Fibroin Composite Scaffolds Research Articles

Hydroxyapatite/Silk Fibroin Composite Scaffold with a Porous Structure and Mechanical Strength Similar to Cancellous Bone by Electric Field-Induced Gel Technology.

Repair and regeneration of bone tissue defects is a multidimensional process that has been highly challenging to date. The artificial bone scaffold materials, which play a core role, still face the conflict that a biofriendly porous structure will reduce the mechanical performance and accelerate degradation. Herein, a multistage porous structured hydroxyapatite (HA)/silk fibroin (SF) composite scaffold (e-HA/SF) was successfully constructed by cleverly utilizing electric field-induced gel technology. The results indicated that the prepared e-HA/SF scaffolds possess biomimetic hierarchical porous structures with a suitable porosity similar to that of cancellous bone. The HA nanocrystals were uniformly encapsulated in the three-dimensional space of the composite scaffold, thus endowing the e-HA/SF composite scaffolds with an enhanced mechanical performance. Notably, the maximum compression stress and Young's modulus of e-HA/SF-2 scaffolds can reach 24.66 ± 0.88 and 28.91 ± 3.19 MPa, respectively, which are equivalent to those of cancellous bone. Such mechanical performance enhancement was previously unattainable through conventional freeze-drying strategies. Moreover, the introduction of bioactive nano-HA can trigger the optimal cell response in both static and dynamic cell culture experiments in vitro. The e-HA/SF composite scaffold developed in this study can better balance the conflict between the porous structure and mechanical and degradation properties of porous scaffolds.

3D-printed nanohydroxyapatite/methylacrylylated silk fibroin scaffold for repairing rat skull defects

The repair of bone defects remains a major challenge in the clinic, and treatment requires bone grafts or bone replacement materials. Existing biomaterials have many limitations and cannot meet the various needs of clinical applications. To treat bone defects, we constructed a nanohydroxyapatite (nHA)/methylacrylylated silk fibroin (MASF) composite biological scaffold using photocurable 3D printing technology. In this study, scanning electron microscopy (SEM) was used to detect the changes in the morphological structure of the composite scaffold with different contents of nanohydroxyapatite, and FTIR was used to detect the functional groups and chemical bonds in the composite scaffold to determine the specific components of the scaffold. In in vitro experiments, bone marrow mesenchymal stem cells from SD rats were cocultured with scaffolds soaking solution, and the cytotoxicity, cell proliferation, Western blot analysis, Quantitative real-time PCR analysis, bone alkaline phosphatase activity and alizarin red staining of scaffolds were detected to determine the biocompatibility of scaffolds and the effect of promoting proliferation and osteogenesis of bone marrow mesenchymal stem cells in vitro. In the in vivo experiment, the skull defect was constructed by adult SD rats, and the scaffold was implanted into the skull defect site. After 4 weeks and 8 weeks of culture, the specific osteogenic effect of the scaffold in the skull defect site was detected by animal micro-CT, hematoxylin and eosin (HE) staining and Masson's staining. Through the analysis of the morphological structure of the scaffold, we found that the frame supported good retention of the lamellar structure of silk fibroin, when mixed with nHA, the surface of the stent was rougher, the cell contact area increased, and cell adhesion and lamellar microstructure for cell migration and proliferation of the microenvironment provided a better space. FTIR results showed that the scaffold completely retained the β -folded structure of silk fibroin, and the scaffold composite was present without obvious impurities. The staining results of live/dead cells showed that the constructed scaffolds had no significant cytotoxicity, and thw CCK-8 assay also showed that the constructed scaffolds had good biocompatibility. The results of osteogenic induction showed that the scaffold had good osteogenic induction ability. Moreover, the results also showed that the scaffold with a MASF: nHA ratio of 1: 0.5 (SFH) showed better osteogenic ability. The micro-CT and bone histometric results were consistent with the in vitro results after stent implantation, and there was more bone formation at the bone defect site in the SFH group.This research used photocurable 3D printing technology to successfully build an osteogenesis bracket. The results show that the constructed nHA/MASF biological composite material, has good biocompatibility and good osteogenesis function. At the same time, in the microenvironment, the material can also promote bone defect repair and can potentially be used as a bone defect filling material for bone regeneration applications.

Evaluation of rabbit adipose derived stem cells fate in perfused multilayered silk fibroin composite scaffold for Osteochondral repair.

Development of osteochondral tissue engineering approaches using scaffolds seeded with stem cells in association with mechanical stimulations has been recently considered as a promising technique for the repair of this tissue. In this study, an integrated and biomimetic trilayered silk fibroin (SF) scaffold containing SF nanofibers in each layer was fabricated. The osteogenesis and chondrogenesis of stem cells seeded on the fabricated scaffolds were investigated under a perfusion flow. 3-Dimethylthiazol-2,5-diphenyltetrazolium bromide assay showed that the perfusion flow significantly enhanced cell viability and proliferation. Analysis of gene expression by stem cells revealed that perfusion flow had significantly upregulated the expression of osteogenic and chondrogenic genes in the bone and cartilage layers and downregulated the hypertrophic gene expression in the intermediate layer of the scaffold. In conclusion, applying flow perfusion on the prepared integrated trilayered SF-based scaffold can support osteogenic and chondrogenic differentiation for repairing osteochondral defects.

Construction of ultrasonically treated collagen/silk fibroin composite scaffolds to induce cartilage regeneration

A novel tissue-specific functional tissue engineering scaffold for cartilage repair should have a three-dimensional structure, good biosafety and biological activity, and should be able to promote cartilage tissue regeneration. This study aimed to determine the effect of ultrasound-treated collagen/silk fibroin (Col/SF) composite scaffolds with good mechanical properties and high biological activity on cartilage repair. The characteristics of the scaffolds with different Col/SF ratios (7:3, 8:2, and 9:1) were determined by scanning electron microscopy, Fourier-transform infrared spectroscopy, and porosity, water absorption, and compression tests. In vitro evaluations revealed the biocompatibility of the Col/SF scaffolds. Results suggested that the optimal ratio of Col/SF composite scaffolds was 7:3. The Col/SF scaffolds induced adipose-derived stem cells to undergo chondrogenic differentiation under chondrogenic culture conditions. The efficiency of Col/SF scaffolds for cartilage regeneration applications was further evaluated using an in vivo model of full-thickness articular cartilage defects in New Zealand rabbits. The Col/SF scaffolds effectively promoted osteochondral regeneration as evidenced by macroscopic, histological, and immunohistochemical evaluation. The study demonstrates that ultrasound-treated Col/SF scaffolds show great potential for repairing cartilage defects.

Berberine oleanolic acid complex salt grafted hyaluronic acid/silk fibroin (BOA-g-HA/SF) composite scaffold promotes cartilage tissue regeneration under IL-1β caused stress

Since inflammatory cytokines cause stress to chondrocytes and the failure of cartilage defects repair with cartilage tissue engineering, it is necessary to develop a scaffold to maintain cartilage regeneration under inflammatory factors caused stress. Following a berberine-oleanolic acid (OA) complex salt (BOA) was grafted to hyaluronic acid (HA) to obtain water soluble BOA-g-HA, it mixed with silk fibroin (SF) to prepared 4 solutions, which contained 30 mg/mL SF and 0.75, 1.5, 2.25, and 3.0 mg/mL BOA-g-HA respectively. They were lyophilized to fabricate BOA-g-HA/SF-1, BOA-g-HA/SF-2, BOA-g-HA/SF-3, and BOA-g-HA/SF-4 composite scaffolds respectively. All prepared scaffolds displayed porous network structure and exhibited promising mechanical properties for tissue engineering applications. Among them, the BOA-g-HA/SF-3 composite scaffold showed the highest influence on maintaining chondrocytic phenotype of chondrocytes under IL-1β induced stress. Following SF, HA/SF, and BOA-g-HA/SF-3 composite scaffolds with seeded chondrocytes were treated with IL-1β induction for 1 week, specimens were incubated with cell culture medium for 3 week or were subcutaneously implanted into nude mice for 4 weeks. The results demonstrated that the BOA-g-HA/SF-3 composite scaffold promotes cartilage tissue regeneration in vitro and in vivo under IL-1β caused stress, suggesting that it can be potential applied for repairing cartilage defects in osteoarthritis patients.

Effect of Mechanical Loading on Bone Regeneration in HA/β-TCP/SF Scaffolds Prepared by Low-Temperature 3D Printing In Vivo.

It has been well demonstrated that a dynamic culture environment improves tissue-engineered bone formation in vitro, but little is known about how cyclical mechanical loading induced bone formation in scaffolds in situ. To mimic the organic and inorganic components and multilevel structure of a bony microenvironment, hydroxyapatite/β tricalcium phosphate/silk fibroin(HA/β-TCP/SF) composite scaffolds with macro- and micropores were fabricated in this study. The mechanical properties and structure of the scaffolds were adjusted based on the ratio of organic and inorganic components and three-dimensional (3D) printing parameters. Dynamic sinusoidal loading with different frequencies was applied to the composite scaffold. Mouse bone precursor cells MC3T3-E1 were seeded on the scaffolds, and the cell compatibility of the scaffolds was investigated by MTT, SEM, and HE. The effect of the loading on bone formation in the scaffold in situ was investigated in a rabbit tibia defect model. The scaffold showed viscoelasticity and hysteresis under dynamic sinusoidal loading with different frequencies. With an increase in HA/β-TCP, the stress and modulus of the scaffolds increased. MTT, SEM, and HE results showed that MC3T3-E1 cells could adhere and proliferate on the composite scaffolds. After loading in vivo, the quantity of newly formed bone and the bone volume fraction increased. Micro-CT, undecalcified Van Gieson (VG) staining, and fluorescent double-labeling results suggested that appropriate cyclical mechanical loading at frequencies of 1 and 10 Hz had positive effects on bone formation in situ and it may play a role in clinical bone defect repair.

Application of silk fibroin composite scaffold in bone tissue engineering

As a natural protein, silk protein has superior biocompatibility, biodegradability and mechanical properties, and can be used in different forms for bone tissue repair in bone tissue engineering as a good biomaterial. The treatment of bone defect has always been a serious challenge for orthopedic surgeons. However, the traditional treatment of bone defect is autologous bone and bone allograft, with limited source and secondary injury with sampling site; the allograft faces ethical problems, rejection, and viral transmission risk. Tissue engineering is an important means to solve tissue and organ defects. It establishes a three-dimensional space complex composed of cells and biological materials and fills the defects, so as to repair the effect Bone tissue scaffold with filim protein plays a huge role in orthopedics, and is expected to bring good news to more patients with bone diseases in the future. In this paper, we review the structural characteristics, biological properties and applications of filamentous proteins in bone tissue engineering.

Surface modification of silk fibroin composite bone scaffold with polydopamine coating to enhance mineralization ability and biological activity for bone tissue engineering

AbstractBone tissue engineering plays an important role in the treatment of bone defects. Finding suitable bone graft substitute scaffolds is still a major challenge. In this study, we combined silk fibroin‐octacalcium phosphate composite with silk fibroin by freeze‐drying technology, and the freeze‐dried scaffolds were further surface‐modified with self‐polymerization by using dopamine. The silk fibroin/octacalcium phosphate/polydopamine composite bone scaffold was successfully constructed. The composition and structure of the scaffolds were examined through Fourier infrared spectroscopy, X‐ray diffraction and scanning electron microscopy. The effects of different concentrations of polydopamine coatings on the porosity, swelling property, hydrophilicity, compressive strength, mineralization ability and biocompatibility of scaffolds were measured. The experimental results showed that the scaffolds had interconnected 3D network structure and polydopamine coating increased the compressive strength of SF scaffolds, delayed the degradation rate of scaffolds and enhanced the apatite deposition rate on the surface of scaffolds. The relative viability of cells increased with the rising of the concentration of coated polydopamine after co‐culture with MC3T3‐E1 cells. The polydopamine coating conferred the scaffolds excellent bioactivity. Therefore, silk fibroin/octacalcium phosphate/polydopamine composite scaffold may provide a new idea for bone tissue engineering.

Oxidized sodium alginate crosslinked silk fibroin composite scaffold for skin tissue engineering.

Engineering skin substitutes represent a prospective source of advanced therapy in repairing severe traumatic wounds. Sodium alginate (SA) and silk fibroin (SF) are natural biomaterials, which are widely used in tissue engineering and other fields because of their low price, high safety, and good biocompatibility. However, SA itself degrades slowly, its degradation mode is difficult to control, and the degradation products are difficult to remove from the body because of its high molecular weight. Therefore, the composite scaffolds were prepared by freeze-drying composite technology by using the Schiff base reaction between biocompatible SF and permeable oxidized sodium alginate (OSA). Sodium periodate was used as oxidant to modify SA. The results showed that higher oxidation degree of OSA could be obtained by increasing the proportion of oxidant, and the relative molecular weight of the oxidized products could also be reduced. The composite scaffolds were prepared by using sodium tetraborate as a crosslinking accelerator of the Schiff base reaction between OSA and SF. FT-IR confirmed that the Schiff base group appeared in the material. In vitro biodegradation experiments showed that the biodegradation of the composite scaffolds was controllable, and the cytocompatibility experiment showed that the composite scaffolds had good biocompatibility.

The incorporation of β-tricalcium phosphate nanoparticles within silk fibroin composite scaffolds for enhanced bone regeneration: An in vitro and in vivo study.

To investigate the osteogenesis of β-tricalcium phosphate nanoparticles-incorporated silk fibroin (SF/β-TCP) composite scaffolds, SF-based scaffolds with different β-TCP proportion (2/1, 1/1, and 1/2) were fabricated by freeze-drying technology in the present study. Structural and physicochemical properties of SF-based scaffolds were evaluated by using scanning electron microscope, X-ray diffraction, Fourier transformed infrared spectroscopy (ATR-FTIR) and transmission electron microscope. Biocompatibility and osteogenesis of SF/β-TCP scaffolds were investigated by using bone marrow mesenchymal stem cells (BMSCs). Eight New Zealand rabbits were selected, while four 8-mm-diameter calvarial defects were created in each rabbit to place SF/β-TCP scaffolds. The harvested specimens at 4 and 12weeks were used to evaluate the bone forming ability by micro-CT and histological examination. The results suggested incorporation of β-TCP displayed flake-like pore morphology with proper pore sizes. With the increasing proportion of β-TCP, composite scaffolds exhibited higher compressive strength, lower swelling ratio and degradation rate, as well as enhanced biomineralization capacity. Alkaline phosphatase activity and collagen type I expression levels of BMSCs were significantly increased in the presence of β-TCP nanoparticles. All composite scaffolds with different β-TCP proportion had good bone formation ability at 12weeks. Among them, SF/β-TCP (1/2) scaffold exhibited the favorable osteogenesis capability which had great potential for applications in bone regeneration.

Localized delivery of FTY-720 from 3D printed cell-laden gelatin/silk fibroin composite scaffolds for enhanced vascularized bone regeneration

Three-dimensional (3D) printing can construct products with accurate complex architecture. Engineered bone tissues that can promote vascularization and regulate directed differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) are considered as an ideal substitute the healing of bone for bone defects treatment. Herein, we fabricated a 3D printed BMSCs-laden scaffold using methacrylated gelatin and methacrylated silk fibroin (GelMA/SFMA) based bioinks along with localized sustained release of a small molecule drug fingolimod (FTY-720) for the synergistic interactions of vascularization and osteogenesis during bone repair. The GelMA/SFMA bioink showed significant advantages due to their tunable rheology, rapid thermal crosslinking, and improved shape fidelity following bioprinting. The in vitro experiments demonstrated that high cell viability of cells-laden constructs, while FTY-720-containing scaffolds significantly promoted migration and induced tube-like structure formation of human umbilical vein endothelial cells (HUVECs) as well as expressed high osteogenic-related genes expression of BMSCs. The implantation in a critical-size rat cranial defect model further revealed that FTY-720-loaded scaffolds significantly promoted vascularization and bone regeneration. Furthermore, scaffolds carrying BMSCs and FTY-720 were more osteogenic in vivo than scaffolds carrying BMSCs alone. Therefore, the constructed BMSCs-laden and FTY-720-loaded GelMA/SFMA scaffolds would be an ideal candidate with required structure and desired function for vascularization of bone regeneration.

A Naringin-loaded gelatin-microsphere/nano-hydroxyapatite/silk fibroin composite scaffold promoted healing of critical-size vertebral defects in ovariectomised rat

In this study, we investigated the effect of three-dimensional of naringin/gelatin microspheres/nano-hydroxyapatite/silk fibroin (NG/GMs/nHA/SF) scaffolds on repair of a critical-size bone defect of lumbar 6 in osteoporotic rats. In this work, a cell-free scaffold for bone-tissue engineering based on a silk fibroin (SF)/nano-hydroxyapatite (nHA) scaffold was developed. The scaffold was fabricated by lyophilization. Naringin (NG) was loaded into gelatin microspheres (GMs), which were encapsulated in the nHA/SF scaffolds. The materials were characterized using x ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. Moreover, the biomechanics, degradation, and drug-release profile of the scaffold were also evaluated. In vitro, the effect of the scaffold on the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) was evaluated. In vivo, at 3 months after ovariectomy, a critical-size lumbar defect was indued in the rats to evaluate scaffold therapeutic potential. A 3-mm defect in L6 developed in 60 SD rats, which were randomly divided into SF scaffold, nHA/SF scaffold, NG/nHA/SF scaffold, NG/GMs/nHA/SF scaffold, and blank groups (n = 12 each). At 4, 8, 12, and 16 weeks postoperatively, osteogenesis was evaluated by X-ray, micro-computed tomography, hematoxylin-eosin staining, and fast green staining, and by analysis of BMP-2, Runx2, and Ocn protein levels at 16 weeks. In our results, NG/GM/nHA/SF scaffolds exhibited good biocompatibility, biomechanical strength, and promoted BMSC adhesion, proliferation, and calcium nodule formation in vitro. Moreover, NG/GMs/nHA/SF scaffolds showed greater osteogenic differentiation potential than the other scaffolds in vitro. In vivo, gradual new bone formation was observed, and bone defects recovered by 16 weeks in the experimental group. In the blank group, limited bone formation was observed, and the bone defect was obvious. In conclusion, NG/GMs/nHA/SF scaffolds promoted repair of a lumbar 6 defect in osteoporotic rats. Therefore, the NG/GMs/nHA/SF biocomposite scaffold has potential as a bone-defect-filling biomaterial for bone regeneration.

Biomimetic Polydopamine-Modified Silk Fibroin/Curcumin Nanofibrous Scaffolds for Chemo-photothermal Therapy of Bone Tumor.

The simultaneous therapy of tumor recurrence and bone defects resulting from surgical resection of osteosarcoma is still a challenge in the clinic. Combination therapy based on a localized drug-delivery system shows great promise in the treatment of osteosarcoma. Herein, bifunctional polydopamine (PDA)-modified curcumin (CM)-loaded silk fibroin (SF) composite (SF/CM-PDA) nanofibrous scaffolds, which combined photothermal therapy with chemotherapy to synergistically enhance osteosarcoma therapy, were prepared by PDA coating of the SF/CM nanofibrous scaffolds fabricated by supercritical carbon dioxide (SC-CO2) technology. The PDA coating improved hydrophilicity and mechanical strength of the SF/CM scaffolds. The SF/CM-PDA scaffolds present good photothermal conversion capacity and excellent photostability. The low pH and near-infrared (NIR) irradiation could effectively accelerate release of CM in the SF/CM-PDA scaffolds. The in vitro anticancer results indicated that the biocompatible SF/CM-PDA scaffolds had a long-term, stable, and superior anticancer effect compared to pure CM. Furthermore, the SF/CM-PDA scaffolds significantly increased the growth inhibition of osteosarcoma MG-63 cells under NIR irradiation (808 nm and 1.3 W/cm2). Besides, the SF/CM-PDA scaffolds could enhance osteoblast MC3T3-E1 cell proliferation in vitro when the mass ratio of CM was 0.05–0.5%. This work has therefore demonstrated that the bifunctional SF/CM-PDA scaffolds provide a competitive strategy for local osteosarcoma therapy and bone regeneration.

Cover Image, Volume 138, Issue 44

The cover image created by Zheng Zhao and his colleagues shows an SEM micrography of sodium alginate (SA)/silk fibroin (SF) composite scaffolds with extracellular matrix (ECM)-like nanofibrous structures developed by supercritical CO2 technology. And the SA microparticles are embedded in the SF scaffolds. Increasing the SA content can improve the mechanical properties of the SF scaffolds and reduce the porosity of the SF scaffolds. Moreover, the SA microparticles can regulate the degradation rate of the SA/SF composite scaffolds. In addition, the SA/SF composite scaffolds exhibit higher L929 fibroblasts attachment and proliferation ability than the SF scaffolds. DOI: 10.1002/app.51421

Zn-substituted Mg2SiO4 nanoparticles-incorporated PCL-silk fibroin composite scaffold: A multifunctional platform towards bone tissue regeneration

Electrospun porous bone scaffolds are known to imitate the extracellular matrix very well and provide an environment through which the tissue formation is enhanced. Although polymeric scaffolds have a great potential in bone tissue regeneration, their weak bioactivity (bone bonding ability) and mechanical properties have left room for improvement. Therefore, the present study focused on the developing a ternary multifunctional platform composed of polycaprolactone (PCL)/silk fibroin (SF)/Zn-substituted Mg2SiO4 nanoparticles for bone tissue regeneration. This study is composed of two connected sections including synthesis and characterization of Mg(2-x)ZnxSiO4, x = 0, 0.5, 1, 1.5, 2 through surfactant-assisted sol-gel technique followed by incorporation of the nanoparticles into PCL/SF hybrid scaffold via electrospinning technique. The weight ratios of polymers and ceramic nanoparticles were optimized to reach desirable textural—porosity, pore size, and fiber diameter—and mechanical properties. Having optimized the ternary scaffold, it was then undergone different physical, chemical, and biological tests in vitro. A precise comparison study between the ternary (PCL/SF/ceramic nanoparticles), binary (PCL/SF), and pure PCL was made to shed light on the effect of each composition on the applicability of ternary scaffold. The overall results confirmed that the Mg1Zn1SiO4 nanoparticles-incorporated PCL/SF scaffold with fluorescence property was the one yielding the highest Young's modulus and desirable textural properties. The ternary scaffold showed improved biological properties making it a promising candidate for further studies towards bone tissue regeneration.

MSC-derived immunomodulatory extracellular matrix functionalized electrospun fibers for mitigating foreign-body reaction and tendon adhesion

Adhesion formation during tendon healing remains a severe problem in clinical practice. Multiple factors contribute to postoperative adhesion formation, and macrophage-driven inflammation is thought to be greatly involved in this process. We hypothesize that reducing macrophage-mediated inflammation in the injured tendon by regulating M1 to M2 macrophage polarization may effectively inhibit adhesion formation. Here, we developed an acellular immunomodulatory biomaterial consisting of an electrospun polycaprolactone/silk fibroin (PCL/SF) composite fibrous scaffold functionalized with mesenchymal stem cell (MSC)-derived extracellular matrix (ECM). To enhance the immunoregulatory potential of MSCs, we performed inflammatory licensing with IFN-γ to obtain immunomodulatory ECM (iECM). Proteomic analyses of MSCs and their secreted ECM components from different culture conditions revealed the MSC-ECM molecular signatures and the potential mechanism of ECM immunoregulation. Then, the immunoregulatory potential of the iECM-modified scaffold was evaluated in vitro and in vivo. Relative to the PCL/SF fibrous scaffold, the iECM-functionalized scaffold facilitated M2 macrophage polarization and inhibited the expression of multiple cytokines (IL-1β, IL-6, CXCL11, IL-10, IL-1R2, and TGF-β1) in vitro, strongly suggesting the immunosuppressive ability of iECM derived from inflammatory licensed MSCs. Consistent with the in vitro findings, the results of rat subcutaneous implantation indicated that a markedly lower foreign-body reaction (FBR) was obtained in the PCL/SF-iECM group than in the other groups, as evidenced by thinner fibrotic capsule formation, less type I collagen production and more M2-type macrophage polarization. In the rat Achilles tendon injury model, the PCL/SF-iECM scaffold greatly mitigated tendon adhesion with clear sheath space formation between the tendon and the scaffold. These data highlight the immunomodulatory potential of iECM-functionalized fibrous scaffolds to attenuate FBR by modulating M2 macrophage polarization, thereby preventing tendon adhesion. Statement of significanceElectrospun PCL/SF fibrous scaffolds functionalized with ECM secreted by MSCs stimulated by inflammatory factor IFN-γ was developed that combined physical barrier and immunomodulatory functions to prevent tendon adhesion formation. PCL/SF micro-nanoscale bimodal fibrous scaffolds prepared by emulsion electrospinning possess high porosity and a large pore size beneficial for nutrient transport to promote intrinsic healing; moreover, surface modification with immunomodulatory ECM (iECM) mitigates the FBR of fibrous scaffolds to prevent tendon adhesion. The iECM-functionalized electrospun scaffolds exhibit powerful immunomodulatory potency in vitro and in vivo. Moreover, the iECM-modified scaffolds, as an anti-adhesion physical barrier with immunomodulatory ability, have an excellent performance in a rat Achilles tendon adhesion model. MSC secretome-based therapeutics, as an acellular regenerative medicine strategy, are expected to be applied to other inflammatory diseases due to its strong immunoregulatory potential.

Usnic-Acid-Functionalized Silk Fibroin Composite Scaffolds for Cutaneous Wounds Healing.

Despite the progress in chronic wound treatment, antibacterial cutaneous scaffold with high efficiency in wound healing is still the hot spot in the field. In present study, a functionalized silk fibroin (SF) cutaneous scaffold incorporated with natural medicine usnic acid (UA) is investigated, in which UA is used as an antibacterial and wound-healing reagent. Via electrospinning, UA-SF mixture is fabricated into UA-SF composite scaffold (USCS), which is composed of uniform nanofibers with average diameters of around 360 ± 10nm. The interwoven nanofibers form mesh structure providing sufficient moisture permeability for scaffold. With methanol treatment, USCS presents improved mechanical properties and stability to protease XIV. In the presence of USCS, the growth rate of both Gram-positive and Gram-negative bacteria, including Staphylococcus aureus, Streptococci pyogenes, Escherichia coli, and Pseudomonas aeruginosa, is significantly inhibited in plate culture and suspension assays. In a cutaneous excisional mouse wound model, USCS presents a significant increase of wound closure rate, compared with pure SF scaffold and commercial dressing, Tegaderm Hydrocolloid 3M . The histological assessments further prove that USCS can enhance re-epithelialization, vascularization, and collagen deposition in wound site to promote the wound-healing process, which indicates the potential application of USCS in chronic wound treatment.

Enhancement of mechanical and biological performance on hydroxyapatite/silk fibroin scaffolds facilitated by microwave-assisted mineralization strategy

Three-dimensional (3D) porous hydroxyapatite/silk fibroin (HA/SF) composite scaffolds with good mechanical and biological performance, could provide a good cellular survival microenvironment for bone repair. However, coating HA efficiently and uniformly on SF scaffolds remains a challenge. In this study, the effects of microwave-assisted technology and biomineralization methods on the nanostructure, chemical composition and deposition efficiency of HA coating have been comparatively analyzed. Furthermore, the mechanical performance of the prepared 3D scaffolds was evaluated, and rat bone marrow mesenchymal stem cells were seeded on the 3D scaffolds to investigate their cytocompatibility and osteogenic differentiation capacities. The results indicate that microwave-assisted technology could improve the HA deposition efficiency to enhance the compressive strengths of 3D HA/SF scaffolds. Especially, when microwave-assisted technology is introduced in simulated body fluid mineralization process, the obtained 3D composite scaffold could trigger the best cellular response, including promoting cell adhesion, spreading, proliferation and osteogenic differentiation. This study may provide a promising strategy for constructing 3D porous scaffolds with excellent mechanical and biological performance for bone tissue engineering.

Development of functionally graded porous titanium/silk fibroin composite scaffold for bone repair

A composite scaffold comprising a silk fibroin (SF) sponge on functionally graded titanium (FG-Ti) was developed. The FG-Ti showed a radial graded structure similar to native long bone and better mechanical properties than those of homogeneous porous Ti with the same porosity. The microstructure of the composite scaffold was observed using scanning electron microscopy. The SF sponge filled in FG-Ti exhibited interconnected pore architecture, which could provide a suitable environment for cell attachment. The in vitro biocompatibility of the composite scaffolds was investigated using rat osteoblastic cells. Compared to FG-Ti, composite scaffolds exhibited an improved osteoblast adhesion and proliferation. These results suggest that the composite scaffold is a good candidate as a bone repair scaffold.

Solvent-Free Fabrication of Carbon Nanotube/Silk Fibroin Electrospun Matrices for Enhancing Cardiomyocyte Functionalities.

Cardiac tissue engineering holds great potential in regenerating functional cardiac tissues for various applications. The major strategy is to design scaffolds recapitulating the native cardiac microenvironment to enhance cell and tissue functionalities. Among various biomaterial systems, nanofibrous matrices with aligned morphologies and enhanced conductivity incline to induce the formation of oriented engineered cardiac tissues with enhanced functionalities. The challenge is to functionalize the scaffolds with conductive additives without influencing their biocompatibility. In this study, we developed a fully aqueous process for the fabrication of conductive carbon nanotube/silk fibroin (CNT/silk) electrospun scaffolds. The carbon nanotubes are well dispersed within the nanofibers, providing the scaffolds with enhanced conductivity and excellent biocompatibility for the culture of neonatal rat cardiomyocytes with improved cell spreading and enhanced expression of cardiac-specific proteins. Moreover, the aligned CNT/silk fibroin composite scaffolds exhibit abilities to guide the oriented organization of cardiac tissues and the biomimicking distribution of sarcomeres and gap junctions. The findings demonstrate the great potential of the CNT/silk scaffolds prepared through this aqueous processing method in supporting the formation of cardiac tissues with enhanced functionalities.