Biomimetic Composite Scaffolds Research Articles

A Biomimetic Fibrous Composite Scaffold with Nanotopography-Regulated Mineralization for Bone Defect Repair.

The effective regeneration of large bone defects via bone tissue engineering is challenging due to the difficulty in creating an osteogenic microenvironment. Inspired by the fibrillar architecture of the natural extracellular matrix, we developed a nanoscale bioengineering strategy to produce bone fibril-like composite scaffolds with enhanced osteogenic capability. To activate the surface for biofunctionalization, self-adaptive ridge-like nanolamellae were constructed on poly(ε-caprolactone) (PCL) electrospinning scaffolds via surface-directed epitaxial crystallization. This unique nanotopography with a markedly increased specific surface area offered abundant nucleation sites for Ca2+ recruitment, leading to a 5-fold greater deposition weight of hydroxyapatite than that of the pristine PCL scaffold under stimulated physiological conditions. Bone marrow mesenchymal stem cells (BMSCs) cultured on bone fibril-like scaffolds exhibited enhanced adhesion, proliferation, and osteogenic differentiation in vitro. In a rat calvarial defect model, the bone fibril-like scaffold significantly accelerated bone regeneration, as evidenced by micro-CT, histological histological and immunofluorescence staining. This work provides the way for recapitulating the osteogenic microenvironment in tissue-engineered scaffolds for bone repair.

ROS-scavenging bioactive scaffold orchestrates bone regeneration for osteoporotic bone defect repair

The repair of osteoporotic bone defects, particularly those with irregular shapes, remains a significant challenge due to insufficient bone regeneration and an abnormal level of reactive oxygen species (ROS), which impairs the balance of bone remodeling. Materials that intrinsically regulate ROS to rebalance the activation of osteoblasts and osteoclasts represent a highly desirable alternative to current grafting strategies for the management of osteoporotic defects. Inspired by the tea polyphenols and natural extracellular matrix of bone tissue, a novel biomimetic composite scaffold, the epichlorohydrin-crosslinked hydroxyethyl cellulose/soy protein isolate/polydopamine-coated hydroxyapatite composite sponge (EHSS/PHA) scaffold was designed to orchestrate bone-forming bone marrow mesenchymal stem cells (BMSCs) and bone-resorbing osteoclasts for the rejuvenation of osteoporotic bone defect repair. Benefiting from the distinctive capabilities of the EHSS/PHA, including scavenging active oxygen and osteoinduction, we found that the EHSS/PHA could inhibit the formation of osteoclasts and promote osteogenesis of BMSCs by up-regulating the ratio of Opg/Rankl and activating the β-catenin signaling pathway in an oxidative stress environment. With its antioxidant ability, osteogenic, and self-deploying capability, EHSS/PHA effectively promoted the repair of tibial defects in osteoporotic rats by removing excess reactive oxygen species at the defect site. Taken together, this work presents the EHSS/PHA with multifunctional properties that provide new insight into osteoporotic bone defects.

Biomimetic Bone-Like Composite Hydrogel Scaffolds Composed of Collagen Fibrils and Natural Hydroxyapatite for Promoting Bone Repair.

Bone is a complex organic-inorganic composite tissue composed of ∼30% organics and ∼70% hydroxyapatite (HAp). Inspired by this, we used 30% collagen and 70% HAp extracted from natural bone using the calcination method to generate a biomimetic bone composite hydrogel scaffold (BBCHS). In one respect, BBCHS, with a fixed proportion of inorganic and organic components similar to natural bone, exhibits good physical properties. In another respect, the highly biologically active and biocompatible HAp from natural bone effectively promotes osteogenic differentiation, and type I collagen facilitates cell adhesion and spreading. Additionally, the well-structured porosity of the BBCHS provides sufficient growth space for bone marrow mesenchymal stem cells (BMSCs) while promoting substance exchange. Compared to the control group, the new bone surface of the defective location in the B-HA70+Col group is increased by 3.4-fold after 8 weeks of in vivo experiments. This strategy enables the BBCHS to closely imitate the chemical makeup and physical structure of natural bone. With its robust biocompatibility and osteogenic activity, the BBCHS can be easily adapted for a wide range of bone repair applications and offers promising potential for future research and development.

Indirect co-culture of osteoblasts and endothelial cells in vitro based on a biomimetic 3D composite hydrogel scaffold to promote the proliferation and differentiation of osteoblasts.

The field of orthopedics has long struggled with the challenge of repairing and regenerating bone defects, which involves a complex process of osteogenesis requiring coordinated interactions among different types of cells. The crucial role of endothelial cells and osteoblasts in bone vascularization and osteogenesis underscores the importance of their intimate interaction. However, efforts to bioengineer bone tissue have been impeded by the difficulty in establishing proper angiogenesis and osteogenesis in tissue structures. This study presents a novel approach to bone tissue engineering, involving a three-dimensional composite hydrogel scaffold composed of sodium alginate microspheres encapsulated in type I collagen. Using this scaffold, a three-dimensional indirect co-culture system was established for osteoblasts and endothelial cells to evaluate the osteogenic differentiation potential of osteoblasts. Results demonstrate that the non-contact co-culture system of endothelial cells and osteoblasts constructed by the composite hydrogel scaffold loaded with microspheres holds promise for bone tissue engineering. The innovative concept of an indirect co-culture system presents exciting prospects for conducting intercellular communication studies and offers a valuable in vitro tissue platform to investigate tissue regeneration.

DLP Fabrication of Multiple Hierarchical Biomimetic GelMA/SilMA/HAp Scaffolds for Enhancing Bone Regeneration.

Severe bone defects resulting from trauma and diseases remain a persistent clinical challenge. In this study, a hierarchical biomimetic microporous hydrogel composite scaffold was constructed by mimicking the hierarchical structure of bone. Initially, gelatin methacrylamide (GelMA) and methacrylic anhydride silk fibroin (SilMA) were synthesized, and GelMA/SilMA inks with suitable rheological and mechanical properties were prepared. Biomimetic micropores were then generated by using an aqueous two-phase emulsification method. Subsequently, biomimetic microporous GelMA/SilMA was mixed with hydroxyapatite (HAp) to prepare biomimetic microporous GelMA/SilMA/HAp ink. Hierarchical biomimetic microporous GelMA/SilMA/HAp (M-GSH) scaffolds were then fabricated through digital light processing (DLP) 3D printing. Finally, in vitro experiments were conducted to investigate cell adhesion, proliferation, and inward migration as well as osteogenic differentiation and vascular regeneration effects. In vivo experiments indicated that the biomimetic microporous scaffold significantly promoted tissue integration and bone regeneration after 12 weeks of implantation, achieving 42.39% bone volume fraction regeneration. In summary, this hierarchical biomimetic microporous scaffold provides a promising strategy for the repair and treatment of bone defects.

Internal and external co-induction pineal 3D printed scaffolds for bone and blood vessel regeneration

The precise structural design and reproducible manufacturing advantages of the 3D printed scaffold make it attract attention in clinical applications. However, the inability of scaffolds to achieve internal and external co-induced vascularized osteogenesis limits their application. After observing the ingenious and functionalized structural combination of "pinecone", this study prepared hydrogel microspheres encapsulating strontium ranelate (SrR)-dendrimer (PAMAM) as a functionalized "pine nuts" through microfluidic technology. The 3D-printed Polycaprolactone (PCL) scaffold was used as a framework in which hydrogel microspheres and a 3D-printed scaffold were cleverly combined. In this pinecone 3D-scaffold system, the slow release of SrR is beneficial to promote vascularization and osteogenic differentiation inside and outside the scaffold. Furthermore, the rat femoral defect model verified that the pinecone scaffold promoting the formation of internal vascular network, osteogenic differentiation and shortening the bone repair time in vivo. In summary, this pinecone degradable biomimetic composite scaffold with internal osteogenic differentiation and vascular activation functions has great potential for clinical demand in segmental bone defects.

Biomimetic collagen composite matrix-hydroxyapatite scaffold induce bone regeneration in critical size cranial defects

Although biomimetic scaffolds have been constructed to repair critical-size bone defects, the creation of composite scaffolds that can mimic the anisotropy of natural bone remains a major challenge. Herein, we have for the first time developed a biomimetic collagen composite matrix-hydroxyapatite (CCMH) scaffold, which highly resembles both the composition and the anisotropy hierarchical structure of natural bone. The CCMH scaffold was created through unidirectional freeze-casting and in situ peristaltic mineralization, resulting in uniformly distributed nano-hydroxyapatite on the porous collagen composite matrix (CCM) scaffold. The CCMH scaffold finely mimics the composition and anisotropic channel-like morphology of native bone, which exhibits high biocompatibility, excellent cellular activity and extraordinary osteogenic differentiation capability. Magnetic resonance imaging (MRI), micro-computed tomography (micro-CT) and histological analysis of rat models demonstrated that the CCMH scaffold significantly enhanced new bone formation and accelerated bone regeneration. The innovative unidirectional freezing-in situ peristaltic mineralization approach offers a robust technique for building biomimetic three-dimensional porous scaffolds with excellent biocompatibility and osteoinductivity, which show significant promise for use in bone repair and regeneration.

Double network composite scaffolds based on oxidized dextran/gelatin hydrogel and magnesium calcium phosphate cement

Magnesium is the fourth most abundant mineral in the human body and plays a significant role in bone growth and development. However, the precise role of magnesium ions is still considerably debated for bone tissue engineering. Here, the biomimetic composite (GelMCPC-x) scaffolds are produced by adding oxidized dextran/gelatin (OD/Gel) hydrogels and magnesium calcium phosphate cement (MCPC) that consisting of magnesium oxide (MgO), calcium dihydrogen phosphate, and β-tricalcium phosphate. The OD/Gel hydrogel provides the 3D network structure for the biomimetic scaffold. The addition of β-TCP affects the existence type of magnesium ions and MgO content in the biomimetic scaffolds. The MgO hydrated acts as an interacting site between inorganic and organic phases, while the sub-micron MgO particles function as a physical filling, both synergistic improving the compression strength of scaffolds through the chemisorption and physisorption. Our study suggests that the synergy between Gel and MgO actively controls for the nucleation site, and the calcium and magnesium ions provide the growth environment for apatite in vitro. When incorporated with 11 wt% of MgO, the GelMCPC-x composites have high compressive strength (5.3 MPa) and excellent osteogenic differentiation ability. This study provides guidelines for developing magnesium-based biomimetic scaffolds used in non-load-bearing bone.

Biodegradable silk fibroin scaffold doped with mineralized collagen induces bone regeneration in rat cranial defects

Compared with most nondegradable or slowly degradable bone repair materials, bioactive biodegradable porous scaffolds with certain mechanical strengths can promote the regeneration of both new bone and vasculature while the cavity created by their degradation can be replaced by the infiltration of new bone tissue. Mineralized collagen (MC) is the basic structural unit of bone tissue, and silk fibroin (SF) is a natural polymer with adjustable degradation rates and superior mechanical properties. In this study, a three-dimensional porous biomimetic composite scaffold with a two-component SF-MC system was constructed based on the advantages of both materials. The spherical mineral agglomerates of the MC were uniformly distributed on the surface and inside the SF skeleton, which ensured good mechanical properties while regulating the degradation rate of the scaffold. Second, the SF-MC scaffold had good osteogenic induction of bone marrow mesenchymal stem cells (BMSCs) and preosteoblasts (MC3T3-E1) and also promoted the proliferation of MC3T3-E1 cells. Finally, in vivo 5 mm cranial defect repair experiments confirmed that the SF-MC scaffold stimulated vascular regeneration and promoted new bone regeneration in vivo by means of in situ regeneration. Overall, we believe that this low-cost biomimetic biodegradable SF-MC scaffold with many advantages has some clinical translation prospects.

Interactions between Dental MSCs and Biomimetic Composite Scaffold during Bone Remodeling Followed by In Vivo Real-Time Bioimaging.

Oral-maxillofacial tumor removal can generate critical bone defects and major problems for patients, causing dysfunctionalities and affecting oral competencies such as mastication, swallowing, and breathing. The association of novel biomaterials and cell therapies in tissue engineering strategies could offer new strategies to promote osteomucosa healing. This study focused on the development of a bioengineered construct loaded with human dental follicle cells (MSCs). To increase the bioconstruct integration to the surrounding tissue, a novel and comprehensive approach was designed combining an injectable biomimetic hydrogel and dental stem cells (hDFMSCs) expressing luminescence/fluorescence for semi-quantitative tissue imaging in live animals. This in vivo model with human MSCs was based on an intramembranous bone regeneration process (IMO). Biologically, the biocomposite based on collagen/nanohydroxyapatite filled with cell-loaded osteopontin-fibrin hydrogel (Coll/nanoHA OPN-Fb) exhibited a high cellular proliferation rate, increased bone extracellular matrix deposition (osteopontin) and high ALP activity, indicating an early osteogenic differentiation. Thus, the presence of human OPN enhanced hDFMSC adhesion, migration, and spatial distribution within the 3D matrix. The developed 3D bioconstruct provided the necessary pro-regenerative effect to modulate the biological response, precisely fitting the bone defect with fine-tuned adjustment to the surrounding original structure and promoting oral osteomucosa tissue regeneration. We were also able to track the cells in vivo and evaluate their behavior (migration, proliferation, and differentiation), providing a glimpse into bone regeneration and helping in the optimization of patient-specific therapies.

Preparation and Synergistic Effect of Biomimetic Poly(lactic acid)/Graphene Oxide Composite Scaffolds Loaded with Dual Drugs.

To promote the bone repair ability of drug-loaded scaffolds, poly(lactic acid) (PLA)/graphene oxide (GO)/Salvianolic acid B (Sal-B)/aspirin (ASA) dual drug-loaded biomimetic composite scaffolds were prepared. The results showed that the addition of these two drugs delayed the gel formation of the composite system, but a biomimetic nanofiber structure could still be obtained by extending the gel time. The addition of Sal-B increased the hydrophilicity of the scaffold, while an increase in ASA reduced the porosity. Dual drug-loaded scaffolds had good haemocompatibility and synergically promoted the proliferation of MC3T3-E1 cells and enhanced alkaline phosphatase activity. Sustained-release experiments of the two drugs showed that the presence of ASA slowed the cumulative release of Sal-B, while Sal-B promoted the release of ASA. Kinetic modeling showed that the release of both drugs conforms to the Korsmeyer-Peppas model, but Sal-B conforms to the Fick diffusion mechanism and ASA follows Fick diffusion and carrier swelling/dissolution.

Anti-infective composite cryogel scaffold treats osteomyelitis and augments bone healing in rat femoral condyle

Bone and joint infections pose a serious challenge in the orthopedic medical condition which presents a major health care problem and economic burden to the patients. The current treatment strategies adopted have a very limited successful outcome in majority of the cases and need serious reconsiderations in terms of management, diagnosis and effective treatment approach. Herein, we have developed a composite cryogel scaffold from nanohydroxyapatite and collagen mimicking natural bone composition for the local delivery of antibiotic to treat osteomyelitis. The biomimetic and biodegradable antibiotic-loaded composite scaffold was found to be biocompatible with potent osteogenic capacity and anti-infective characteristics under in vitro conditions. Moreover, the anti-infective potency of the antibiotic-loaded composite cryogel was also evaluated in rat osteomyelitis model to cure the infection and promote bone healing. It was observed that anti-infective collagen-nanohydroxyapatite composite cryogel when loaded with bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA) could completely eradicate the infection in rat femoral condyle and simultaneously, accelerate bone healing at the dead space created during surgical procedures. The approach developed in this study is the development of biomimetic and bioactive composite carrier of antibiotics for the treatment of bone infection. The findings of this study insinuate that this antibiotic-loaded composite cryogel scaffold could potentially be used as an anti-infective biomaterial for the treatment of bone infections which will simultaneosuly promote bone healing at the dead space created during surgical procedures.

A silk fibroin/chitosan/nanohydroxyapatite biomimetic bone scaffold combined with autologous concentrated growth factor promotes the proliferation and osteogenic differentiation of BMSCs and repair of critical bone defects.

PurposeWith the goal of increasing the translational efficiency of bone tissue engineering for practical clinical applications, biomimetic composite scaffolds combined with autologous endogenous growth factors for repairing bone defects have become a current research hotspot. In this study, we prepared a silk fibroin/chitosan/nanohydroxyapatite (SF/CS/nHA) composite biomimetic scaffold and then combined it with autologous concentrated growth factor (CGF) to explore the effect of this combination on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the efficiency of repairing critical radial defects.MethodsThree kinds of SF/CS/nHA composite biomimetic scaffolds with mass fractions of 3%, 4%, and 5% were prepared by vacuum freeze-drying and chemical cross-linking methods, and the characteristics of the scaffolds were evaluated. In vitro, BMSCs were seeded on SF/CS/nHA scaffolds, and then CGF was added. The morphology and proliferation of BMSCs were evaluated by live-dead staining, phalloidin staining, and CCK-8 assays. ALP staining, alizarin red staining, cellular immunofluorescence, RT–PCR, and Western blotting were used to detect the osteogenic differentiation of BMSCs. In vivo, a rabbit radius critical bone defect model was constructed, and the SF/CS/nHA-BMSC scaffold cell complex combined with CGF was implanted. The effect on bone defect repair was evaluated by 3D CT scanning, HE staining, Masson staining, and immunohistochemistry.ResultsThe characteristics of 4% SF/CS/nHA were the most suitable for repairing bone defects. In vitro, the SF/CS/nHA combined CGF group showed better adhesion, cell morphology, proliferation, and osteogenic differentiation of BMSCs than the other groups (P < 0.05 for all). In vivo imaging examination and histological analysis demonstrated that the SF/CS/nHA scaffold combined with CGF had better efficiency in bone defect repair than the other scaffolds (P < 0.05 for all).ConclusionsA SF/CS/nHA composite biomimetic bone scaffold combined with autologous CGF promoted the proliferation and osteogenic differentiation of BMSCs in vitro and improved the repair efficiency of critical bone defects in vivo. This combination may have the potential for clinical translation due to its excellent biocompatibility.

Spatiotemporal Delivery of pBMP2 and pVEGF by a Core-Sheath Structured Fiber-Hydrogel Gene-Activated Matrix Loaded with Peptide-Modified Nanoparticles for Critical-Sized Bone Defect Repair.

The clinical translation of bioactive scaffolds for the treatment of large segmental bone defects remains a grand challenge. The gene-activated matrix (GAM) combining gene therapy and tissue engineering scaffold offers a promising strategy for the restoration of structure and function of damaged or dysfunctional tissues. Herein, a gene-activated biomimetic composite scaffold consisting of an electrospun poly(ε-caprolactone) fiber sheath and an alginate hydrogel core which carried plasmid DNA encoding bone morphogenetic protein 2 (pBMP2) and vascular endothelial growth factor (pVEGF), respectively, is developed. A peptide-modified polymeric nanocarrier with low cytotoxicity and high efficiency serves as the nonviral DNA delivery vector. The obtained GAM allows spatiotemporal release of pVEGF and pBMP2 and promotes osteogenic differentiation of preosteoblasts in vitro. In vivo evaluation using a critical-sized segmental femoral defect model in rats shows that the dual gene delivery system can significantly accelerate bone healing by activating angiogenesis and osteogenesis. These findings demonstrate the effectiveness of the developed dual gene-activated core-sheath structured fiber-hydrogel composite scaffold for critical-sized bone defect regeneration and the potential of cell-free scaffold-based gene therapy for tissue engineering.

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.

Biomimetic Graphene Oxide-Xanthan Gum-Hydroxyapatite Composite Scaffold for Bone Tissue Engineering

Biomimetic Graphene Oxide-Xanthan Gum-Hydroxyapatite Composite Scaffold for Bone Tissue Engineering

PCL/Si-Doped Multi-Phase Calcium Phosphate Scaffolds Derived from Cuttlefish Bone.

Increasing attention is focused on developing biomaterials as temporary scaffolds that provide a specific environment and microstructure for bone tissue regeneration. The aim of the present work was to synthesize silicon-doped biomimetic multi-phase composite scaffolds based on bioactive inorganic phases and biocompatible polymers (poly(ε-caprolactone), PCL) using simple and inexpensive methods. Porous multi-phase composite scaffolds from cuttlefish bone were synthesized using a hydrothermal method and were further impregnated with (3-aminopropyl)triethoxysilane 1–4 times, heat-treated (1000 °C) and coated with PCL. The effect of silicon doping and the PCL coating on the microstructure and mechanical and biological properties of the scaffolds has been investigated. Multi-phase scaffolds based on calcium phosphate (hydroxyapatite, α-tricalcium phosphate, β-tricalcium phosphate) and calcium silicate (wollastonite, larnite, dicalcium silicate) phases were obtained. Elemental mapping revealed homogeneously dispersed silicon throughout the scaffolds, whereas silicon doping increased bovine serum albumin protein adsorption. The highly porous structure of cuttlefish bone was preserved with a composite scaffold porosity of ~78%. A compressive strength of ~1.4 MPa makes the obtained composite scaffolds appropriate for non-load-bearing applications. Cytocompatibility assessment by an MTT assay of human mesenchymal stem cells revealed the non-cytotoxicity of the obtained scaffolds.

Preparation and biological properties of ZnO/hydroxyapatite/chitosan-polyethylene oxide@gelatin biomimetic composite scaffolds for bone tissue engineering

To imitate the composition of natural bone and further improve the biological property of the materials, ZnO/hydroxyapatite/chitosan-polyethylene oxide@gelatin (ZnO/HAP/CS-PEO@GEL) composite scaffolds were developed. The core-shell structured chitosan-polyethylene oxide@gelatin (CS-PEO@GEL) nanofibers which could form the intramolecular hydrogen bond and achieve an Arg-Gly-Asp (RGD) polymer were first prepared by coaxial electrospinning to mimic the extracellular matrix. To further enhance biological activity, hydroxyapatite (HAP) was grown on the surface of the CS-PEO@GEL nanofibers using chemical deposition and ZnO particles were then evenly distributed on the surface of the above composite materials using RF magnetron sputtering. The SEM results showed that chemical deposition and magnetron sputtering did not destroy the three-dimensional architecture of materials, which was beneficial to cell growth. The cell compatibility and proliferation of MG-63 cells on ZnO/HAP/CS-PEO@GEL composite scaffolds were superior to those on CS-PEO@GEL and HAP/CS-PEO@GEL composite scaffolds. An appropriate amount of ZnO sputtering could promote the adhesion of cells on the composite nanofibers. The structure of bone tissue could be better simulated both in composition and in the microenvironment, which provided a suitable environment for cell growth and promoted the proliferation of MG-63 cells. The biomimetic ZnO/HAP/CS-PEO@GEL composite scaffolds were promising materials for bone tissue engineering.

Fabrication of Antibacterial, Osteo-Inductor 3D Printed Aerogel-Based Scaffolds by Incorporation of Drug Laden Hollow Mesoporous Silica Microparticles into the Self-Assembled Silk Fibroin Biopolymer.

In this study, the novel biomimetic aerogel-based composite scaffolds through a synergistic combination of wet chemical synthesis and advanced engineering approaches have successfully designed. To this aim, initially the photo-crosslinkable methacrylated silk fibroin (SF-MA) biopolymer and methacrylated hollow mesoporous silica microcapsules (HMSC-MA) as the main constituents of the novel composite aerogels were synthesized. Afterward, by incorporation of drug-loaded HMSC-MA into the self-assembled SF-MA, printable gel-based composite inks are developed. By exploiting micro-extrusion-based three-dimensional (3D) printing, SF-MA-HMSC composite gels are printed by careful controlling their viscosity to provide a means to control the shape fidelity of the resulted printed gel constructs. The developed scaffold has shown a multitude of interesting biophysical and biological performances. Namely, thanks to the photo-crosslinking of the gel components during the 3D printing, the scaffolds become mechanically more stable than the pristine SF scaffolds. Also, freeze-casting the printed constructs generates further interconnectivity in the printed pore struts resulting in the scaffolds with hierarchically organized porosities necessary for cell infiltration and growth. Importantly, HMSC incorporated scaffolds promote antibacterial drug delivery, cellular ingrowth and proliferation, promoting osteoblastic differentiation by inducing the expression of osteogenic markers and matrix mineralization. Finally, the osteoconductive, -inductive, and anti-infective composite aerogels are expected to act as excellent bone implanting materials with an extra feature of local and sustained release of drug for efficient therapy of bone-related diseases.

Preparation and sustained-release properties of poly(lactic acid)/graphene oxide porous biomimetic composite scaffolds loaded with salvianolic acid B.

Biomimetic scaffolds loaded with drugs can improve the osteogenesis and neovascularisation of scaffolds. A series of PLA/GO/Sal-B drug-loaded scaffolds was prepared by thermally induced phase separation. The addition of Sal-B increased the diameter of the fibres, but the scaffold showed a porous nanofibrous structure after drug release. X-ray diffraction results showed that the addition of Sal-B did not affect the formation of the nanofibre biomimetic structure of the scaffold. FTIR results indicated a certain interaction between Sal-B and PLA/GO. Water absorption and porosity test results revealed that the scaffolds had good hydrophilicity and appropriate porosity. The addition of Sal-B was also conducive to the formation of sediments possibly due to the good water solubility of Sal-B itself. The prepared scaffolds had good blood compatibility and cytocompatibility, and a small additional amount of Sal-B could significantly promote cell proliferation and alkaline phosphatase activity. Their sustained release performance indicated that the biomimetic scaffolds had controlled the release of Sal-B. The kinetic model showed that the PLA/GO/Sal-B drug-loaded biomimetic scaffolds followed the diffusion mechanism.