Bioactive Composite Scaffolds Research Articles

3D-printed magnesium-doped micro-nano bioactive glass composite scaffolds repair critical bone defects by promoting osteogenesis, angiogenesis, and immunomodulation

Magnesium ions play an important immune-regulatory role during bone repair. For this study, we prepared micro-nano bioactive glass (MNBG) containing magnesium, which can release magnesium, silicon, and calcium ions and has a positive impact on osteogenic differentiation and vascular regeneration. In this study, MgMNBG was compounded and combined with poly(lactic-co-glycolic acid (PLGA) and polycaprolactone (PCL) for 3D printing. Afterwards, the physicochemical properties and bone repair performance of the scaffolds were evaluated throughin vitroandin vivoexperiments. We also investigated the effects of MgMNBG on osteogenic differentiation, immune regulation, and vascular regeneration. The results showed that MgMNBG can inhibit inflammation and promote osteogenesis and angiogenesis by regulating macrophages. PLGA/PCL/MgMNBG scaffolds have good osteogenic and angiogenic effects, and the composite scaffolds have excellent bone repair performance and potential application value.

Laser powder bed fusion printed poly-ether-ether-ketone/bioactive glass composite scaffolds with dual-scale pores for enhanced osseointegration and bone ingrowth

Although poly-ether-ether-ketone (PEEK) implants hold significant medical promise, their bioinert nature presents challenges in osseointegration and bone ingrowth within clinical contexts. To mitigate these challenges, the present study introduces Diamond PEEK/bioactive glass (BG) composite scaffolds, characterized by macro/micro dual-porous structures, precisely fabricated via laser powder bed fusion (LPBF) technology. The findings indicate that an increase in BG content within these scaffolds significantly augments their hydrophilicity and hydroxyapatite formation capacities. Stress-strain curve analysis demonstrates reliable load-bearing stability across all scaffold types. In vitro assessments confirmed the non-cytotoxicity of PEEK/BG samples and demonstrated improved osteogenic differentiation and mineralization with increased BG incorporation. Further, in vivo experiments illustrated that the Diamond porous structure of these scaffolds facilitated bone growth, an effect notably amplified with higher BG content. Particularly in groups with 15 wt.% and 25 wt.% BG scaffolds, new bone formation was observed not only within the macropores of the Diamond structure but also within the micropores inside the scaffold rod, suggesting an almost seamless fusion with the new bone. This demonstrates the scaffolds’ effective osteointegration and bone ingrowth properties. This study conclusively established the effectiveness of Diamond-structured PEEK/BG composite scaffolds, fabricated via LPBF, in bone repair. It highlights the crucial role of BG in enhancing osteogenic potential through interaction with the macro/micro pores of the scaffold. Statement of significanceThis study addresses the bioinert nature of PEEK implants by developing Diamond-structured PEEK/bioactive glass (BG) composite scaffolds by laser powder bed fusion. The dual-porous macro/microstructure enhances hydrophilicity and hydroxyapatite formation, vital for bone regeneration. By adjusting the BG content, we controlled the melt viscosity and sintering rate, leading to the formation of beneficial microscale pores. These pores resolve the issue of ineffective bioactive fillers in previous LPBF-fabricated scaffolds, enhancing the osteogenic potential of BG and inducing superior bone ingrowth and osseointegration. In vitro and in vivo analyses show enhanced osteogenic differentiation, mineralization, and bone growth, underscoring the clinical potential of these scaffolds for bone repair.

Fabrication of 3D bioactive melt electrowriting composite scaffold with high osteogenic potential

A key challenge in using melt electrowriting (MEW) technology is incorporating large amounts of bioactive inorganic materials, such as hydroxyapatite (HA). In the present study, following optimization of the fabrication parameters, 40 %-HA (HA40) nanoparticles were pre-mixed into medical-grade polycaprolactone (PCL) and processed using the MEW (MEW) technique to mimic the structure and function of the natural extracellular matrix (ECM) for bone regeneration. The HA40 fibrous composite scaffolds showed continuous writing and obtained a well-connected and orderly stacked fibre with a small diameter size (67 ± 8.5 µm). A major result of the present study was the successful enrichment and accumulation of the HA particles, which mostly occurred on the MEW fibre external surfaces. This design allows for direct interfacial interaction with human periodontal ligament cells (hPDLCs). We systematically investigated the behaviour and function of hPDLCs on the HA40 composite scaffold, alongside parameters related to mineralization. The HA40 scaffold demonstrated significantly higher metabolic activity and enhanced expression of osteopontin compared to PCL-only scaffolds, as well as increased levels of ALP and COL1. The study’s findings demonstrate that bioactive composite scaffolds, incorporating 40 % HA into m-PCL via MEW, effectively enhance the biological response of the ECM and are promising for potential applications in bone regeneration.

A bioactive composite scaffold enhances osteochondral repair by using thermosensitive chitosan hydrogel and endothelial lineage cell-derived chondrogenic cell

Articular cartilage regeneration is a major challenge in orthopedic medicine. Endothelial progenitor cells (EPCs) are a promising cell source for regenerative medicine applications. However, their roles and functions in cartilage regeneration are not well understood. Additionally, thermosensitive chitosan hydrogels have been widely used in tissue engineering, but further development of these hydrogels incorporating vascular lineage cells for cartilage repair is insufficient. Thus, this study aimed to characterize the ability of EPCs to undergo endothelial–mesenchymal stem cell transdifferentiation and chondrogenic differentiation and investigate the ability of chondrogenic EPC-seeded thermosensitive chitosan-graft-poly (N-isopropylacrylamide) (CEPC-CSPN) scaffolds to improve healing in a rabbit osteochondral defect (OCD) model. EPCs were isolated and endothelial-to-mesenchymal transition (EndMT) was induced by transforming growth factor-β1 (TGF-β1); these EPCs are subsequently termed transdifferentiated EPCs (tEPCs). The stem cell-like properties and chondrogenic potential of tEPCs were evaluated by a series of in vitro assays. Furthermore, the effect of CEPC-CSPN scaffolds on OCD repair was evaluated. Our in vitro results confirmed that treatment of EPC with TGF-β1 induced EndMT and the acquisition of stem cell-like properties, producing tEPCs. Upon inducing chondrogenic differentiation of tEPCs (CEPCs), the cells exhibited significantly enhanced chondrogenesis and chondrocyte surface markers after 25 days. The TGF-β1-induced differentiation of EPCs is mediated by both the TGF-β/Smad and extracellular signal-regulated kinase (Erk) pathways. The CEPC-CSPN scaffold reconstructed well-integrated translucent cartilage and repaired subchondral bone in vivo, exhibiting regenerative capacity. Collectively, our results suggest that the CEPC-CSPN scaffold induces OCD repair, representing a promising approach to articular cartilage regeneration.

Bioactive polymer composite scaffolds fabricated from 3D printed negative molds enable bone formation and vascularization

Scaffolds for bone defect treatment should ideally support vascularization and promote bone formation, to facilitate the translation into biomedical device applications. This study presents a novel approach utilizing 3D-printed water-dissolvable polyvinyl alcohol (PVA) sacrificial molds to engineer polymerized High Internal Phase Emulsion (polyHIPE) scaffolds with microchannels and distinct multiscale porosity. Two sacrificial mold variants (250 µm and 500 µm) were generated using fused deposition modeling, filled with HIPE, and subsequently dissolved to create polyHIPE scaffolds containing microchannels. In vitro assessments demonstrated significant enhancement in cell infiltration, proliferation, and osteogenic differentiation, underscoring the favorable impact of microchannels on cell behavior. High loading efficiency and controlled release of the osteogenic factor BMP-2 were achieved, with microchannels facilitating release of the growth factor. Evaluation in a mouse critical-size calvarial defect model revealed enhanced vascularization and bone formation in microchanneled scaffolds containing BMP-2. This study not only introduces an accessible method for creating multiscale porosity in polyHIPE scaffolds but also emphasizes its capability to enhance cellular infiltration, controlled growth factor release, and in vivo performance. The findings suggest promising applications in bone tissue engineering and regenerative medicine, and are expected to facilitate the translation of this type of biomaterial scaffold. Statement of significanceThis study holds significance in the realm of biomaterial scaffold design for bone tissue engineering and regeneration. We demonstrate a novel method to introduce controlled multiscale porosity and microchannels into polyHIPE scaffolds, by utilizing 3D-printed water-dissolvable PVA molds. The strategy offers new possibilities for improving cellular infiltration, achieving controlled release of growth factors, and enhancing vascularization and bone formation outcomes. This microchannel approach not only marks a substantial stride in scaffold design but also demonstrates its tangible impact on enhancing osteogenic cell differentiation and fostering robust bone formation in vivo. The findings emphasize the potential of this methodology for bone regeneration applications, showcasing an interesting advancement in the quest for effective and innovative biomaterial scaffolds to regenerate bone defects.

Mechanical and in vitro study of 3D printed silk fibroin and bone-based composites biomaterials for bone implant application.

When treating orthopaedic damage or illness and accidental fracture, bone grafting remains the gold standard of treatment. In cases where this approach does not seem achievable, bone tissue engineering can offer scaffolding as a substitute. Defective and fractured bone tissue is extracted and substituted with porous scaffold structures to aid in the process of tissue regeneration. 3D bioprinting has demonstrated enormous promise in recent years for producing scaffold structures with the necessary capabilities. In order to create composite biomaterial inks for 3D bioprinting, three different materials were combined such as silk fibroin, bone particles, and synthetic biopolymer poly (ε-caprolactone) (PCL). These biomaterials were used to fabricate the two composites scaffolds such as: silk fibroin + bovine bone (SFB) and silk fibroin + bovine bone + Polycaprolactone (SFBP). The biomechanical, structural, and biological elements of the manufactured composite scaffolds were characterized in order to determine their suitability as a possible biomaterial for the production of bone tissue. The in vitro bioactivity of the two composite scaffolds was assessed in the simulated body fluids, and the swelling and degradation characteristics of the two developed scaffolds were analyzed separately over time. The results showed that the mechanical durability of the composite scaffolds was enhanced by the bovine bone particles, up to a specific concentration in the silk fibroin matrix. Furthermore, the incorporation of bone particles improved the bioactive composite scaffolds' capacity to generate hydroxyapatite in vitro. The combined findings show that the two 3D printed bio-composites scaffolds have the required mechanical strength and may be applied to regeneration of bone tissue and restoration, since they resemble the characteristics of native bone.

Three-dimensional printed silk fibroin and fenugreek based bio-composites scaffolds

When treating orthopaedic damage or illness and accidental fracture, bone grafting remains the gold standard of treatment. In cases where this approach doesn't seem achievable, bone tissue engineering can offer scaffolding as a substitute. Defective and fractured bone tissue is extracted and substituted with porous scaffold structures to aid in the process of tissue regeneration. Three-dimensional bioprinting has demonstrated enormous promise in recent years for producing scaffold structures with the necessary capabilities. In order to create composite biomaterial inks for three-dimensional bioprinting, four different materials were combined such as silk fibroin, bone particles (B), synthetic biopolymer poly (ε-caprolactone), and Fenugreek (F). These biomaterials were mixed together in certain proportion to develop a silk fibroin + bovine bone + polycaprolactone + fenugreek powder composites biomaterial which was later three-dimensional bioprinted to fabricated composite bio-scaffold. The biomechanical, structural, and biological elements of the manufactured composite scaffolds were characterized in order to determine their suitability as a possible biomaterial for the production of bone tissue. The in vitro bioactivity of the composite scaffolds was assessed in the simulated body fluids, and the swelling and degradation characteristics of the two developed scaffolds were analyzed separately over time. The results showed that the mechanical durability of the composite scaffolds was enhanced by the bovine bone particles, up to a specific concentration in the silk fibroin matrix. Furthermore, the incorporation of bone particles improved the bioactive composite scaffolds’ capacity to generate hydroxyapatite in vitro. The combined findings show that the three-dimensional printed bio-composites scaffolds have the required mechanical strength and may be applied to regeneration of bone tissue and restoration, since they resemble the characteristics of native bone.

Fabrication and characterization of a bioactive composite scaffold based on polymeric collagen/gelatin/nano β-TCP for alveolar bone regeneration

One strategy to correct alveolar bone defects is use of bioactive bone substitutes to maintain the structure of defect site and facilitate cells and vessels' ingrowth. This study aimed to fabricate and characterize the freeze-dried bone regeneration scaffolds composed of polymeric Type I collagen, nano Beta-tricalcium phosphate (β-TCP), and gelatin. The stable structures of scaffolds were obtained by thermal crosslinking and EDC/NHS ((1-ethyl-3-(3-dimethylaminopropyl) carbodiimide)/(N-hydroxysuccinimide)) chemical crosslinking processes. Subsequently, the physicochemical and biological properties of the scaffolds were characterized and assessed. The results indicated the bioactive composite scaffolds containing 10% and 20% (w/v) nano β-TCP exhibited suitable porosity (84.45 ± 25.43 nm, and 94.51 ± 14.69 nm respectively), a rapid swelling property (reaching the maximum swelling rate at 1 h), excellent degradation resistance (residual mass percentage of scaffolds higher than 80% on day 90 in PBS and Type I collagenase solution respectively), and sustained calcium release capabilities. Moreover, they displayed outstanding biological properties, including superior cell viability, cell adhesion, and cell proliferation. Additionally, the scaffolds containing 10% and 20% (w/v) nano β-TCP could promote the osteogenic differentiation of MC3T3-E1. Therefore, the bioactive composite scaffolds containing 10% and 20% (w/v) nano β-TCP could be further studied for being used to treat alveolar bone defects in vivo.

A Zinc Oxide Nanowire-Modified Mineralized Collagen Scaffold Promotes Infectious Bone Regeneration.

Bone infection poses a major clinical challenge that can hinder patient recovery and exacerbate postoperative complications. This study has developed a bioactive composite scaffold through the co-assembly and intrafibrillar mineralization of collagen fibrils and zinc oxide (ZnO) nanowires (IMC/ZnO). The IMC/ZnO exhibits bone-like hierarchical structures and enhances capabilities for osteogenesis, antibacterial activity, and bacteria-infected bone healing. During co-cultivation with human bone marrow mesenchymal stem cells (BMMSCs), the IMC/ZnO improves BMMSC adhesion, proliferation, and osteogenic differentiation even under inflammatory conditions. Moreover, it suppresses the activity of Gram-negative Porphyromonas gingivalis and Gram-positive Streptococcus mutans by releasing zinc ions within the acidic infectious microenvironment. In vivo, the IMC/ZnO enables near-complete healing of infected bone defects within the intricate oral bacterial milieu, which is attributed to IMC/ZnO orchestrating M2 macrophage polarization, and fostering an osteogenic and anti-inflammatory microenvironment. Overall, these findings demonstrate the promise of the bioactive scaffold IMC/ZnO for treating bacteria-infected bone defects.

Bioactive Conjugated Polymer-Based Biodegradable 3D Bionic Scaffolds for Facilitating Bone Defect Repair.

Bone defect regeneration is one of the great clinical challenges. Suitable bioactive composite scaffolds with high biocompatibility, robust new-bone formation capability and degradability are still required. This work designs and synthesizes an unprecedented bioactive conjugated polymer PT-C3 -NH2 , demonstrating low cytotoxicity, cell proliferation/migration-promoting effect, as well as inducing cell differentiation, namely regulating angiogenesis and osteogenesis to MC3T3-E1 cells. PT-C3 -NH2 is incorporated into polylactic acid-glycolic acid (PLGA) scaffolds, which is decorated with caffeic acid (CA)-modified gelatin (Gel), aiming to improve the surface water-wettability of PLGA and also facilitate to the linkage of conjugated polymer through catechol chemistry.A3D composite scaffoldPLGA@GC-PT is then generated. This scaffolddemonstrates excellent bionic structures with pore size of 50-300µm and feasible biodegradation ability. Moreover, it also exhibites robust osteogenic effect to promote osteoblast proliferation and differentiation in vitro, thus enabling the rapid regeneration of bone defects in vivo. Overall, this study provides a new bioactive factor and feasible fabrication approach of biomimetic scaffold for bone regeneration.

SLS 3D Printing To Fabricate Poly(vinyl alcohol)/Hydroxyapatite Bioactive Composite Porous Scaffolds and Their Bone Defect Repair Property.

Poly(vinyl alcohol) (PVA) exhibits a wide range of potential applications in the biomedical field due to its favorable mechanical properties and biocompatibility. However, few studies have been carried out on selective laser sintering (SLS) of PVA due to its poor thermal processability. In this study, in order to impart PVA powder the excellent thermal processability, the molecular complexation technology was performed to destroy the strong hydrogen bonds in PVA and thus significantly reduced the PVA melting point and crystallinity to 190.9 °C and 27.9%, respectively. The modified PVA (MPVA) was then compounded with hydroxyapatite (HA) to prepare PVA/HA composite powders suitable for SLS 3D printing. The final SLS 3D-printed MPVA/HA composite porous scaffolds show high precision and interconnected pores with a porosity as high as 68.3%. The in vitro cell culture experiments revealed that the sintered composite scaffolds could significantly promote the adhesion and proliferation of osteoblasts and facilitate bone regeneration, and the quantitative real-time polymerase chain reaction results further demonstrate that the printed MPVA/20HA scaffold could significantly enhance the expression levels of both early osteogenic-specific marker of alkaline phosphatase stain and runt-related transcription factor 2. Meanwhile, in in vivo experiments, it is encouragingly found that the resultant MPVA/20HA SLS 3D-printed part has an obvious effect on promoting the growth of new bone tissue as well as a better bone regeneration capability. This work could provide a promising strategy for fabrication of PVA scaffolds through SLS 3D printing, exhibiting a great potential for clinical applications in bone tissue engineering.

Tetracalcium phosphate/polycaprolactone composite scaffold: Mechanical reinforcement, biodegradability regulation and bioactivity induction

Polycaprolactone (PCL) is considered a potential biomaterial due to its good biocompatibility, but its slow degradability and insufficient mechanical properties limit its wide application in bone tissue engineering. Tetracalcium phosphate's (TTCP) good degradability and inherent high stiffness are expected to compensate for the aforementioned defects of PCL and endow it with good biological activity. This goal of this study was to obtain bioactive PCL composite scaffolds with tuneable degradation properties and good mechanical strength via selective laser sintering technology (SLS). Composite porous scaffolds with TTCP contents of 0%, 5%, 10%, 15%, 20%, and 25% were prepared, and the experimental results showed that the addition of TTCP significantly improved the mechanical properties of the scaffold. Notably, the tensile strength of the composite scaffold with 20% TTCP content reached 15.2 MPa, which was 2.9 times that of pure PCL, and the best flexural strength was found in the scaffold with 15% TTCP content (4.7 MPa). More importantly, the introduced TTCP not only achieved the effective pH regulation of the soaking solution and the promotion of biodegradation, but also provided the scaffold with good bioactivity and biocompatibility.

3D Bioprinting of a Bioactive Composite Scaffold for Cell Delivery in Periodontal Tissue Regeneration.

Hydrogels have been widely applied to the fabrication of tissue engineering scaffolds via three-dimensional (3D) bioprinting because of their extracellular matrix-like properties, capacity for living cell encapsulation, and shapeable customization depending on the defect shape. However, the current hydrogel scaffolds show limited regeneration activity, especially in the application of periodontal tissue regeneration. In this study, we attempted to develop a novel multi-component hydrogel that possesses good biological activity, can wrap living cells for 3D bioprinting and can regenerate periodontal soft and hard tissue. The multi-component hydrogel consisted of gelatin methacryloyl (GelMA), sodium alginate (SA) and bioactive glass microsphere (BGM), which was first processed into hydrogel scaffolds by cell-free 3D printing to evaluate its printability and in vitro biological performances. The cell-free 3D-printed scaffolds showed uniform porous structures and good swelling capability. The BGM-loaded scaffold exhibited good biocompatibility, enhanced osteogenic differentiation, apatite formation abilities and desired mechanical strength. The composite hydrogel was further applied as a bio-ink to load with mouse bone marrow mesenchymal stem cells (mBMSCs) and growth factors (BMP2 and PDGF) for the fabrication of a scaffold for periodontal tissue regeneration. The cell wrapped in the hydrogel still maintained good cellular vitality after 3D bioprinting and showed enhanced osteogenic differentiation and soft tissue repair capabilities in BMP2- and PDGF-loaded scaffolds. It was noted that after transplantation of the cell- and growth factor-laden scaffolds in Beagle dog periodontal defects, significant regeneration of gingival tissue, periodontal ligament, and alveolar bone was detected. Importantly, a reconstructed periodontal structure was established in the treatment group eight weeks post-transplantation of the scaffolds containing the cell and growth factors. In conclusion, we developed a bioactive composite bio-ink for the fabrication of scaffolds applicable for the reconstruction and regeneration of periodontal tissue defects.

Two-dimensional molybdenum disulfide/polymer-coated bioactive glass scaffolds for tissue engineering: Fabrication, structural, mechanical, bioactivity, and radiation interaction properties

Molybdenum disulfide (MoS2)-based nanostructures are widely used in environmental protection and biomedicine owing to their biological, physical, chemical, electrical, and mechanical properties. In this study, polycaprolactone (PCL)- and polylactide-co-glycolide (PLGA)-coated bioactive glass scaffolds containing MoS2 nanoparticles are prepared, and their usability in bone tissue engineering applications is evaluated. Borate bioactive glass scaffolds are fabricated using the replication method and coated with PCL or PLGA solutions (5 wt%) containing MoS2 (0.1, 0.2, 0.5, 1, and 2 wt%) nanoparticles. The structural and mechanical properties of the scaffolds and their bioactivity in simulated body fluids are investigated comprehensively. The ionization–radiation-shielding properties are investigated using Monte Carlo simulations. The results show that the polymer coating layer and presence of MoS2 nanoparticles in the polymer matrix improves the mechanical properties of the scaffolds. The addition of MoS2 nanoparticles to the structure increases the hydroxyapatite-forming ability of bioactive glass-based composites. Additionally, the prepared composite scaffolds exhibit high radiation-shielding ability owing to the presence of MoS2 nanoparticles embedded in the polymer matrix that shields the glass surface. Bioactive glass composite scaffolds containing MoS2 nanoparticles demonstrate promising potential for bone regeneration and radiation-shielding applications.

Biomimetic hydroxyapatite coating on the 3D-printed bioactive porous composite ceramic scaffolds promoted osteogenic differentiation via PI3K/AKT/mTOR signaling pathways and facilitated bone regeneration in vivo

• Bionic hierarchical scaffold fabricated by 3D-printing and surface mineralization. • The obtained biomimetic multi-structured scaffolds facilitate bone regeneration. • Regulation of cell fate in activated PI3K/AKT/mTOR signaling were confirmed. • Hydroxyapatite coating accelerates osseointegration and enhance bone-augmentation. • A two-step method enriches and guides the design of modified bone graft materials. The architecture and surface modifications have been regarded as effective methods to enhance the biological response of biomaterials in bone tissue engineering. The porous architecture of the implantation was essential conditions for bone regeneration. Meanwhile, the design of biomimetic hydroxyapatite (HAp) coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate osteogenesis. However, bioactive bio-ceramics such as β-tricalcium phosphate (β-TCP) and calcium silicate (CS) with superior apatite-forming ability were reported to present better osteogenic activity than that of HAp. Hence in this study, 3D-printed interconnected porous bioactive ceramics β-TCP/CS scaffold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction, and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells (mBMSCs) and the potential mechanisms were explored. The results indicated that HAp apatite coating enhanced cell proliferation, alkaline phosphatase (ALP) activity, and osteogenic gene expression. Furthermore, PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular functions. The present results demonstrated that the key molecules of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) were activated after the biomimetic hydroxyapatite coating were constructed on the 3D-printed ceramic scaffolds. Besides, the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor HY-10358. In vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone quality. These results suggest that biomimetic HAp coating constructed on the 3D-printed bioactive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration.

A PLA-tPU based magnesium ion incorporated CSH/nHA bioactive porous composite scaffold for critical bone defect repair

This study use freeze-drying technology prepared a PT-M-CN bioactive porous composite scaffold for bone defects repairing. Results showed it has a great potential to promote osteogenic differentiation and new bone regeneration.

Optimization of a concentrated growth factor/mesoporous bioactive glass composite scaffold and its application in rabbit mandible defect regeneration.

Maxillofacial bone defect repair and regeneration remains a tremendous challenge in the field of stomatology. However, the limited osteoinductivity of artificial materials and the high cost of bioactive agents restrain their clinical translation. This study aimed to construct an economical and efficient concentrated growth factor/mesoporous bioactive glass (CGF/MBG) composite scaffold for bone regeneration. The biochemical composition and biological effects of different forms of CGFs were systematically compared, and the results showed that CGF-conditioned medium effectively promoted proliferation, migration and osteogenesis of allogenic BMSCs. Gel phase CGF (gpCGF) exhibited superior bioactivity and osteoinductivity to liquid phase CGF (lpCGF) and liquid/gel mixed phase CGF (lgpCGF), and was further applied to construct CGF/MBG scaffolds. In vitro studies demonstrated that co-culture with gpCGF-conditioned medium further enhanced the biocompatibility of MBG, increasing cell adhesion and proliferation on the scaffold. On this basis, two compositing approaches to construct the scaffold by fibrin gel formation (CGF/FG/MBG) and freeze-drying (fdCGF/MBG) were applied, and the biological efficacy of CGFs was compared in vivo. In a rabbit mandibular defect model, higher osteogenic efficiency in in situ bone regeneration of CGF/FG/MBG composite scaffolds was proved, compared with fdCGF/MBG. Taken together, the CGF/FG/MBG composite scaffold is expected to be an efficient bone repairing therapy for clinical translation, and the CGF-composited scaffold using gpCGF and the fibrin gel formation method is a promising way to enhance the bioactivity and osteoinductivity of current clinical bone repairing materials, providing new thoughts on the development of future orthopedic biomaterials.

Engineering Three-Dimensional-Printed Bioactive Polylactic Acid Alginate Composite Scaffolds with Antibacterial and In Vivo Osteoinductive Capacity.

Although fused deposition modeling (FDM) has made it possible to create reproducible three-dimensional poly(lactic acid) (PLA) scaffolds, their efficacy for tissue engineering applications is limited by their lack of osteoinductive properties and antibacterial functions. Building on the success of the FDM constructs capable of supporting bone regeneration, we report here on the development of PLA scaffolds infused with sodium alginate cross-linked with both calcium and zinc divalent cations. Zn2+ cations were used to confer antibacterial and osteoinductive properties to enhance the performance of nontoxic PLA-alginate. Both the PLA and alginate polymers have been approved by the US Food and Drug Administration. In vivo bone regeneration capacity was demonstrated on a rabbit model by tomography and histological analysis. The scaffolds exhibited antibacterial activity against Gram-positive methicillin-resistant Staphylococcus epidermidis and Gram-negative Pseudomonas aeruginosa, while the control scaffolds could not resist the two microbial species tested. The scaffolds' physical properties were evaluated by field emission scanning electron microscopy with energy-disperse X-ray spectroscopy, Fourier transform infrared spectroscopy, water absorption, porosity measurements, and compression tests in dry and swollen states at body temperature. Their superior compressive properties, water uptake, and osteoinductive and antibacterial activities thus make them promising candidates for bone tissue regeneration.

Tailoring of mesoporous bioactive glass composite scaffold via thermal extrusion based 3D bioprinting and scrutiny on bone tissue engineering characteristics

In the recent years, mesoporous bioactive glass (MBG) based 3D printed scaffolds have been envisaged widely for bone tissue engineering potential. The earlier reports on 3D printed MBG based scaffolds for bone tissue engineering application are dedicated to pneumatic extrusion, which involves utilization of solvent and tedious process steps for preparation of bio ink. In order to overcome these limitations, the current work aims to develop 3D printed MBG based biomimetic composite scaffold via thermal extrusion process, which is devoid from solvent. It is well known that it is highly challenging to process pure MBG based inorganic/ceramic materials into 3D printed constructs due to lack of flexibility. Therefore, poly(caprolactone) (PCL) which exhibits bio inert nature towards formation of hydroxyapatite is used as the binder in order to impart flexibility during thermal extrusion process. The novelty of the current work lies in optimization of 3D printing parameters in order to fabricate MBG/PCL based composite construct, which mimics the natural bone composition with inorganic to organic ratio of 70:30 with hierarchical pore architecture and evaluation of its bone tissue engineering characteristics, which has not been documented earlier in the best of our knowledge. Through SBF studies, it is revealed that the 3D printed PCL/MBG composite scaffold helps in the formation of hydroxyapatite biomineral, which is lacking in the case of PCL scaffold. The presence of MBG in the PCL matrix is also found to support cellular proliferation and osteogenic differentiation, which is also reflected in terms of calcium mineralization and up regulation of osteogenic genes. This indicates that the 3D printed PCL/MBG composite scaffold mimicking the natural bone composition seems to hold promising potential for bone tissue engineering.

Carboxymethyl carrageenan immobilized on 3D-printed polycaprolactone scaffold for the adsorption of calcium phosphate/strontium phosphate adapted to bone regeneration

Three dimensional (3D) substrates based on natural and synthetic polymers enhance the osteogenic and mechanical properties of the bone tissue engineering scaffolds. Here, a novel bioactive composite scaffolds from polycaprolactone /kappa-carrageenan were developed for bone regeneration applications. 3D PCL scaffolds were fabricated by 3D printing method followed by coating with carboxymethyl kappa-carrageenan. This organic film was used to create calcium and strontium phosphate layers via a modified alternate soaking process in CaCl 2 /SrCl 2 and Na2HPO4 solutions in which calcium ions were replaced by strontium, with different amounts of strontium in the solutions. Various characterization techniques were executed to analyze the effects of strontium ion on the scaffold properties. The morphological results demonstrated the highly porous with interconnected pores and uniform pore sizes scaffolds. It was indicated that the highest crystallinity and compressive strength were obtained when 100% CaCl2 was replaced by SrCl2 in the solution (P-C-Sr). Incorporation of Sr onto the structure increased the degradation rate of the scaffolds. Mesenchymal stem cells (MSCs) culture on the scaffolds showed that Sr effectively improved attachment and viability of the MSCs and accelerated osteogenic differentiation as revealed by Alkaline phosphatase activity, calcium content and Real Time-Reverse transcription polymerase chain reaction assays.