Elucidating osseointegration in vivo in 3D printed scaffolds eliciting different foreign body responses.

Osseointegration between biomaterial and bone is critical for the clinical success of many orthopaedic and dental implants. However, the mechanisms of in vivo interfacial bonding formation and the role of immune cells in this process remain unclear. In this study, we investigated the bone-scaffold material interfaces in two different 3D printed porous scaffolds (polymer/hydroxyapatite and sintered hydroxyapatite) that elicited different levels of foreign body response (FBR). The polymer/hydroxyapatite composite scaffolds elicited more intensive FBR, which was evidenced by more FBR components, such as macrophages/foreign body giant cells and fibrous tissue, surrounding the material surface. Sintered hydroxyapatite scaffolds showed less intensive FBR compared to the composite scaffolds. The interfacial bonding appeared to form via new bone first forming within the pores of the scaffolds followed by growing towards strut surfaces. In contrast, it was previously thought that bone regeneration starts at biomaterial surfaces via osteogenic stem/progenitor cells first attaching to them. The material-bone interface of the less immunogenic hydroxyapatite scaffolds was heterogenous across all samples, evidenced by the coexistence of osseointegration and FBR components. The presence of FBR components appeared to inhibit osseointegration. Where FBR components were present there was no osseointegration. Our results offer new insight on the in vivo formation of bone-material interface, which highlights the importance of minimizing FBR to facilitate osseointegration for the development of better orthopaedic and dental biomaterials.

Characterisation of bone regeneration in 3D printed ductile PCL/PEG/hydroxyapatite scaffolds with high ceramic microparticle concentrations.

3D printed bioactive glass or bioceramic particle reinforced composite scaffolds for bone tissue engineering currently suffer from low particle concentration (<50 wt%) hence low osteoconductivity. Meanwhile, composites with very high inorganic particle concentrations are very brittle. Scaffolds combining high particle content and ductility are urgently required for bone tissue engineering. Herein, 3D printed PCL/hydroxyapatite (HA) scaffolds with high ceramic concentration (up to 90 wt%) are made ductile (>100% breaking strain) by adding poly(ethylene glycol) which is biocompatible and FDA approved. The scaffolds require no post-printing washing to remove hazardous components. More exposure of HA microparticles on strut surfaces is enabled by incorporating higher HA concentrations. Compared to scaffolds with 72 wt% HA, scaffolds with higher HA content (90 wt%) enhance matrix formation but not new bone volume after 12 weeks implantation in rat calvarial defects. Histological analyses demonstrate that bone regeneration within the 3D printed scaffolds is via intramembranous ossification and starts in the central region of pores. Fibrous tissue that resembles non-union tissue within bone fractures is formed within pores that do not have new bone. The amount of blood vessels is similar between scaffolds with mainly fibrous tissue and those with more bone tissue, suggesting vascularization is not a deciding factor for determining the type of tissues regenerated within the pores of 3D printed scaffolds. Multinucleated immune cells are commonly present in all scaffolds surrounding the struts, suggesting a role of managing inflammation in bone regeneration within 3D printed scaffolds.

Cryogenically printed flexible chitosan/bioglass scaffolds with stable and hierarchical porous structures for wound healing.

Wound healing is a dynamic and well-orchestrated process that can be promoted by creating an optimal environment with wound dressing. An ideal wound dressing material should possess a suitable matrix, structure and bioactive components, functioning synergistically to accelerate wound healing. Wound dressings that allow reproducibility and customizability are highly desirable in clinical practice. In this study, using chitosan (CS) as the matrix and bioglass (BG) as the biological component, a spatially designed dressing scaffold was fabricated from a home-made cryogenic printing system. The micro- and macro-structures of the scaffold were highly controllable and reproducible. The printed scaffold exhibited interconnected and hierarchical pore structures, as well as good flexibility and water absorption capacity, and these properties were not affected by the content of BG. Nevertheless, when the content of BGs exceeded 20% that of CS, the tension strength and elongation rate reduced, but in vitro antibacterial, cell proliferation and migration performance were enhanced. In vivo examinations revealed that the composite scaffold significantly promoted wound healing process, with the group having 30% bioglass showing better wound closure, neovascularization and collagen deposition than other groups. These results indicate that the 3D printed CS/BG composite scaffold is a promising dressing material that accelerates wound healing.

Magnesium-alloy rods reinforced bioglass bone cement composite scaffolds with cortical bone-matching mechanical properties and excellent osteoconductivity for load-bearing bone in vivo regeneration.

Various therapeutic platforms have been developed for repairing bone defects. However, scaffolds possess both cortical bone-matching mechanical properties and excellent osteoconductivity for load-bearing bone defects repair is still challenging in the clinic. In this study, inspired by the structure of the ferroconcrete, a high-strength bifunctional scaffold has been developed by combining surface-modified magnesium alloy as the internal load-bearing skeleton and bioglass-magnesium phosphate bone cement as the osteoconductive matrix. The scaffold combines the high mechanical strength and controllable biodegradability of surface-modified magnesium alloy with the excellent biocompatibility and osteoconductivity of bioglass-magnesium phosphate bone cement, thus providing support for load-bearing bone defects and subsequently bone regeneration. The scaffolds generate hydroxyapatite (HA) during the degrading in simulated body fluid (SBF), with the strength of the scaffold decreasing from 180 to 100 MPa in 6 weeks, which is still sufficient for load-bearing bone. Moreover, the scaffolds showed excellent osteoconductivity in vitro and in vivo. In a New Zealand White Rabbit radius defect model, the scaffolds degrade gradually and are replaced by highly matured new bone tissues, as assessed by image-based analyses (X-ray and Micro-CT) and histological analyses. The bone formation-related proteins such as BMP2, COL1a1 and OCN, all showed increased expression.

Customized Borosilicate Bioglass Scaffolds With Excellent Biodegradation and Osteogenesis for Mandible Reconstruction.

Graft reconstruction of the mandible is an important approach that aims at improving the appearance and functionality of defected mandibles. The traditional implant materials are generally bioinert, non-degradable, and that they lack favorable pore structures for cell proliferation, which limit their clinical application. In this study, we used boron-containing bioactive glass which was combined with a three-dimensional (3D) printing technology to construct an osteoinductive implant scaffold, according to the imaging instructions of CT scan on bone defects. Here, the boron-containing bioglass scaffold (B-BGs) was prepared through sol-gel processing and a 3D print technique. Different boron content of borosilicate bioglass was prepared by incorporating B2O3 (molar: 19.4 and 38.8%) into 58S bioglass to replace parts of SiO2. For fabricated mandible implants through three-dimensional 3D printing of B-BGs (size: 8 × 2 mm; pore size: 250 µm) modified with borosilicate bioglass powder and sodium alginate. Notably, the compressive strength of the B-BGs was about 3.8 Mpa, which supported mandibular activity. Subsequently, the excellent biocompatibility of B-BGs was confirmed using cytotoxicity in vitro studies. Finally, data from in vivo experiments demonstrated that the B-BGs could promote bone regeneration and they could almost get completely degraded within 4 weeks. Our results showed that the boron-containing bioglass could repair mandibular defects.

Research of Cu-Doped Hydroxyapatite Microbeads Fabricated by Pneumatic Extrusion Printing.

Copper is an indispensable micronutrient in human health, which has important effects on the promotion of angiogenesis and thus contributes to bone formation and antimicrobial activity. We used ion exchange and pneumatic printing methods to prepare hydroxyapatite (HA) microspheres with different copper content. The microspheres were characterized by scanning electron microscope (SEM), X-ray diffractometry (XRD) and X-Ray photoelectron spectroscopy (XPS). Considering the resistance of hydroxyapatite to biodegradation in vivo, the degradation rate of microspheres in modified simulated body fluids was studied. In addition, cell proliferation and antibacterial experiments were carried out to study the biological properties of microspheres. HA-1.5MCu microbeads treated by 1.5 mol/L CuSO4 curing solution have good performance on degradation, antibacterial properties and cell survival rate on day 7. The results showed that HA-1.5MCu microbeads may be used as a good repair material for bone defects.