Sanzhong Xu

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.

Results of operative treatment of avulsion fractures of the iliac crest apophysis in adolescents

BACKGROUND Avulsion fracture of the iliac crest apophysis is a rare condition that commonly occurs in adolescent athletes. Conservative treatment for this injury can produce excellent functional outcomes. However, the rehabilitation process requires a rather long immobilisation period. This study aimed to evaluate the use of cannulated screws for fixation of avulsion fractures of iliac crest apophysis. METHODS Ten patients with avulsion fractures of iliac crest apophysis were treated by open reduction and internal fixation using cannulated screws. RESULTS The mean age of patients was 14.6 years (range, 13-15 years). The mean intraoperative blood loss was 14.9 ml (range, 10-25 ml). The mean operative time was 40.3 min (range, 33-52 min). The mean follow-up period was 11.2 months (range, 6-20 months). At the 4-week follow-up, all patients returned to previously normal activity without pain and had no evidence of lower extremity muscle weakness. At the final follow-up, all patients resumed their athletic activity without any complications. CONCLUSION Open reduction and internal fixation for the treatment of avulsion fracture of iliac crest apophysis can be recommended for patients requiring rapid rehabilitation.

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.

3D printing of Mg-substituted wollastonite reinforcing diopside porous bioceramics with enhanced mechanical and biological performances

Mechanical strength and its long-term stability of bioceramic scaffolds is still a problem to treat the osteonecrosis of the femoral head. Considering the long-term stability of diopside (DIO) ceramic but poor mechanical strength, we developed the DIO-based porous bioceramic composites via dilute magnesium substituted wollastonite reinforcing and three-dimensional (3D) printing. The experimental results showed that the secondary phase (i.e. 10% magnesium substituting calcium silicate; CSM10) could readily improve the sintering property of the bioceramic composites (DIO/CSM10-x, x = 0–30) with increasing the CSM10 content from 0% to 30%, and the presence of the CSM10 also improved the biomimetic apatite mineralization ability in the pore struts of the scaffolds. Furthermore, the flexible strength (12.5–30 MPa) and compressive strength (14–37 MPa) of the 3D printed porous bioceramics remarkably increased with increasing CSM10 content, and the compressive strength of DIO/CSM10-30 showed a limited decay (from 37 MPa to 29 MPa) in the Tris buffer solution for a long time stage (8 weeks). These findings suggest that the new CSM10-reinforced diopside porous constructs possess excellent mechanical properties and can potentially be used to the clinic, especially for the treatment of osteonecrosis of the femoral head work as a bioceramic rod.

45S5 Bioglass analogue reinforced akermanite ceramic favorable for additive manufacturing mechanically strong scaffolds

Calcium–magnesium silicate bioceramics have attracted increased interest in the development of porous scaffolds for bone tissue engineering applications, mainly due to their excellent bioactivity and ability to bond to hard tissue. However, the shaping of these bioceramics into complex porous constructs is challenging, and, especially, conventional high temperature pressureless sintering is not always an effective method to improve their mechanical properties without further compromising their biologically relevant performances. Here we developed a low melting-point bioactive glass (BG)-assisted sintering approach to improve the mechanical properties of akermanite ceramics with and without intentionally manufacturing macroporous structures. The experimental results indicated that the 4 wt% B2O3-containing 45S5 BG analogue could readily reinforce akermanite ceramics at a 20–40 wt% content, and material extrusion 3D-printing followed by a pressureless sintering process could be employed to fabricate high-strength porous scaffolds with compressive strength (∼36 MPa) ten times higher than those of pure akermanite porous ceramics. Moreover, the composite porous ceramics showed slower biodegradation in Tris buffer in vitro and this did not heavily affect the strength of their porous formulation over a long time period (6 weeks). It is proposed that 3D printing followed by an NCS-B-assisted sintering process represents an effective alternative for developing high strength bioceramic scaffolds potentially for the repair of load-bearing segmental bone defects.

Combination of methylprednisolone and rosiglitazone promotes recovery of neurological function after spinal cord injury

Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-γ in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally injected with methylprednisolone (30 mg/kg) and rosiglitazone (2 mg/kg) at 1 hour after injury, and methylprednisolone (15 mg/kg) at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better promoted recovery of neurological function after injury.

Preparation and in vitro evaluation of strontium-doped calcium silicate/gypsum bioactive bone cement

The combination of two or more bioactive components with different biodegradability could cooperatively improve the physicochemical and biological performances of the biomaterials. Here we explore the use of α-calcium sulfate hemihydrate (α-CSH) and calcium silicate with and without strontium doping (Sr-CSi, CSi) to fabricate new bioactive cements with appropriate biodegradability as bone implants. The cements were fabricated by adding different amounts (0-35 wt%) of Sr-CSi (or CSi) into the α-CSH-based pastes at a liquid-to-solid ratio of 0.4. The addition of Sr-CSi into α-CSH cements not only led to a pH rise in the immersion medium, but also changed the surface reactivity of cements, making them more bioactive and therefore promoting apatite mineralization in simulated body fluid (SBF). The impact of additives on long-term in vitro degradation was evaluated by soaking the cements in Tris buffer, SBF, and α-minimal essential medium (α-MEM) for a period of five weeks. An addition of 20% Sr-CSi to α-CSH cement retarded the weight loss of the samples to 36% (in Tris buffer), 43% (in SBF) and 54% (in α-MEM) as compared with the pure α-CSH cement. However, the addition of CSi resulted in a slightly faster degradation in comparison with Sr-CSi in these media. Finally, the in vitro cell-ion dissolution products interaction study using human fetal osteoblast cells demonstrated that the addition of Sr-CSi improved cell viability and proliferation. These results indicate that tailorable bioactivity and biodegradation behavior can be achieved in gypsum cement by adding Sr-CSi, and such biocements will be of benefit for enhancing bone defect repair.

Rational design and fabrication of a β-dicalcium silicate-based multifunctional cement with potential for root canal filling treatment

The integration of physicochemical and biological performances in root canal treatment represents a challenge for long-time antileakage, antibacterial, and even inducing periradicular cementum/bone tissue regeneration. The objective of this work is to develop a β-Ca2SiO3 (β-C2Si)-based cement as a new root canal filler with good antibacterial ability, sealability and bioactivity. β-C2Si powders with controllable free CaO content were prepared by regulating the calcium/silicate molar ratio in reaction medium. It was demonstrated that a composite paste with 10-30 wt% α-gypsum at a liquid-to-powder ratio of 0.6 ml g-1 remained injectable for 12 min and provided a significant pH rise during setting. Notably, the hydraulic cements with high free CaO contents exhibited bactericidal or bacteriostatic properties against three bacterial strains, Streptococci mutans, Actinomyces naeslundii, and Actinomyces viscosus, which were demonstrated by the agar diffusion method. Also, the injected paste in root canal ex vivo showed extremely low microleakage of Rhodamine B but a good apatite-mineralization response. Therefore, these intrinsic antibacterial activity, bioactivity, injectability and tight adaption to root canal sealability make β-C2Si/α-gypsum composites preferential candidates for application in endodontics, such as root-end filling, pulp capping therapy, microleakage prevention, as well as for inducing hard tissue regeneration.

Design and evaluation of multifunctional antibacterial ion-doped β-dicalcium silicate cements favorable for root canal sealing

A root canal sealer plays some important roles in accomplishing various functions including antibacteria and anti-microleakage. Meanwhile, such a sealer is also expected to readily induce apatite mineralization in damaged periapical tissues and reconstruct the surrounding alveolar bone. Taking the potent antibacterial ability of some biologically essential trace elements into account, we explore the effects of Zn or Cu doping in β-dicalcium silicate (β-C2Si) on the physicochemical modification and biological functions of its self-curing cement and compare with the β-C2Si cement free of foreign ion doping. An interesting aspect of the Zn or Cu doping in β-C2Si was the prolongation of setting time and the decrease of mechanical strength, but retardation in the degradation and improvement of anti-microleakage. Furthermore, the β-C2Si doped with 10% Cu exhibited more excellent antibacterial properties against P. gingivalis and E. faecalis. Additionally, there was similar apatite formation ability and cell growth on the β-C2Si cements with and without Zn-/Cu-doping within the initial 1–5 d. Totally, it is demonstrated that the physicochemical and biological performances are favorably altered with Zn or Cu doping in β-C2Si with a consequent effect on setting time, chemical stability (ion release, degradation), anti-microleakage, and antibacterial activity. Therefore, it is indicated that the Zn or Cu-doped β-C2Si is promising as a multifunctional root canal sealer.