Flexible and high-strength bioactive glass fiber membrane for bone regeneration with the aid of alkoxysilane sol spinnability.

In this research, the spinnability of bioactive glass (BG) precursor solution was supplied by alkoxysilane sol with appropriate molar ratio of H2O/silicon (R) to prepare bioactive glass fiber membrane (BFM) using electrospinning (ES) technique. Alkoxysilane could form a linear or chain-like colloidal aggregation in hydrolysis-polycondensation with R = 2 or so, thereby exhibiting good spinnability. Therefore, the role of polymer binders could be largely replaced. Due to the significant decrease of polymer binder, the defects within the fibers are largely reduced and degree of fiber densification was improved after calcination, leading to BFM drastically enhanced strength and flexibility. The effect of R and calcination temperature on mechanical performance were investigated in detail. The tensile strength could reach the highest value 2.31 MPa with R = 2 and calcination at 700 °C. In addition, under this preparation condition, the BFM also possessed good flexibility with bending rigidity 37.7 mN. Furthermore, the great performance of promoting cell proliferation and osteogenesis could be observed from in vitro cellular experiment. The BFM calcined at 750 °C exhibited the best promoting osteogenic differentiation ability. The rat skull defect model revealed BFM could perform well in osteogenesis in vivo.

A self-assembled dynamic extracellular matrix-like hydrogel system with multi-scale structures for cell bioengineering applications.

Extracellular matrix (ECM) provides various types of direct interactions with cells and a dynamic environment, which can be remodeled through different assembly/degradation mechanisms to adapt to different biological processes. Herein, through introducing polyphosphate-modified hyaluronic acid and bioactive glass (BG) nano-fibril into a self-assembled hydrogel system with peptide-polymer conjugate, we can realize many new ECM-like functions in a synthetic polymer network. The hydrogel network formation is mediated by coacervation, followed by a gradual transition of peptide structure from  α-helix to ß-sheet. The ECM-like hydrogels can be degraded through a number of orthogonal mechanisms, including treatments with protease, hyaluronidase, alkaline phosphatase, and calcium ion. As 2D coating, the ECM-like hydrogels can be used to modify the planar surface to promote the adhesion of mesenchymal stromal cells, or to coat the cell surface in a layer-by-layer fashion to shield the interaction with the substrate. As ECM-like hydrogels for 3D cell culture, the system is compatible with injection and cell encapsulation. Upon incorporating fragmented electrospun bioactive glass nano-fibril into the hydrogels, the synergetic effects of soft hydrogel and stiff reinforcement nanofibers on recapitulating ECM functions result in reduced cell circularity in 3D. Finally, by injecting the ECM-like hydrogels into mice, gradual degradations over a time period of one month and high biocompatibility have been shown in vivo. The contribution of complex network dynamics and hierarchical structures to cell-biomatrix interaction can be investigated multi-dimensionally, as many mechanisms are orthogonal to each other and can be regulated individually. STATEMENT OF SIGNIFICANCE: A list of native ECM features has attracted the most interest and attention in the research of synthetic biomaterials. In this research, we have described a simple ECM-like hydrogel system in which the complex and elegant functions of native ECM can be recapitulated in a chemically defined synthetic system. The ECM-like hydrogel systems were developed to avoid undesired features of biological substances (e.g., ethical concerns, batch-to-batch variation, immunogenicity, and potential risk of contamination), as well as gaining new functions to facilitate bioengineering applications (e.g., 3D cell culture, injection, and high stability). To this end, we have developed an ECM-like hydrogel system and provide evidence that this purely synthetic biomaterial is a promising candidate for cell bioengineering applications.

Bio-inspired multifunctional collagen/electrospun bioactive glass membranes for bone tissue engineering applications.

Treatment of bone disease and disorders is often challenging due to its complex structure. Each year millions of people needs bone substitution materials with quick recovery from diseases conditions. Synthetic bone substitutes mimicking structural, chemical and biological properties of bone matrix structure will be very obliging and of copious need. In this work, we reported on the fabrication of bioinspired, biomimetic, multifunctional bone-like three-dimensional (3D) membranes made up of inorganic bioactive glass fibers matrixed organic collagen structure. The 3D structure is arranged as a stacked-layer similar to the order of apatite and neotissue formation. Comparative studies on collagen, collagen with hollow and solid bioactive glass fibers evidenced that, collagen/hollow bioactive glass is mechanically robust, has optimal hydrophilicity, simultaneously promotes bioactivity and in situ forming drug delivery. The 3D membrane displays outstanding mechanical properties apropos to the bioactive glass fibers arrangement, with its Youngs modulus approaching the modulus of cortical bone. The in vitro cell culture studies with fibroblast cells (3T3) on the membranes display enhanced cell adhesion and proliferation with the cell alignment similar to anisotropic cell alignment found in the native bone extracellular matrix. The membranes also support 3D cell culturing and exhibits cell proliferation on the membrane surface, which extends the possibility of its bone tissue engineering application. The alkaline phosphatase assessment and alizarin red staining of osteoblast cells (MG63) depicted an enhanced osteogenic activity of the membranes. Notable Runx2, Col-Type-1 mRNA, osteocalcin, and osteonectin levels were found to be significantly increased in cells grown on the collagen/hollow bioactive glass membrane. This membrane also promotes vascularization in the chick chorioallantoic membrane model. The results altogether evidence this multifunctional 3D membrane could potentially be utilized for treatment of bone defects.

In-vivo histocompatibility and osteogenic potential of biodegradable PLDLA composites containing silica-based bioactive glass fiber.

The purpose of this two-year study was to evaluate the histocompatibility and osteogenic properties of a composite material consisting of poly(l-co-d,l lactide) (PLDLA) and silica-based bioactive glass fibers in vivo. PLDLA and PLDLA/silica-based bioactive glass fibers pins were implanted into the erector spinae muscles and femurs of beagles. Muscle and bone tissue samples were harvested 6, 12, 16, 26, 52, 78, and 104 weeks after implantation. Histology analysis was used to assess the histocompatibility, angiogenesis, and bone-implant contact. Micro-computed tomography was used to evaluate bone formation around the pins. Immunohistochemistry and western blotting revealed the expression level of the osteogenesis-related proteins. Addition of bioactive glass was demonstrated to possess better histocompatibility and reduce the inflammatory reactions in vivo. Moreover, PLDLA/silica-based bioactive glass fibers pins were demonstrated to promote angiogenesis and increase osteogenesis-related proteins expression, and thus played a positive role in osteogenesis and osseointegration after implantation. Our findings indicated that a composite of PLDLA and silica-based bioactive glass fiber is a promising biodegradable material for clinical use.