3D-printed Scaffolds Research Articles

A Functionalized 3D-Printed Ti6Al4V "Cell Climbing Frame" Inspired by Marine Sponges to Recruit and Rejuvenate Autologous BMSCs in Osteoporotic Bone Repair.

Osteoporosis, characterized by low bone mass and high fracture risk, challenges orthopedic implant design. Conventional 3D-printed Ti6Al4V scaffolds are mechanically robust but suffer from poor bone regeneration in osteoporotic patients due to stress shielding and cellular senescence. In this study, a functionalized 3D-printed Ti6Al4V "Cell Climbing Frame" is developed, aiming to adapt to the mechanical microenvironment of osteoporosis, effectively recruit and support the adhesion and growth of autologous bone marrow mesenchymal stem cells (BMSCs), while rejuvenating senescent cells for improved bone regeneration. Inspired by marine sponges, the processing accuracy limitations of selective laser melting (SLM) technology is broke through innovatively constructing a hierarchical porous structure with macropores and micropores nested within each other. Results demonstrate that the unique hierarchical porous scaffold reduces the elastic modulus, facilitates blood penetration, and enhances cell adhesion and growth. Further surface functionalization with E7 peptides and exosomes promotes the attraction and rejuvenation of BMSCs and boosts migration, proliferation, and osteogenic differentiation in vitro. In vivo, the functionalized "Cell Climbing Frame" accelerates bone repair in osteoporotic rats, while delaying surrounding bone loss, enabling robust multi-stage osseointegration. This innovation advances 3D-printed regenerative implants for osteoporotic bone repair.

Osteogenic Evaluation of 3D-printed PLA scaffolds Integrated with Khellin-loaded Chitosan-Alginate Sponges for Bone Tissue Engineering.

Bone tissue engineering (BTE) offers promising strategies for bone regeneration, yet the effective delivery of bioactive molecules remains a challenge. Khellin (KH), a plant-derived furanochromone, possesses various biological properties, though its potential in promoting osteogenesis has not been thoroughly investigated. In this study, 3D-printed polylactic acid (PLA) scaffolds were integrated with KH-loaded chitosan-alginate sponges (PLA/ALG/CS-KH) to facilitate controlled and sustained delivery of KH. Using sol-gel and freeze-drying techniques, KH was incorporated at varying concentrations (60, 70, and 80 μM) to enhance its bioavailability. Comprehensive physicochemical analyses demonstrated that KH incorporation did not alter the scaffolds' porosity, swelling capacity, protein adsorption, degradation rates, or biomineralization potential. In vitro studies revealed that the PLA/ALG/CS-KH scaffolds were biocompatible with mesenchymal stem cells and effectively promoted osteogenic differentiation, particularly at a concentration of 70 μM KH. These results suggest that PLA/ALG/CS-KH scaffolds have significant potential as osteoinductive platforms for BTE applications, providing a novel approach for enhancing bone regeneration through the sustained release of KH.

Abstract TMP77: Robotic-Guided Implantation of 3D-Printed Hydrogel Scaffolds to Enhance Axonal Regeneration and Functional Recovery After Stroke: A Novel Minimally Invasive Surgical Approach

Ischemic strokes often disrupt white matter (WM) microstructure, particularly affecting the corticospinal tract (CST) in the internal capsule (IC), leading to significant motor deficits. While evidence shows that axon sprouting occurs post-stroke, it often follows erratic paths, limiting functional recovery. Recent advances in 3D-printed hydrogel scaffolds have shown promise in guiding axon regeneration in spinal cord injury models. We hypothesize that implanting these scaffolds at white matter sites affected by stroke, aligned with CST fibers, will enhance functional axonal regeneration and motor recovery. Our aim is to develop and validate a precise and clinically applicable scaffold delivery system for future human studies. We have developed a novel, minimally invasive stereotaxic method for the precise deployment of 1.3 mm diameter scaffolds within the IC of non-human primates (NHPs). Our approach utilizes a clinically available stereotactic robot (ROSA, ZimmerBiomet) combined with a linear cannula system (AlphaOmega) to plan scaffold placement. Then, we attempted to deploy scaffolds devices into thermally coagulated lesions in NHPs (n=2) and simulated lesions within hydrogel phantoms (n=2). Post-implant MRI, co-registered with high-resolution diffusion tensor imaging were applied to check for scaffold placement accuracy (n=4). We further complement the scaffold placement method by using a novel neurosurgical microrobot (Robeauté) designed for navigation along 3D nonlinear curves, with accuracy confirmed by CBCT imaging in phantom tests. Our implantation methods accurately placed scaffolds in the intended locations and orientations, aligning with CST fibers in both phantom models and NHP brains. The deviation angle between the scaffold and CST fibers was 17.83° (SD 6.71°, n=3). The scaffolds were precisely positioned within the IC, validating our approach. Our robot-guided method accurately steered them to their intended position, demonstrating minimal errors in targeted white matter regions. The methods described are poised for clinical translation, potentially extending the applicability of scaffold technology for improving motor function post-stroke. We are preparing NHPs for behavioral and upper limb motor assessments to evaluate the impact of scaffold implantation on axon regeneration, recovery, and performance. This research aims to enhance our understanding of ischemic stroke and develop innovative therapies to restore motor function in patients.

Structurally sophisticated 3D-printed PCL-fibrin hydrogel meniscal scaffold promotes in situ regeneration in the rabbit knee meniscus.

A meniscus injury is a common cartilage disease of the knee joint. Despite the availability of various methods for the treatment of meniscal injuries, the poor regenerative capacity of the meniscus often necessitates resection, leading to the accelerated progression of osteoarthritis. Advances in tissue engineering have introduced meniscal tissue engineering as a potential treatment option. In this study, we established the size of a standardized meniscal scaffold using knee Magnetic Resonance Imaging (MRI) data and created a precise Polycaprolactone (PCL) scaffold utilizing 3-Dimensional (3D) printing technology, which was then combined with Fibrin (Fib) hydrogel to form a PCL-Fib scaffold. The PCL scaffold offers superior biomechanical properties, while the Fib hydrogel creates a conducive microenvironment for cell growth, supporting chondrocyte proliferation and extracellular matrix (ECM) production. Physical and chemical characterization, biocompatibility testing, and in vivo animal experiments revealed the excellent biomechanical properties and biocompatibility of the scaffold, which enhanced in situ meniscal regeneration and reduced osteoarthritis progression. In conclusion, the integration of 3D printing technology and the Fib hydrogel provided a supportive microenvironment for chondrocyte proliferation and ECM secretion, facilitating the in situ regeneration and repair of the meniscal defect. This innovative approach presents a promising avenue for meniscal injury treatment and advances the clinical utilization of artificial meniscal grafts.

Effect of 3D-Printed Polycaprolactone Scaffold With Powdery/Smooth Micromorphology on Local Immune Environments.

Selective laser sintering (SLS) has become a viable approach for producing biodegradable medical implants in various clinical applications. The resulting scaffolds typically exhibit a powdery microstructure, which may potentially impact the behavior of immune cells and immune responses in surrounding tissues. However, limited research has been conducted to understand the effect of surface morphology in SLS-fabricated scaffolds on local immune environments. This study aims to compare the effect of SLS-fabricated polycaprolactone (PCL) scaffolds with powdery and smooth surface morphologies on immune-related biological responses. Compared with those on the powdery micromorphology, RAW264.7 macrophages displayed greater dispersion and adopted a spread and elongated morphology on the scaffolds with smooth surface. The expression levels of arginase-1 and CD206 were found to be upregulated in macrophages adhering to the PCL scaffolds with smooth surface, accompanied by an augmented secretion of anti-inflammatory cytokines TGF-β and IL-10. Conversely, there was a decrease in the secretion of pro-inflammatory cytokines TNF-α and IL-12. When implanted invivo, the SLS-derived scaffolds were completely covered by host tissues, Withing increased collagen deposition, indicating good histocompatibility. At 1-week post-implantation, there was a significantly higher presence of M2-type macrophages surrounding the scaffold compared to M1 macrophages in both groups. By 3 weeks post-implantation, the overall level of macrophages had decreased in both groups. However, a significant higher level of M1 macrophages were observed in the powdery scaffold group. At the same time, the number of neutrophils around the powder scaffold increased significantly, demonstrating long-term local inflammatory responses. The results suggested that post-treated scaffolds with smooth surfaces can effectively reduce local inflammation, making them more suitable for clinical implantation.

3D printing of multifunctional hydrogel scaffolds based on recombinant collagen for bile duct repair

Bile duct injuries remain a significant clinical challenge following hepatobiliary surgeries. Recently, 3D-printed tubular scaffolds have shown promise as effective solutions for bile duct tissue repair. This study presents a novel bi-layered bile duct scaffold, fabricated using advanced three-dimensional printing technology. The inner layer of this scaffold is constructed from poly(ε-caprolactone) methacrylate (PCLMA), which imparts high mechanical strength. The outer layer is composed of biocompatible methacrylated recombinant type I collagen (rColMA) and ε-poly(L-lysine)-methacrylamide (EPLMA), providing excellent antibacterial properties. In addition, encapsulated interleukin-6-loaded liposomes (IL-6@Lip) are incorporated into the outer layer to further promote tissue regeneration. This innovative design creates an optimal microenvironment for the growth and differentiation of bone marrow mesenchymal stem cells (BMSCs) into bile duct-like cells. These differentiated cells contribute to bile duct tissue regeneration, as evidenced by the expression of key differentiation markers, including CK7, CK19, AQP1, AE2, and CX43. The rColMA/EPLMA/IL-6@Lip hydrogel in the outer layer of the scaffold significantly enhances BMSC proliferation and their differentiation into bile duct epithelial cells. Furthermore, in vivo experiments show that the PCLMA//rColMA/EPLMA/IL-6@Lip bi-layered scaffold does not induce bile stasis. This novel, pre-differentiated 3D-printed active scaffold offers valuable insights into bile duct tissue regeneration and replacement research.

Incorporating Insulin into Alginate-Chitosan 3D-Printed Scaffolds: A Comprehensive Study on Structure, Mechanics, and Biocompatibility for Cartilage Tissue Engineering

Incorporating Insulin into Alginate-Chitosan 3D-Printed Scaffolds: A Comprehensive Study on Structure, Mechanics, and Biocompatibility for Cartilage Tissue Engineering

Enhanced bone regeneration using mesenchymal stem cell-loaded 3D-printed alginate-calcium Titanate scaffolds: A Calvarial defect model study.

This study investigates the efficacy of a 3D-printed alginate composite scaffold enriched with calcium titanate nano powders and loaded with mesenchymal stem cells (MSCs) for bone regeneration in a calvarial defect model. Scaffolds (20 mm × 20 mm × 4.48 mm) with a slightly rough surface texture were fabricated using a bioprinter. A calvarial defect was created in the skulls of forty male Wistar rats, then divided into four treatment groups: empty defect, scaffold only, MSCs only, and MSC-seeded scaffold. After eight weeks, new bone formation was evaluated. The MSC-seeded scaffold group showed superior outcomes, including significantly higher bone mineral density (BMD), nearly complete defect closure in CT imaging, and enhanced histological results with newly formed bone and marrow cavities. Osteogenic gene markers (RunX2, OSX, COL1, BMP2, and OCN) and the angiogenic marker VEGF were notably upregulated, while the osteoclast-related gene RANKL was downregulated. These findings highlight the synergistic effect of the scaffold's osteoconductive properties and MSCs' regenerative potential. MSC-seeded alginate‑calcium titanate scaffold demonstrates promising results for critical-sized defect repair and may serve as a viable strategy for clinical bone tissue engineering applications.

Applications of biocompatible polymeric nanomaterials in three-dimensional (3D) scaffolds: Bacterial infections and diabetes.

Printed form of polymeric nanomaterials in formation, crosslinking, structure, properties, toxicity and biocompatibility refers to the application of nanotechnology and 3D printing techniques to fabricate polymeric nanomaterials with specific physicochemical and biomedical features. In this regard, applications of 3D printing techniques, specifically for production of 3D scaffold have received huge attention in diabetes and bacterial infections. This review has tried to address recent advances and challenges related to applications of biocompatible polymeric nanomaterials in 3D printing techniques to ameliorate bacterial infections and diabetes. The applications of metal/metal oxide such as silver, gold, zinc, and titanium dioxide, and polymeric nanoparticles can augment the antimicrobial and degradation characteristics of 3D-printed scaffolds. The rapid advancements in 3D bio-printed scaffolds, specifically by artificial intelligence (AI) present a transformative landscape for diabetes treatment, addressing the complex challenges associated with impaired wound healing and tissue regeneration in individuals with diabetes mellitus.

Chitosan microporous foam filled 3D printed polylactic acid-pearl macroporous scaffold: Dual-scale porous structure, biological and mechanical properties.

A bone scaffold with well-designed porous structure and material composition is essential for bone regeneration as it supports various biological functions. In this study, a dual-scale porous polylactic acid-pearl/chitosan (PLA-P/CS) scaffold was developed by integrating 3D printing and conventional techniques. An interconnected macroporous PLA-P scaffold with pore sizes ranging from 680 to 800 μm was fabricated using FDM 3D printing. Additionally, a microporous CS foam with pore sizes of 10-200 μm was prepared via freeze-drying within the macropores of the 3D-printed scaffold. The microporous CS foam enhanced the scaffold's hydrophilicity while preserving its favorable mechanical properties. Moreover, the dual-scale porous structure demonstrated improved biomineralization, due to its larger specific surface area and increased nucleation sites, along with the electrostatic adsorption provided by the amino and hydroxyl functional groups of chitosan. Furthermore, cell culture experiments revealed the dual-scale porous structure, and the effects of CS enhanced the cellular response of BMSCs. More importantly, a 12-week in vivo study on rat skull defect repair demonstrated that the dual-scale porous PLA-P/CS scaffold exhibited enhanced bone formation. These findings suggest that designing a graded porous structure and optimizing material composition can effectively enhance biological responses, thereby facilitating bone regeneration.

Rational design of 3D-printed scaffolds for breast tissue engineering using structural analysis.

Best cosmetic outcomes of breast reconstruction using tissue engineering techniques rely on the scaffold architecture and material, which are currently both to be determined. This study suggests an approach for a rational design of breast-shaped scaffold architecture, in which structural analysis is implemented to predict its stiffness and adjust it to that of the native tissue. This approach can help achieve the goal of optimal scaffold architecture for breast tissue engineering. 
Based on specifications defined in a preliminary implantation study of a non-rationally designed scaffold, and using analytical modeling and finite element analysis (FEA), we rationally designed a polycaprolactone (PCL) made, 3D-printed, highly porous, breast-shaped scaffold with a stiffness similar to the breast adipose tissue. This scaffold had an architecture of a double-shelled dome connected by pillars, with no bottom to allow direct contact of its fat graft with the host's blood vessels (Shelled Hemisphere Adaptive Design (SHAD)). To demonstrate the potential of the SHAD scaffold in breast tissue engineering, a proof-of-concept study was performed, in which SHAD scaffolds were embedded with human adipose derived mesenchymal stem cells (hAdMSCs), isolated from lipoaspirates, and implanted in Nod-Scid-Gamma (NSG) mouse model with a delayed fat graft injection. After 4 weeks of implantation, the SHAD implants were vascularized with a viable fat graft, indicating the suitability of the SHAD scaffold for breast tissue engineering. 
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3D-Printed PCL Scaffolds Loaded with bFGF and BMSCs Enhance Tendon-Bone Healing in Rat Rotator Cuff Tears by Immunomodulation and Osteogenesis Promotion.

Rotator cuff tears are the most common conditions in sports medicine and attract increasing attention. Scar tissue healing at the tendon-bone interface results in a high rate of retears, making it a major challenge to enhance the healing of the rotator cuff tendon-bone interface. Biomaterials currently employed for tendon-bone healing in rotator cuff tears still exhibit limited efficacy. As a promising technology, 3D printing enables the customization of scaffold shapes and properties. Bone marrow mesenchymal stem cells (BMSCs) have multidifferentiation potential and valuable immunomodulatory effects. The basic fibroblast growth factor (bFGF), known for its role in proliferation, has been reported to promote osteogenesis. These properties make them applicable in tissue engineering. In this study, we developed a 3D-printed polycaprolactone (PCL) scaffold loaded with bFGF and BMSCs (PCLMF) to restore the tendon-bone interface and regulate the local inflammatory microenvironment. The PCLMF scaffolds significantly improved the biomechanical strength, histological score, and local bone mineral density at regenerated entheses at 2 weeks postsurgery and achieved optimal performance at 8 weeks. Furthermore, PCLMF scaffolds facilitated BMSC osteogenic differentiation and suppressed adipogenic differentiation both in vivo and in vitro. In addition, RNA-seq showed that PCLMF scaffolds could regulate macrophage polarization and inflammation through the MAPK pathway. The implanted scaffold demonstrated excellent biocompatibility and biosafety. Therefore, this study proposes a promising and practical strategy for enhancing tendon-bone healing in rotator cuff tears.

Towards negative carbon footprint: carbon sequestration enabled manufacturing of coral-inspired tough structural composites

The increasing impacts of global warming necessitate effective mitigation strategies, with carbon sequestration emerging as a viable mid-term solution. Traditional methods focus on storing CO2 or converting it into liquid substances. However, natural processes like those found in corals demonstrate superior capabilities by transforming CO2 into robust, load-bearing solids with exceptional mechanical properties. Inspired by coral’s biomineralization, this study introduces an electrochemical manufacturing method that converts CO2 into calcium carbonate minerals around 3D-printed polymer scaffolds. This approach results in mineral-polymer composites characterized by extraordinary mechanical strength and fracture toughness, fire resistance, and crack repairability. These composites also offer structure-programmability and composition-reversibility. The scalable modular assembly of these composites supports the creation of larger-scale, load-bearing meso-structures. This manufacturing paradigm promotes negative carbon footprint practices, paving the way for sustainable engineering solutions and a more environmentally friendly future.

3D-Printed Polyurethane Scaffolds for Bone Tissue Engineering: Techniques and Emerging Applications

3D-Printed Polyurethane Scaffolds for Bone Tissue Engineering: Techniques and Emerging Applications

Fabrication and characterization of 3D-printed polymeric-based scaffold coated with bioceramic and naringin for a potential use in dental pulp regeneration (in vitro study).

3D-printed scaffolds loaded with healing directed agents could be employed for better treatment outcome in regenerative dentistry. The aim of this study was to fabricate and characterize simple 3D-printed poly lactic acid (PLA) scaffolds coated with nanoHydroxyapatite (nHA), Naringin (NAR), or their combination, and testing their morphological, chemical, mechanical, antibacterial, biocompatible and bioactive properties. Two variants pore sizes, 300 and 700 μm, of 3D-printed PLA disc scaffolds measuring (10 × 1 mm) were fabricated. These scaffolds were dip-coated with nHA, NAR, or both (nHA/NAR). Field emission scanning electron microscopy (FeSEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transforms infrared (FTIR), compressive and flexural strength testing was employed for optimizing pore size. Then, antibacterial activity against isolated Streptococcus mutans and Enterococcus faecalis, and cytotoxicity against normal human fibroblast were assessed. Additionally, appetite formation on scaffold surfaces was assessed after storage in simulated body fluid (SBF) for 14 days by further using FeSEM, EDX and XRD. FeSEM showed uniform structure for 3D-printed scaffolds in both pore size designs, and a consistent surface coating with nHA and NAR, which were further confirmed by EDX and FTIR. However, mechanical testing revealed statistical significant higher compressive and flexural strengths (p < .000) for 300 μm pore size scaffolds. Statistical significant antibacterial activities (p < .05) were also found with PLA/NAR, and PLA/nHA /NAR scaffolds in comparison with neat. The MTT assay revealed biocompatibility of PLA, nHA and NAR, with the combinations of the latter two working synergistically. Lastly, the formation of a calcium-phosphate appetite layer was recognized on the surface of PLA/nHA, PLA/nHA/NAR scaffold after being stored in SBF. 3D-printed, 300 μm pore size, PLA scaffold coated with a combination of nHA and NAR showed the best surface characteristics and improved mechanical, antibacterial and biocompatible properties for further investigation in regenerative studies.

Vat-Based 3D-Bioprinted Scaffolds from Photocurable Bacterial Levan for Osteogenesis and Immunomodulation.

Emerging techniques of additive manufacturing, such as vat-based three-dimensional (3D) bioprinting, offer novel routes to prepare personalized scaffolds of complex geometries. However, there is a need to develop bioinks suitable for clinical translation. This study explored the potential of bacterial-sourced methacrylate levan (LeMA) as a bioink for the digital light processing (DLP) 3D bioprinting of bone tissue scaffolds. LeMA was successfully synthesized, characterized, and used to fabricate 3D-bioprinted scaffolds with excellent printability and physicochemical properties. In vitro studies demonstrated superior cytocompatibility of 15% w/v LeMA gels compared to 20% gels. 15% LeMA gels supported osteogenic differentiation , as evidenced by alkaline phosphatase activity and mineral deposition by MC3T3 pre-osteoblasts. Importantly, the LeMA hydrogels positively modulated the macrophage phenotype, promoting the expression of the anti-inflammatory marker CD206. These findings suggest that 3D-printed LeMA scaffolds can create a favorable microenvironment for bone regeneration, highlighting their potential for tissue repair and regeneration applications.

Comparative analysis of solvent-based and solvent-free (melting) methods for fabricating 3D-printed polycaprolactone-hydroxyapatite composite bone scaffolds: physicochemical/mechanical analyses and in vitro cytocompatibility.

The study conducts a comparative analysis between two prominent methods for fabricating composites for bone scaffolds-the (solid) solvent method and the solvent-free (melting) method. While previous research has explored these methods individually, this study provides a direct comparison of their outcomes in terms of physicochemical properties, cytocompatibility, and mechanical strength. We also analyse their workflow and scalability potentials. Polycaprolactone (PCL) and hydroxyapatite (HA) composites were prepared using solvent (chloroform) and melting (180°C) methods, then 3D-printed using an extrusion-based 3D printer to fabricate scaffolds (8 × 8 × 4mm). Rheology, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), accelerated degradation, mechanical/compression test, wettability/contact angle, live/dead assay, and DNA quantification (Picogreen) assays were evaluated. The study finds that scaffolds made via the solid solvent method have higher mechanical strength and degradation rate as compared to those from the melting method, while both methods ensure adequate cytocompatibility and homogenous hydroxyapatite distribution, supporting their use in bone tissue engineering. This research investigates the utility of chloroform as a solvent for PCL composite in a direct comparison with the melting method. It also highlights the differences in workflows between the two methods and their scalability implications, emphasizing the importance of considering workflow efficiency and the potential for automation in scaffold fabrication processes for bone tissue engineering applications.

Optimizations of Placenta Extracellular Matrix-Loaded Silk Fibroin/Alginate 3D-Printed Scaffolds Structurally and Functionally for Bone Tissue Engineering.

Recent interest has been focused on extracellular matrix (ECM)-based scaffolds totreat critical-sized bone injuries. In this study, urea was used to decellularize and solubilize human placenta tissue. Then, different concentrations of ECM were composited with 8% alginate (Alg) and 12% silk fibroin (SF) for printing in order to produce a natural 3D construct that resembled bone tissue. The physical and biological features of the printed structures were evaluated entirely in vitro. Finally, a rat model was employed to examine the optimal 3D printed scaffold (5% ECM) as a bone transplant for the healing of cranial bone lesions. The present investigation demonstrated that decellularizing placental tissue fragments led to efficient removal of cell debris. In addition, a remarkable improvement in the printed scaffolds' mechanical and biological properties was observed by increasing the ECM concentration. The histology studies and real-time PCR results demonstrated the acceleration of bone regeneration in the bone lesions treated with 5%ECM-SF/Alg at 4 and 8 weeks after implantation. Overall, these results proved that the placental ECM-printed scaffolds could potentially construct biomimetic grafts to reconstruct significant bone defects and now promise to proceed with clinical studies.

Synergistic enhancement of angiogenesis and osseointegration in 3D-printed porous polyetheretherketone scaffolds using biomimetic coatings of bone morphogenetic protein-2/fibronectin.

This study explored a novel modification method for porous polyetheretherketone (PEEK) implants using a biomimetic coating to achieve synergistic enhancement of vascularization and bone regeneration. Inspired by the natural extracellular matrix (ECM) structure (consists of growth factors and matrix proteins), a biomimetic dual-factor coating capable of releasing bone morphogenetic protein-2 (BMP-2) and fibronectin (FN) was coated on the surface of 3D-printed porous PEEK scaffolds using polydopamine (PDA) as a binder. Experiments conducted with MC3T3-E1 cells or HUVECs in co-culture with scaffolds revealed that the biomimetic coating not only synergically promoted cell migration, adhesion and proliferation, but also enhanced angiogenesis and osteogenic differentiation simultaneously in vivo. The synergistic effect is attributed to the crosstalks between intracellular signaling pathways of FN and BMP-2, as well as the sustained release on account of their combination mitigates explosive release and degradation of BMP-2. Overall, this study designed a novel biomimetic coating modified PEEK scaffolds and confirmed the synergistic mechanism of the scaffolds on osteogenic differentiation and angiogenesis for the first time. These insights have significant implications for the clinical transformation of PEEK dental implants.

Surface engineering of 3D-printed polylactic acid scaffolds with polydopamine and 4-methoxycinnamic acid-chitosan nanoparticles for bone regeneration.

Bone remodeling, a continuous process of resorption and formation, is essential for maintaining skeletal integrity and mineral balance. However, in cases of critical bone defects where the natural bone remodeling capacity is insufficient, medical intervention is necessary. Traditional bone grafts have limitations such as donor site morbidity and availability, driving the search for bioengineered scaffold alternatives. The choice of biomaterial is crucial in scaffold design, as it provides a substrate that supports cell adhesion, proliferation, and differentiation. Poly-lactic acid (PLA) is known for its biocompatibility and biodegradability, but its hydrophobicity hinders cell attachment and tissue regeneration. To enhance PLA's bioactivity, we fabricated 3D-printed PLA scaffolds using fused deposition modelling. They were then surface-treated with NaOH to increase their reactivity, followed by polydopamine (PDA) and 4-methoxycinnamic acid (MCA)-loaded chitosan nanoparticle (nCS) coatings though polyelectrolyte complexation. Even though MCA, a polyphenolic, is known for its therapeutic properties, its osteogenic potential is not yet known. MCA treatment in mouse mesenchymal stem cells (mMSCs) promoted increased levels of Runx2 mRNA, a key bone transcription factor. Due to MCA's hydrophobic nature, nCS were used as carriers. The PLA/PDA/nCS-MCA scaffolds exhibited exceptional compressive strength and bioactivity. Biocompatibility tests confirmed that these scaffolds were non-cytotoxic to mMSCs. Overall, this study highlights the osteogenic potential of MCA and demonstrates the improved biocompatibility, bioactivity, wettability, and cell adhesion properties of the PDA/nCS-MCA-coated PLA scaffolds, positioning it as a promising material for bone tissue regeneration.