Xianyan Yang

Bioactive glass-reinforced bioceramic ink writing scaffolds: sintering, microstructure and mechanical behavior

The densification of pore struts in bioceramic scaffolds is important for structure stability and strength reliability. An advantage of ceramic ink writing is the precise control over the microstructure and macroarchitecture. However, the use of organic binder in such ink writing process would heavily affect the densification of ceramic struts and sacrifice the mechanical strength of porous scaffolds after sintering. This study presents a low-melt-point bioactive glass (BG)-assisted sintering strategy to overcome the main limitations of direct ink writing (extrusion-based three-dimensional printing) and to produce high-strength calcium silicate (CSi) bioceramic scaffolds. The 1% BG-added CSi (CSi-BG1) scaffolds with rectangular pore morphology sintered at 1080 °C have a very small BG content, readily induce apatite formation, and show appreciable linear shrinkage (∼21%), which is consistent with the composite scaffolds with less or more BG contents sintered at either the same or a higher temperature. These CSi-BG1 scaffolds also possess a high elastic modulus (∼350 MPa) and appreciable compressive strength (∼48 MPa), and show significant strength enhancement after exposure to simulated body fluid-a performance markedly superior to those of pure CSi scaffolds. Particularly, the honeycomb-pore CSi-BG1 scaffolds show markedly higher compressive strength (∼88 MPa) than the scaffolds with rectangular, parallelogram, and Archimedean chord pore structures. It is suggested that this approach can potentially facilitate the translation of ceramic ink writing and BG-assisted sintering of bioceramic scaffold technologies to the in situ bone repair.

Trace element-incorporating octacalcium phosphate porous beads via polypeptide-assisted nanocrystal self-assembly for potential applications in osteogenesis.

The promising future of calcium phosphates (CaP) as a group of biomedical materials with a wide range of functions, might ultimately depend on tuning their composition and microstructure. However, the disorderly growth and aggregation of CaP nanocrystals limit their practical application. This paper reports a strategy for designing polypeptide/trace elements (TE), dual mediating the self-assembly of octacalcium phosphate (OCP) nanocrystals, with multilayered porous cross section and TE dilute doping. Intriguing advantages such as bead morphology, mesoporous structure, tunable diameter (20-1,000 μm) and TE contents, biodegradability and bioactivity are obtained. The microcomputerized-tomography reconstruction reveals an interconnective macroporous architecture and a void volume of over 49.02% for the nearly close-packed bead scaffolds. The specific surface area and average mesopore size are 89.73 m(2)g(-1) and 2.75 nm for the 180 μm diameter bead group, and those of 500 μm diameter beads are 130.17 m(2)g(-1) and 3.69 nm, respectively. It is demonstrated that the bead production mechanism is a multistep process including liquid-like precursor formation, nanocrystal nucleation and aggregation, aggregate combination and bead growth. Such a multilayer structure of TE-OCP porous beads would have adequate physical strength to maintain their shape, in contrast to the physical weakness of pure OCP hollow shell. The beads exhibit good biocompatibility and degradability and encourage bone mineralization in the early stage in vivo. This study demonstrates the feasibility of developing highly porous calcium phosphate giant beads via biomimetic self-assembly for direct application in reconstructive surgery and other widespread applications such as tissue engineering and drug delivery.

Simultaneous mechanical property and biodegradation improvement of wollastonite bioceramic through magnesium dilute doping.

The large-area bone defects in head (including calvarial, orbital, and maxillofacial bone) and segmental bone are attracting increased attention in a wide range of clinical departments. A key requirement for the clinical success of the bioactive ceramics is the match of the mechanical behavior of the implants with the specific bone tissue to be filled. This raises the question as to what design strategy might be the best indicators for the balance between mechanical properties and biological performances. Here we go beyond the traditional approaches that use phase conversion or biphasic hybrid; instead, we achieved a simultaneous enhancement of several mechanical parameters and optimalization of biodegradability by using a dilute doping of Mg in a single-phase wollastonite bioceramic. We show that the wollastonite ceramic can be rationally tuned in phase (α or β), mechanical strength (in compression and bending mode), elastic modulus (18-23GPa), and fracture toughness (>3.2MPam(1/2)) through the usage of Mg dopant introduced at precisely defined dilute concentrations (Mg/Ca molar ratio: 1.2-2.1%). Meanwhile, the dilute Mg-doped wollastonite ceramics are shown to exhibit good bioactivity in vitro in SBF but biodegradation in Tris is inversely proportional to Mg content. Consequently, such new highly bioactive ceramics with appreciable strength and toughness are promising for making specific porous scaffolds for enhancing large segmental bone defect and thin-wall bone defect repair.

Systematical Evaluation of Mechanically Strong 3D Printed Diluted magnesium Doping Wollastonite Scaffolds on Osteogenic Capacity in Rabbit Calvarial Defects

Wollastonite (CaSiO3; CSi) ceramic is a promising bioactive material for bone defect repair due to slightly fast degradation of its porous constructs in vivo. In our previous strategy some key features of CSi ceramic have been significantly improved by dilute magnesium doping for regulating mechanical properties and biodegradation. Here we demonstrate that 6 ~ 14% of Ca substituted by Mg in CSi (CSi-Mgx, x = 6, 10, 14) can enhance the mechanical strength (>40 MPa) but not compromise biological performances of the 3D printed porous scaffolds with open porosity of 60‒63%. The in vitro cell culture tests in vitro indicated that the dilute Mg doping into CSi was beneficial for ALP activity and high expression of osteogenic marker genes of MC3T3-E1 cells in the scaffolds. A good bone tissue regeneration response and elastoplastic response in mechanical strength in vivo were determined after implantation in rabbit calvarial defects for 6‒12 weeks. Particularly, the CSi-Mg10 and CSi-Mg14 scaffolds could enhance new bone regeneration with a significant increase of newly formed bone tissue (18 ~ 22%) compared to the pure CSi (~14%) at 12 weeks post-implantation. It is reasonable to consider that, therefore, such CSi-Mgx scaffolds possessing excellent strength and reasonable degradability are promising for bone reconstruction in thin-wall bone defects.

Enhancing in vitro bioactivity and in vivo osteogenesis of organic–inorganic nanofibrous biocomposites with novel bioceramics

Fabricating bioactive nanofibrous scaffolds from biodegradable polymers to mimic native tissue is an important approach in repairing bony defects. Silk fibroin (SF) may contribute to bone regeneration because of its excellent mechanical properties, slow degradability, and low osteoconductivity. A combination of bioceramic-polymer materials is generally used to provide an improved osteoconductive environment for bone healing. This study attempts developing for the first time an electrospun SF-based biocomposite system by introducing new bioceramics based on mesoporous bioactive glass/hydroxyapatite nanocomposite (MGHA). The addition of MGHA into the SF matrix could regulate the physicochemical properties and surface hydrophilicity, but induce weakened tensile properties as compared to pure SF. The excellent apatite-formation ability of a MGHA-introduced nanocomposite also improved the bioactivity of the composite. The biphasic composite increasingly degraded in PBS or enzyme solution in vitro compared with pure SF. In vivo evaluation of bone formation confirmed that SF/MGHA is more advantageous in bone reconstruction than the SF group for cranial bone defects. These results indicate the suitability of the SF/MGHA composite system in bone defects, demonstrating its potential application in bone tissue regeneration.

Bioactive glasses-incorporated, core-shell-structured polypeptide/polysaccharide nanofibrous hydrogels.

Although the synthetic hydrogel materials capable of accelerating wound healing are being developed at a rapid pace, achieving inorganic-organic hybrid at nanoscale dimension in nanofibrous hydrogels is still a great challenge because of its notorious brittleness and microstructural stability in wet state. Here, we developed a new nanofibrous gelatin/bioactive glass (NF-GEL/BG) composite hydrogel by phase separation method and followed by arming the nanofibers network with counterionic chitosan-hyaluronic acid pairs for improving microstructural and thermal integrity. We achieve this feature by carrying an optimal balance of charges that allows the inorganic ion release in aqueous solution without minimal structure collapse. Therefore, such NF-GEL-based, polysaccharide-crosslinked bioactive hydrogel could afford a close biomimicry to the fibrous nanostructure and constituents of the hierarchically organized natural soft tissues to facilitate chronic, nonhealing wound treatment.

Bone regeneration in 3D printing bioactive ceramic scaffolds with improved tissue/material interface pore architecture in thin-wall bone defect

Three-dimensional (3D) printing bioactive ceramics have demonstrated alternative approaches to bone tissue repair, but an optimized materials system for improving the recruitment of host osteogenic cells into the bone defect and enhancing targeted repair of the thin-wall craniomaxillofacial defects remains elusive. Herein we systematically evaluated the role of side-wall pore architecture in the direct-ink-writing bioceramic scaffolds on mechanical properties and osteogenic capacity in rabbit calvarial defects. The pure calcium silicate (CSi) and dilute Mg-doped CSi (CSi-Mg6) scaffolds with different layer thickness and macropore sizes were prepared by varying the layer deposition mode from single-layer printing (SLP) to double-layer printing (DLP) and then by undergoing one-, or two-step sintering. It was found that the dilute Mg doping and/or two-step sintering schedule was especially beneficial for improving the compressive strength (∼25-104 MPa) and flexural strength (∼6-18 MPa) of the Ca-silicate scaffolds. The histological analysis for the calvarial bone specimens in vivo revealed that the SLP scaffolds had a high osteoconduction at the early stage (4 weeks) but the DLP scaffolds displayed a higher osteogenic capacity for a long time stage (8-12 weeks). Although the DLP CSi scaffolds displayed somewhat higher osteogenic capacity at 8 and 12 weeks, the DLP CSi-Mg6 scaffolds with excellent fracture resistance also showed appreciable new bone tissue ingrowth. These findings demonstrate that the side-wall pore architecture in 3D printed bioceramic scaffolds is required to optimize for bone repair in calvarial bone defects, and especially the Mg doping wollastontie is promising for 3D printing thin-wall porous scaffolds for craniomaxillofacial bone defect treatment.

The outstanding mechanical response and bone regeneration capacity of robocast dilute magnesium-doped wollastonite scaffolds in critical size bone defects

The regeneration and repair of damaged load-bearing segmental bones require considerable mechanical strength for the artificial implants. The ideal biomaterials should also facilitate the production of porous implants with high bioactivity desirable for stimulating new bone growth. Here we developed a new mechanically strong, highly bioactive dilute magnesium-doped wollastonite (CaSiO3-Mg; CSi-Mg) porous scaffold by the robocasting technique. The sintered scaffolds had interconnected pores 350 µm in size and over 50% porosity with appreciable compressive strength (>110 MPa), 5-10 times higher than those of pure CSi and β-TCP porous ceramics. Extensive in vitro and in vivo investigations revealed that such Ca-silicate bioceramic scaffolds were particularly beneficial for osteogenic cell activity and osteogenic capacity in critical size femoral bone defects. The CSi-Mg porous constructs were accompanied by an accelerated new bone growth (6-18 weeks) and a mechanically outstanding elastoplastic response to finally match the strength (10-15 MPa) of the rabbit femur host bone after 18 weeks, and the material itself experienced mild resorption and apatite-like phase transformation. In contrast, the new bone regeneration in the β-TCP scaffolds was substantially retarded after 6-12 weeks of implantation, and exhibited a low level of mechanical strength (<10 MPa) similar to the pure CSi scaffolds. These results suggest a promising application of robocast CSi-Mg scaffolds in the clinic, especially for the load-bearing bone defects.

Hybrid calcium phosphate coatings with the addition of trace elements and polyaspartic acid by a low-thermal process

Research in the field of orthopedic implantology is currently focused on developing methodologies to potentiate osseointegration and to expedite the reestablishment of full functionality. We have developed a simple biomimetic approach for preparing trace elements-codoped calcium phosphate (teCaP) coatings on a titanium substrate. The reaction proceeded via low-thermal incubation in trace elements (TEs)-added simulated body fluid (teSBF) at 90 and 120 °C. The x-ray photoelectron spectroscopy, x-ray diffraction and energy-dispersive x-ray analyses demonstrated that the teCaP coating was the composite of hydroxyapatite and whitlockite, simultaneously doped with magnesium, strontium, zinc and silicon. The addition of polyaspartic acid and TEs into SBF significantly densified the coating. The incubation temperature is another important factor controlling the coating precipitation rate and bonding strength. An incubation temperature of 120 °C could accelerate the coating precipitation and improve the interface bonding strength. The in vitro cell culture investigation indicated that the teCaP coating supported the adhesion and spreading of ovariectomized rat mesenchymal stem cells (rMSCs) and particularly, promoted rMSCs proliferation compared to the CaP coating prepared in SBF. Collectively, from such a biomimetic route there potentially arises a general procedure to prepare a wide range of bioactive teCaP coatings of different composition for osteoporotic osteogenic cells activation response.

Octacalcium phosphate microscopic superstructure self-assembly and evolution by dual-mediating combination

The morphologies of biomimetic mineralized octacalcium phosphate (OCP) are extremely versatile. Numerous studies have addressed the gel phases, surfactants, polyelectrolytes and thin layers as convenient media to produce OCP nanostructures with various morphologies. However, hardly any studies have to date discussed the concept of controlling the structural evolution of these nanostructures by organic molecule mediation. This paper aims at opening the pathway to such OCP assemblies with levels of morphological expression and evolution from an aqueous solution consisting of highly diluted acidic macromolecule and amphiphilic small molecule as co-mediators. This approach differs in that the usual organic molecules are used to shape the single OCP morphology, and specifically establish an evolutionary relationship between the lamellar clusters and spherical aggregates. We present a possible model that gives qualitative description for the morphology of OCP grown in a variety of molar ratios between acidic macromolecule and small molecule surfactant. We believe that extension of the present approach to other biominerals and inorganic materials will prepare a large variety of highly flexible biomimetic nanostructures with elaborate superstructures across nanoscale to macroscopic dimensions.