Mechanically robust and personalized silk fibroin-magnesium composite scaffolds with water-responsive shape-memory for irregular bone regeneration.

The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.

Composited silk fibroins ensured adhesion stability and magnetic controllability of Fe3O4-nanoparticle coating on implant for biofilm treatment.

Magnetic propulsion of nano-/micro-robots is an effective way to treat implant-associated infections by physically destroying biofilm structures to enhance antibiotic killing. However, it is hard to precisely control the propulsion in vivo. Magnetic-nanoparticle coating that can be magnetically pulled off does not need precise control, but the requirement of adhesion stability on an implant surface restricts its magnetic responsiveness. Moreover, whether the coating has been fully pulled-off or not is hard to ensure in real-time in vivo. Herein, composited silk fibroins (SFMA) are optimized to stabilize Fe3O4 nanoparticles on a titanium surface in a dry environment; while in an aqueous environment, the binding force of SFMA on titanium is significantly reduced due to hydrophilic interaction, making the coating magnetically controllable by an externally-used magnet but still stable in the absence of a magnet. The maximum working distance of the magnet can be calculated using magnetomechanical simulation in which the yielding magnetic traction force is strong enough to pull Fe3O4 nanoparticles off the surface. The pulling-off removes the biofilms that formed on the coating and enhances antibiotic killing both in vitro and in a rat sub-cutaneous implant model by up to 100 fold. This work contributes to the practical knowledge of magnetic propulsion for biofilm treatment.

Heterogeneous nucleation induced A. pernyi/B. mori silk fibroin coatings on AZ31 biometals with enhanced corrosion resistance, adhesion and biocompatibility.

Silk fibroin coatings on biomedical magnesium alloys have garnered significant attention due to their enhanced corrosion resistance and biocompatibility. However, the utilization of wild A. pernyi silk fibroin, known for its RGD sequence that facilitates tissue regeneration, presents a challenge for corrosion-resistant coatings on magnesium alloys due to its weak adhesion and high dissolution rate. In this study, we employed hexafluoroisopropanol as a solvent to blend A. pernyi silk fibroin with B. mori silk fibroin. The resulting blended fibroin coating at a 3:7 mass ratio exhibited a heterogeneous nucleation effect, enhancing ß-sheet content (32.3 %) and crystallinity (28.6 %). This improved ß-sheet promoted the "labyrinth effect" with an Icorr of 2.15 × 10-6 A cm-2, resulting in significantly improved corrosion resistance, which is two orders of magnitude lower than that of pure magnesium alloy. Meanwhile, the increased content of exposed serine in zigzag ß-sheet contributes to a higher adhesion strength. Cell cytotoxicity evaluation confirmed the enhanced cell adhesion and bioactivity. This work provides a facile approach for wild A. pernyi silk fibroin coatings on magnesium alloys with enhanced corrosion resistance, adhesion and biocompatibility.

Erratum: Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects.

[This corrects the article DOI: 10.1016/j.bioactmat.2023.11.001.].

Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects.

Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A three-dimensional (3D)-printed porous Ti6Al4V scaffold (3DTi) is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants, including a lower elasticity modulus, stronger bone-implant interlock, and larger drug-loading space. Simvastatin is a multitarget drug with anti-tumor and osteogenic potential; however, its efficiency is unsatisfactory when delivered systematically. Here, simvastatin was loaded into a 3DTi using a thermosensitive poly (lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and osteogenic effects. Newly constructed simvastatin/hydrogel-loaded 3DTi (Sim-3DTi) was comprehensively appraised, and its newfound anti-osteosarcoma mechanism was explained. Specifically, in a bone defect model of rabbit condyles, Sim-3DTi exhibited enhanced osteogenesis, bone in-growth, and osseointegration compared with 3DTi alone, with greater bone morphogenetic protein 2 expression. In our nude mice model, simvastatin loading reduced tumor volume by 59%-77 % without organic damage, implying good anti-osteosarcoma activity and biosafety. Furthermore, Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both in vivo and in vitro. Sim-3DTi is a promising osteogenic bone substitute for osteosarcoma-related bone defects, with a ferroptosis-mediated anti-osteosarcoma effect.

A Cell-Free Silk Fibroin Biomaterial Strategy Promotes In Situ Cartilage Regeneration Via Programmed Releases of Bioactive Molecules.

In situ tissue regeneration using cell-free biofunctional scaffolds has been extensively studied as a promising alternative strategy to promote cartilage repair. In this study, a cartilage-biomimetic silk fibroin (SF)-based scaffold with controlled sequential release of two bioactive molecules is developed. Transforming growth factor-ß1 (TGF-ß1) is initially loaded onto the SF scaffolds by physical absorption, which are then successively functionalized with bone marrow mesenchymal stem cells (BMSCs)-specific-affinity peptide (E7) via gradient degradation coating of Silk fibroin Methacryloyl (SilMA)/Hyaluronic acid Methacryloyl (HAMA). Such SF-based scaffolds exhibit excellent structural stability and catilage-like mechanical properties, thus providing a desirable 3D microenvironment for cartilage reconstruction. Furthermore, rapid initial release of E7 during the first few days, followed by slow and sustained release of TGF-ß1 for as long as few weeks, synergistically induced the recruitment of BMSCs and chondrogenic differentiation of them in vitro. Finally, in vivo studies indicate that the implantation of the biofunctional scaffold markedly promote in situ cartilage regeneration in a rabbit cartilage defect model. It is believed that this cartilage-biomimetic biofunctional SF-based scaffold with sequential controlled release of E7 and TGF-ß1 may have a promising potential for improved cartilage tissue engineering.

Extrusion Printed Silk Fibroin Scaffolds with Post-mineralized Calcium Phosphate as a Bone Structural Material.

Artificial bone materials are of high demand due to the frequent occurrence of bone damage from trauma, disease, and ageing. Three-dimensional (3D) printing can tailor-make structures and implants based on biomaterial inks, rendering personalized bone medicine possible. Herein, we extrusion-printed 3D silk fibroin (SF) scaffolds using mixed inks from SF and sodium alginate (SA), and post-mineralized various calcium phosphates to make hybrid SF scaffolds. The effects of printing conditions and mineralization conditions on the mechanical properties of SF scaffolds were investigated. The SF scaffolds from ~10 wt% SF ink exhibited a compressive modulus of 240 kPa, which was elevated to ~1600 kPa after mineralization, showing a significant reinforcement effect. Importantly, the mineralized SF 3D scaffolds exhibited excellent MC3T3-E1 cell viability and promoted osteogenesis. The work demonstrates a convenient strategy to fabricate SF-based hybrid 3D scaffolds with bone-mimetic components and desirable mechanical properties for bone tissue engineering.

The relationship between crosslinking structure and silk fibroin scaffold performance for soft tissue engineering.

Biologically active scaffolds with tunable mechano- and bio-performance remain desirable for soft tissue engineering. Previously, highly elastic and robust silk fibroin (SF) scaffolds were prepared via cryogelation. In order to get more insight into the role of ethylene glycol diglycidyl ether (EGDE) on the structure and properties of SF scaffolds, we investigated the fate of SF scaffolds with different usages of the crosslinking agent in vitro and in vivo. Although SF scaffolds with varied EGDE contents showed similar micro-morphology, increasing EGDE from 1 mmol/g to 5 mmol/g resulted in firstly increased and later decreased content of ß-sheet conformation, and linearly increased tensile modulus and decreased elasticity. The dual-crosslinked SF scaffolds with EGDE up to 5 mmol/g did not show in vitro cytotoxicity for NIH3T3 fibroblasts. In vivo subcutaneous implantation of SF scaffolds with <3 mmol/g EGDE displayed excellent degradation behavior and tissue ingrowth after 28 days of implantation. However, with ≥3 mmol/g EGDE, SF scaffolds exhibited obvious post-implantation foreign body reactions, probably associated with slow degradation due to excess chemical crosslinks and less mechanical compatibility. These results suggest that an appropriate dosage of crosslinking agent was critical to achieve balanced mechanical properties, degradability in vivo and immuno-properties of the SF scaffold platform for soft tissue engineering.

Applications of materials for dural reconstruction in pre-clinical and clinical studies: Advantages and drawbacks, efficacy, and selections.

The dura mater provides a barrier to protect the tissue underneath and cerebrospinal fluid. However, dural defects normally cause cerebrospinal fluid leakage and other complications, such as wound infections, meningitis, etc. Therefore, the reconstruction of dura mater has important clinical significance. Current dural reconstruction materials include: homologous, acellular, natural, synthetic, and composite materials. This review comprehensively summarizes the characteristics and efficacy of these dural substitutes, especially in clinical applications, including the advantages and drawbacks of those from different sources, the host tissue response in pre-clinical studies and clinical practice, and the comparison of these materials across different surgical procedures. Furthermore, the selections of materials for different surgical procedures are highlighted. Finally, the challenges and future perspectives in the development of ideal dural repair materials are discussed.

The effects of silk layer-by-layer surface modification on the mechanical and structural retention of extracellular matrix scaffolds.

Naturally derived extracellular matrix scaffolds can effectively promote tissue repair and regeneration due to their remarkable bioactivity. However, their rapid degradation leads to the decrease of mechanical retention and the failure of physical support in vivo which limit their applications. In this paper, we modified a classic extracellular matrix scaffold - small intestinal submucosa (SIS) - by a silk fibroin (SF) layer-by-layer (LbL) assembly to replace the existing chemical crosslinking methods for improving its mechanical and structural stability. Experimental results showed that the SF LbL surface functionalized SIS scaffold had tunable mechanical properties and degradation rate by adjusting the number of layers of the SF deposited on the surface. For biological responses, in vitro NIH3T3 fibroblast culture studies demonstrated that SF surface modification did not affect the excellent biocompatibility of the SIS. In vivo subcutaneous implantation results showed that the SF modification could effectively extend the residence time of the SIS in the body, and elicit a more moderate inflammatory response compared to the traditional glutaraldehyde chemical crosslinking. Furthermore, we found that SF modification could maintain the ability of bioactive components of the SIS to regulate the transformation of M1 into M2 in macrophages in vivo. This SF LbL modification strategy offers a green process for the development of high-performance extracellular matrix-based scaffolds with tunable biodegradability.

Controlled Cryogelation and Catalytic Cross-Linking Yields Highly Elastic and Robust Silk Fibroin Scaffolds.

Silk biomaterials with tunable mechanical properties and biological properties are of special importance for tissue engineering. Here, we fabricated silk fibroin (SF, from Bombyx mori silk) scaffolds from cryogelation under controlled temperature and catalytic cross-linking conditions. Structurally, the cryogelled scaffolds demonstrated a greater ß-sheet content but significantly smaller ß-sheet domains compared to that without chemical cross-linking and catalyst. Mechanically, the cryogelled scaffolds were softer and highly elastic under tension and compression. The 120% tensile elongation and >85% recoverable compressive strain were among the best properties reported for SF scaffolds. Cyclic compression tests proved the robustness of such scaffolds to resist fatigue. The mechanical properties, as well as the degradation rate of the scaffolds, can be fine-tuned by varying the concentrations of the catalyst and the cross-linker. For biological responses, in vitro rat bone mesenchymal stem cell (rBMSC) culture studies demonstrated that cryogelled SF scaffolds supported better cell attachment and proliferation than the routine freeze-thawed scaffolds. The in vivo subcutaneous implantation results showed excellent histocompatibility and tissue ingrowth for the cryogelled SF scaffolds. This straightforward approach of enhanced elasticity of SF scaffolds and fine-tunability in mechanical performances, suggests a promising strategy to develop novel SF biomaterials for soft tissue engineering and regenerative medicine.

Biomaterials research of China from 2013 to 2017 based on bibliometrics and visualization analysis.

OBJECTIVES: This study aims to evaluate the changes of development trends and research hotspots of biomaterials research from 2013 to 2017, which can identify the general information of papers and explore the changes of research content, thus providing perspectives for the development of biomaterials in China and other countries. METHODS: Data of the paper were retrieved from the Web of Science Core Collection, and then analyzed by the bibliometric and CiteSpace visualization analysis. RESULTS: It was found that a total of 3,839 related papers had been published from the year 2013 to 2017. The analysis of the articles showed that the annual quantity and quality of the articles in the biomaterials research have been increasing since 2013, and the Wang L / Chinese Academy of Sciences were the most productive author/institution. Meanwhile, the keywords "in vitro", "scaffold", "nanoparticle" , "mechanical property", and "biocompatibility" have the relatively higher frequency, and the keywords "apatite", "deposition", and "surface modification" have the strongest burst citation. CONCLUSIONS: After statistics and analysis, we found that biomaterials is a promising research field. The study may be helpful in understanding research trends in this field.