A Novel Bone Substitute with High Bioactivity, Strength, and Porosity for Repairing Large and Load-Bearing Bone Defects.

Achieving adequate healing in large or load-bearing bone defects is highly challenging even with surgical intervention. The clinical standard of repairing bone defects using autografts or allografts has many drawbacks. A bioactive ceramic scaffold, strontium-hardystonite-gahnite or "Sr-HT-Gahnite" (a multi-component, calcium silicate-based ceramic) is developed, which when 3D-printed combines high strength with outstanding bone regeneration ability.

Triple-Bioinspired Burying/Crosslinking Interfacial Coassembly Strategy for Layer-by-Layer Construction of Robust Functional Bioceramic Self-Coatings for Osteointegration Applications.

Coating bioceramics of inherent bioactivity onto biometallic implants is a straightforward yet promising solution to address poor osteointegration of the latter. One step further, it would be a nontrivial accomplishment to develop a mild, cheap, and universal route to firmly stabilizing, in principle, any ceramics onto any implant substrate, while imparting expectedly versatile biofunctional performances. Herein, we describe a triple-bioinspired burying/cross-linking interfacial coassembly strategy for enabling such ceramic coatings, which ingeniously fuses bioinspiration from sea rocks (burying assisted particle immobilization), marine mussels (universal adhesion and versatile chemical reactivity), and reef-building oysters (cross-linking rendered cohesion).

Effects of Sr-HT-Gahnite on osteogenesis and angiogenesis by adipose derived stem cells for critical-sized calvarial defect repair.

Tissue engineering strategies to construct vascularized bone grafts are now attracting much attention. Strontium-hardystonite-Gahnite (Sr-HT-Gahnite) is a strong, highly porous, and biocompatible calcium silicate based bio-ceramic that contains strontium and zinc ions. Adipose derived stem cells (ASCs) have been demonstrated to have the ability in promoting osteogenesis and angiogenesis.

In vitro response of macrophages to ceramic scaffolds used for bone regeneration.

Macrophages, the primary cells of the inflammatory response, are major regulators of healing, and mediate both bone fracture healing and the inflammatory response to implanted biomaterials. However, their phenotypic contributions to biomaterial-mediated bone repair are incompletely understood. Therefore, we used gene expression and protein secretion analysis to investigate the interactions in vitro between primary human monocyte-derived macrophages and ceramic scaffolds that have been shown to have varying degrees of success in promoting bone regeneration in vivo Specifically, baghdadite (Ca3ZrSi2O9) and strontium-hardystonite-gahnite (Sr-Ca2ZnSi2O7-ZnAl2O4) scaffolds were chosen as two materials that enhanced bone regeneration in vivo in large defects under load compared with clinically used tricalcium phosphate-hydroxyapatite (TCP-HA).

Fracture behaviors of ceramic tissue scaffolds for load bearing applications.

Healing large bone defects, especially in weight-bearing locations, remains a challenge using available synthetic ceramic scaffolds. Manufactured as a scaffold using 3D printing technology, Sr-HT-Gahnite at high porosity (66%) had demonstrated significantly improved compressive strength (53 ± 9 MPa) and toughness. Nevertheless, the main concern of ceramic scaffolds in general remains to be their inherent brittleness and low fracture strength in load bearing applications.

A bioceramic with enhanced osteogenic properties to regulate the function of osteoblastic and osteocalastic cells for bone tissue regeneration.

Bioceramics for regenerative medicine applications should have the ability to promote adhesion, proliferation and differentiation of osteoblast and osteoclast cells. Osteogenic properties of the material are essential for rapid bone regeneration and new bone formation. The aim of this study was to develop a silicate-based ceramic, gehlenite (GLN, Ca2Al2SiO7), and characterise its physiochemical, biocompatibility and osteogenic properties.

Efficacy of novel synthetic bone substitutes in the reconstruction of large segmental bone defects in sheep tibiae.

The treatment of large bone defects, particularly those with segmental bone loss, remains a significant clinical challenge as current approaches involving surgery or bone grafting often do not yield satisfactory long-term outcomes. This study reports the evaluation of novel ceramic scaffolds applied as bone graft substitutes in a clinically relevant in vivo model. Baghdadite scaffolds, unmodified or modified with a polycaprolactone coating containing bioactive glass nanoparticles, were implanted into critical-sized segmental bone defects in sheep tibiae for 26 weeks.

Design and Fabrication of 3D printed Scaffolds with a Mechanical Strength Comparable to Cortical Bone to Repair Large Bone Defects.

A challenge in regenerating large bone defects under load is to create scaffolds with large and interconnected pores while providing a compressive strength comparable to cortical bone (100-150 MPa). Here we design a novel hexagonal architecture for a glass-ceramic scaffold to fabricate an anisotropic, highly porous three dimensional scaffolds with a compressive strength of 110 MPa. Scaffolds with hexagonal design demonstrated a high fatigue resistance (1,000,000 cycles at 1-10 MPa compressive cyclic load), failure reliability and flexural strength (30 MPa) compared with those for conventional architecture.

Silk coating on a bioactive ceramic scaffold for bone regeneration: effective enhancement of mechanical and in vitro osteogenic properties towards load-bearing applications.

Bioactive ceramic scaffolds represent competitive choices for clinical bone reconstruction, but their widespread use is restricted by inherent brittleness and weak mechanical performance under load. This study reports the development of strong and tough bioactive scaffolds suitable for use in load-bearing bone reconstruction. A strong and bioactive ceramic scaffold (strontium-hardystonite-gahnite) is combined with single and multiple coating layers of silk fibroin to enhance its toughness, producing composite scaffolds which match the mechanical properties of cancellous bone and show enhanced capacity to promote in vitro osteogenesis.

A biphasic scaffold based on silk and bioactive ceramic with stratified properties for osteochondral tissue regeneration.

Significant clinical challenges encountered in the effective long-term treatment of osteochondral defects have inspired advancements in scaffold-based tissue engineering techniques to aid repair and regeneration. This study reports the development of a biphasic scaffold produced via a rational combination of silk fibroin and bioactive ceramic with stratified properties to satisfy the complex and diverse regenerative requirements of osteochondral tissue. Structural examination showed that the biphasic scaffold contained two phases with different pore morphologies to match the cartilage and bone segments of osteochondral tissue, which were joined at a continuous interface.

Zirconium ions up-regulate the BMP/SMAD signaling pathway and promote the proliferation and differentiation of human osteoblasts.

Zirconium (Zr) is an element commonly used in dental and orthopedic implants either as zirconia (ZrO2) or in metal alloys. It can also be incorporated into calcium silicate-based ceramics. However, the effects of in vitro culture of human osteoblasts (HOBs) with soluble ionic forms of Zr have not been determined.

Micro-poro-elasticity of baghdadite-based bone tissue engineering scaffolds: a unifying approach based on ultrasonics, nanoindentation, and homogenization theory.

Microstructure-elasticity relations for bone tissue engineering scaffolds are key to rational biomaterial design. As a contribution thereto, we here report comprehensive length measuring, weighing, and ultrasonic tests at 0.1MHz frequency, on porous baghdadite (Ca3ZrSi2O9) scaffolds.

Injectable radiopaque and bioactive polycaprolactone-ceramic composites for orthopedic augmentation.

The aim of this study was to develop and characterize an injectable bone void filler by incorporating baghdadite (Ca3 ZrSi2 O9 ) particles (average size of 1.7 µm) into polycaprolactone (PCL). A series of PCL composites containing different volume percentages of baghdadite [1 (PCL-1%Bag), 5 (PCL-5%Bag), 10 (PCL-10%Bag), 20 (PCL-20%Bag), and 30 (PCL-30%Bag)] were prepared, and their injectability, setting time, mechanical properties, radiopacity, degradation, and cytocompatibility were investigated.

Nanomaterials: the next step in injectable bone cements.

Injectable bone cements (IBCs) are biocompatible materials that can be used as bone defect fillers in maxillofacial surgeries and in orthopedic fracture treatment in order to augment weakened bone due to osteoporosis. Current clinically available IBCs, such as polymethylmethacrylate and calcium phosphate cement, have certain advantages; however, they possess several drawbacks that prevent them from gaining universal acceptance. New gel-based injectable materials have also been developed, but these are too mechanically weak for load-bearing applications.

Synergistic effect of nanomaterials and BMP-2 signalling in inducing osteogenic differentiation of adipose tissue-derived mesenchymal stem cells.

The lack of complete understanding in the signalling pathways that control the osteogenic differentiation of mesenchymal stem cells hinders their clinical application in the reconstruction of large bone defects and non-union bone fractures. The aim of this study is to gain insight into the interactions of bone morphogenetic protein-2 (BMP-2) and bone biomimetic scaffolds in directing osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ASCs) and the underlying signalling pathways involved. We demonstrated that bioactive glass nanoparticles (nBG) incorporated polycaprolactone (PCL) coating on hydroxyapatite/β-tricalcium phosphate (HA/TCP) scaffold exerted a synergistic effect with 3days of BMP-2 treatment in promoting osteogenic gene expression levels (Runx-2, collagen I, osteopontin and bone sialoprotein) and alkaline phosphatase activity in ASCs.

Fabrication of a novel triphasic and bioactive ceramic and evaluation of its in vitro and in vivo cytocompatibility and osteogenesis.

We report, for the first time, the synthesis of a novel triphasic and crystalline bioactive ceramic (MSM-10) with the ability to simultaneously release three types of bioactive ions (strontium (Sr), silicon (Si) and magnesium (Mg)) to the surrounding microenvironment. An MSM-10 powder with a nominal composition (wt%) of 54 MgSiO, 36 SiSr and 10 MgO was prepared by the sol-gel method and fabricated as porous scaffolds using the foam replication method. The effects of the different amounts of the phases in the ceramics on the mechanical and physical properties of the scaffolds as well as their in vitro and in vivo behaviors were comprehensively investigated.

Mimicking bone microenvironment for directing adipose tissue-derived mesenchymal stem cells into osteogenic differentiation.

Adipose tissue-derived mesenchymal stem cells (ASCs) have become an increasingly interested cell source for the scientists in the fields of stem cell biology and regenerative medicine. ASCs have already been used in a number of clinical trials, and some successful outcomes have been reported in bone tissue regeneration. Here we describe the protocols which mimic the factors in bone healing microenvironment, including inflammation burst, osteoblasts, and bone biomimetic scaffolds to direct ASCs into osteogenic differentiation.

Multiple silk coatings on biphasic calcium phosphate scaffolds: effect on physical and mechanical properties and in vitro osteogenic response of human mesenchymal stem cells.

Ceramic scaffolds such as biphasic calcium phosphate (BCP) have been widely studied and used for bone regeneration, but their brittleness and low mechanical strength are major drawbacks. We report the first systematic study on the effect of silk coating in improving the mechanical and biological properties of BCP scaffolds, including (1) optimization of the silk coating process by investigating multiple coatings, and (2) in vitro evaluation of the osteogenic response of human mesenchymal stem cells (hMSCs) on the coated scaffolds. Our results show that multiple silk coatings on BCP ceramic scaffolds can achieve a significant coating effect to approach the mechanical properties of native bone tissue and positively influence osteogenesis by hMSCs over an extended period.

Bone biomimetic microenvironment induces osteogenic differentiation of adipose tissue-derived mesenchymal stem cells.

Unlabelled: A critical strategy for tissue engineering is to provide the signals necessary for tissue regeneration by mimicking the tissue microenvironment. In this study, we mimicked (1) the bone chemical and the physical microenvironment by fabricating a three-dimensional nanocomposite scaffold composed of biphasic calcium phosphates (BCP) coated with a nanocomposite layer of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) (BCP/PCL-nHA)), and (2) the bone's biological microenvironment by co-culturing with primary human osteoblasts (HOBs), and then investigated their effects on osteogenic differentiation of adipose tissue-derived stem cells (ASCs). In comparison with the ASCs cultured alone on BCP scaffolds that were coated only with PCL, early osteogenic differentiation of ASCs was induced by either seeding ASCs on BCP/PCL-nHA scaffolds or by co-culturing with HOBs; the combination of BCP/PCL-nHA scaffold and HOBs resulted in the synergistic enhancement of osteogenic gene expression.

Osteoblasts on rod shaped hydroxyapatite nanoparticles incorporated PCL film provide an optimal osteogenic niche for stem cell differentiation.

After the clinical insertion of a bone biomaterial, the surrounding osteoblasts would migrate and attach to the implant surface and foster a microenvironment that largely determines the differentiation fate of the comigrated mesenchymal stem cells. Whether the fostered microenvironment is suitable for osteogenic differentiation of mesenchymal stem cells is critical for the subsequent osseointegration. In this study, we determined (1) how the spherical or rod-shaped hydroxyapatite nanoparticles (nHA) incorporated poly(ɛ-caprolactone) (PCL) films (PCL-spherical nHA, PCL-rod nHA) interact with primary human osteoblasts (HOBs); (2) how the microenvironment rendered by their interaction affects osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ASCs).

The influence hydroxyapatite nanoparticle shape and size on the properties of biphasic calcium phosphate scaffolds coated with hydroxyapatite-PCL composites.

We developed a composite biphasic calcium phosphate (BCP) scaffold by coating a nanocomposite layer, consisting of hydroxyapatite (HA) nanoparticles and polycaprolactone (PCL), over the surface of BCP. The effects of HA particle size and shape in the coating layer on the mechanical and biological properties of the BCP scaffold were examined. Micro-computerized tomography studies showed that the prepared scaffolds were highly porous (approximately 91%) with large pore size (400-700 microm) and an interconnected porous network of approximately 100%.