopy data. Electrospun collagen scaffolds (low porosity, thin 2.75±0.22 μm fibers, low Young's modulus 0.076±0.033 MPa) provided monolayer-like growth of G01 glioblastoma cells with dense cell-cell contacts, while 3D-printed PLGA scaffolds (high porosity, thick ∼150 µm fibers, high Young's modulus 18±2 MPa) stimulated glioblastoma-specific spindle-like morphology. All scaffolds were non-toxic to cells and maintained cell growth for at least 2 weeks. The developed scaffolds could be further used for tumor research as a 3D model of glioblastoma in vitro or for tissue engineering of brain injury.

Mechanical Characterisation of 3D-Printed Porous PLA Scaffolds with Complex Microarchitectures for Bone Tissue Engineering Applications

Bone transplantation remains the leading approach in addressing orthopaedic trauma or disease. In cases where this option is not viable, bone tissue engineering offers an alternative through the use of scaffolding. This approach involves the removal of damaged bone tissue and its replacement with porous scaffold structures to support the regeneration process. Recently, additive manufacturing has emerged as a promising technology for producing scaffold structures that satisfy the necessary performance criteria. In this study, PLA scaffolds with tortuous pore network designs were fabricated using fused deposition modelling. Scaffolds were fabricated with four different porosity values by changing the pore diameter in the range of 840–1732 µm. Sixteen specimens were tested under monotonic compression testing. Result shows the elastic moduli generated by each sample with 25%, 45%, 60% and 75% porosity: 545.21 ± 109.76, 446.82 ± 57.12, 312.55 ± 82.64 and 123.81 ± 23.95 MPa, respectively. Finite element simulation showed good correlation with experimental results, thereby effectively assessing the scaffold mechanical behaviour. Accordingly, the proposed finite element model can predict the mechanical behaviour of fabricated bone scaffolds accurately. The results demonstrate that the numerically predicted elastic modulus of complex scaffold is not closer to experimental outcomes in comparison with as-built samples. Overall, these findings suggest the potential of 3D-printed PLA scaffolds with tuneable porosity for cancellous bone replacement applications.

3D printed scaffolds with quercetin and vitamin D3 nanocarriers: In vitro cellular evaluation.

Increasing bone diseases and anomalies significantly challenge bone regeneration, necessitating the development of innovative implantable devices for effective healing. This study explores the potential of 3D-printed calcium phosphate (CaP) scaffolds functionalized with natural medicine to address this issue. Specifically, quercetin and vitamin D3 (QVD) encapsulated solid lipid nanoparticles (QVD-SLNs) are incorporated into the scaffold to enhance bone regeneration. The melt emulsification method is utilized to achieve high drug encapsulation efficiency (~98%) and controlled biphasic release kinetics. The process-structure-property performance of these systems allows more controlled release while maintaining healthy cell-material interactions. The functionalized scaffolds show ~1.3- and ~-1.6-fold increase in osteoblast cell proliferation and differentiation, respectively, as compared with the control. The treated scaffold demonstrates a reduction in osteoclastic activity as compared with the control. The QVD-SLN-loaded scaffolds show ~4.2-fold in vitro chemopreventive potential against osteosarcoma cells. Bacterial assessment with both Staphylococcus aureus and Pseudomonas aeruginosa shows a significant reduction in bacterial colony growth over the treated scaffold. These findings summarize that the release of QVD-SLNs through a 3D-printed CaP scaffold can treat various bone-related disorders for low or non-load-bearing applications.

Development and Evaluation of 3D-Printed PLA/PHA/PHB/HA Composite Scaffolds for Enhanced Tissue-Engineering Applications

Recently, tissue engineering has been revolutionised by the development of 3D-printed scaffolds, which allow one to construct a precise architecture with tailored properties. In this study, three different composite materials were synthesised using a combination of polylactic acid (PLA), polyhydroxyalkanoates (PHA), poly(3-hydroxybutyrate) (PHB) and hydroxyapatite (HA) in varying weight percentages. Morphological properties were evaluated by scanning electron microscopy showing a uniform distribution of HA particles throughout the matrix, indicating good compatibility between the materials. Furthermore, the printed scaffolds were tested under pressure using a load cell to examine mechanical strength. Scanning electron microscopy (SEM) analysis showed favorable dispersion, biological compatibility together with enhanced bioactivity within the PHB/PHA/PLA/HA composite matrixes. Thus, this paper demonstrates the successful design and implementation of these composite structures for tissue-engineering applications and highlights the effective development of biocompatible scaffold designs with improved functionality.

Delivery of letrozole-encapsulated niosomes via a 3D bioprinting gelatin–alginate scaffold for potential breast cancer treatment

3D printing technology is a powerful tool in scaffold engineering for biomedical applications, especially in anticancer activities and drug delivery. The present study developed a 3D-printed gelatin–alginate scaffold incorporating letrozole-loaded niosomes (Let/Nio@Gel-AL-SC) as a more effective drug delivery system. The findings showed that the fabricated niosomes appeared spherical. 3D-printed scaffolds exhibited biodegradability and sustained drug-release properties. The drug release from the scaffold was less prominent under acidic conditions than physiological ones. Cytotoxicity analysis showed that the engineered Let/Nio@Gel-AL-SC scaffold exhibited significant cytotoxicity against MCF-7 cancer cells. Gene expression analysis demonstrated a significant decrease in the expression of BCL2, CCND1, MMP2, and CDK4 genes and a notable increase in the expression of BAX and P53 genes, as well as the activity of Caspase 3/7 enzyme following treatment with Let/Nio@Gel-AL-SC. In addition, flow cytometry analysis revealed that Let/Nio@Gel-AL-SC significantly reduced necrosis and dramatically increased apoptosis. Also, the Let/Nio@Gel-AL-SC formulation exhibited a significantly greater increase in ROS values. The incorporation of letrozole-loaded niosomes into 3D printing gelatin/alginate scaffold has enhanced the efficacy of anticancer therapy. This is demonstrated by the sustained release of drugs, which indicates a promising potential for effective anticancer activity. Consequently, this combination holds promise as a potential future cancer therapy strategy.Graphical abstract

Creating a bionic scaffold via light-curing liquid crystal ink to reveal the role of osteoid-like microenvironment in osteogenesis

Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics, including viscoelasticity and liquid crystal (LC) state. Thus, integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair. Despite extensive research on viscoelasticity, the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials. Moreover, the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood. Here, we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink. By utilizing these LC scaffolds as 3D research models, we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation, while viscoelasticity operates via mechanotransduction pathways. Additionally, our investigation revealed a synergistic effect between LC state and viscoelasticity, amplifying cell-protein interactions and osteogenic mechanotransduction processes. Furthermore, the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing. Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis, offering valuable insights for the biomimetic design of bone repair scaffolds.