Role of Biomaterials and Controlled Architecture on Tendon/Ligament Repair and Regeneration.

Engineering synthetic scaffolds to repair and regenerate ruptured native tendon and ligament (T/L) tissues is a significant engineering challenge due to the need to satisfy both the unique biological and biomechanical properties of these tissues. Long-term clinical outcomes of synthetic scaffolds relying solely on high uniaxial tensile strength are poor with high rates of implant rupture and synovitis. Ideal biomaterials for T/L repair and regeneration need to possess the appropriate biological and biomechanical properties necessary for the successful repair and regeneration of ruptured tendon and ligament tissues.

Plasma-sprayed CaTiSiO5 ceramic coating on Ti-6Al-4V with excellent bonding strength, stability and cellular bioactivity.

Novel Ca-Si-Ti-based sphene (CaTiSiO5) ceramics possess excellent chemical stability and cytocompatibility. The aim of this study was to prepare sphene coating on titanium alloy (Ti-6Al-4V) for orthopaedic applications using the plasma spray method. The phase composition, surface and interface microstructure, coating thickness, surface roughness and bonding strength of the plasma-sprayed sphene coating were analysed using X-ray diffraction, scanning electron microscopy, atomic force microscopy and the standard mechanical testing of the American Society for Testing and Materials, respectively. The results indicated that sphene coating was obtained with a uniform and dense microstructure at the interface of the Ti-6Al-4V surface and the thickness and surface roughness of the coating were approximately 150 and 10 microm, respectively. Plasma-sprayed sphene coating on Ti-6Al-4V possessed a significantly improved bonding strength and chemical stability compared with plasma-sprayed hydroxyapatite (HAp) coating. Plasma-sprayed sphene coating supported human osteoblast-like cell (HOB) attachment and significantly enhanced HOB proliferation and differentiation compared with plasma-sprayed HAp coating and uncoated Ti-6Al-4V. Taken together, plasma-sprayed sphene coating on Ti-6Al-4V possessed excellent bonding strength, chemical stability and cellular bioactivity, indicating its potential application for orthopaedic implants.

Novel injectable strontium-hardystonite phosphate cement for cancellous bone filling applications.

Injectable bone cement (IBC) such as those based on methacrylates and hydraulic calcium phosphate and calcium sulfate-based cements have been used extensively for filling bone defects with acceptable clinical outcomes. There is a need however for novel IBC materials that can address some of the inherent limitations of currently available formulations to widen the clinical application of IBC. In this study, we characterized a novel hydraulic IBC formulation consisting of bioactive strontium-doped hardystonite (Sr-HT) ceramic microparticles and sodium dihydrogen phosphate, herein named Sr-HT phosphate cement (SPC). The resultant cement is comprised of two distinct amorphous phases with embedded partially reacted crystalline reactants. The novel SPC formulation possesses a unique combination of physicochemical properties suitable for use as an IBC, and demonstrates in vitro cytocompatibility when seeded with primary human osteoblasts. In vivo injection of SPC into rabbit sinus defects show minor new bone formation at the SPC periphery, similar to those exhibited in sinus defects filled with a clinically available calcium phosphate cement. The current SPC formulation presented in this paper shows promise as a clinically applicable IBC which can be further enhanced with additives.

Biological response of human bone cells to zinc-modified Ca-Si-based ceramics.

Calcium silicate (CaSiO(3)) ceramics have received considerable attention in recent years due to their excellent bioactivity and degradability. However, their poor chemical stability limits their biological applications. Hardystonite (Ca(2)ZnSi(2)O(7)) ceramics are Ca-Si-based materials developed by incorporating zinc into the Ca-Si system to improve their chemical stability. However, the biological responses of Ca(2)ZnSi(2)O(7) to bone cells are unknown. The objective of this study is to investigate and compare the in vitro responses of human osteoblast-like cells (HOBs) and osteoclasts when cultured on Ca(2)ZnSi(2)O(7) and CaSiO(3) ceramic disks. The ability of Ca(2)ZnSi(2)O(7) ceramics to support HOB attachment, cytoskeleton organization, proliferation and differentiation was assessed by scanning electron microscopy, confocal microscopy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, alkaline phosphatase activity and quantitative real-time polymerase chain reaction. Our results show that Ca(2)ZnSi(2)O(7) supported HOB attachment with a well-organized cytoskeleton structure, and significantly increased cellular proliferation and differentiation compared to CaSiO(3). In addition, Ca(2)ZnSi(2)O(7) showed increased expression levels of osteoblast-related mRNAs (alkaline phosphatase, collagen type I, osteocalcin, receptor activator of NF(kappa)B ligand and osteoprotegerin) compared to CaSiO(3). Ca(2)ZnSi(2)O(7) ceramic supported the formation of mature and functional osteoclasts and formed resorption imprints. On CaSiO(3) ceramics, the cells failed to differentiate from the monocytes into osteoclasts. Taken together, these results indicate that Hardystonite ceramics are conducive to both types of bone cells, osteoblast-like cells and osteoclasts, suggesting their potential use for skeletal tissue regeneration and as coatings onto currently available orthopedic and dental implants.

Improvement of mechanical and biological properties of porous CaSiO3 scaffolds by poly(D,L-lactic acid) modification.

Porous calcium silicates (CaSiO3, WT) are regarded as a potential bioactive material for bone tissue engineering. However, their insufficient mechanical strength and high dissolution (degradation) limit their biological applications. The aim of this study is to surface modify WT scaffolds with poly(d,l-lactic acid) (PDLLA) to improve their mechanical and biological properties. The phase composition, microstructure, porosity and interconnectivity of WT and PDLLA-modified WT (WTPL) scaffolds were analyzed by X-ray diffraction, scanning electron microscopy and micro-computerized tomography. The WTPL scaffolds maintained a more uniform and continuous inner network, compared to that of the WT scaffolds, while maintaining the pore size, porosity and interconnectivity of the original materials. The compressive strength, compressive modulus and percentage strain of the WT and WTPL scaffolds were assessed in air and phosphate-buffered saline. PDLLA modification significantly improved the compressive strength and decreased the brittleness of the WT scaffolds. The weight loss and apatite-forming ability of the two scaffolds were evaluated by soaking them in simulated body fluid (SBF) for 1, 3, 7, 14 and 28days. PDLLA modification decreased the dissolution of the WT scaffolds while maintaining their apatite-forming ability in SBF. In addition, PDLLA modification improved the spreading and viability of human bone-derived cells. Our results indicate that PDLLA-modified CaSiO3 scaffolds possess improved mechanical and biological properties, suggesting their potential application for bone tissue regeneration.

Novel sphene coatings on Ti-6Al-4V for orthopedic implants using sol-gel method.

Hydroxyapatite (HAp) is commonly used to coat titanium alloys (Ti-6Al-4V) for orthopedic implants. However, their poor adhesion strength and insufficient long-term stability limit their application. Novel sphene (CaTiSiO5) ceramics possess excellent chemical stability and cytocompatibility. The aim of this study is to use the novel sphene ceramics as coatings for Ti-6Al-4V. The sol-gel method was used to produce the coatings and the thermal properties, phase composition, microstructure, thickness, surface roughness and adhesion strength of sphene coatings were analyzed by differential thermal analysis-thermal gravity (DTA-TG), X-ray diffraction (XRD), scanning electron microscopy (SEM), atom force microscopy (AFM) and scratch test, respectively. DTA analysis confirmed that the temperature of the sphene phase formation is 875 degrees C and XRD analysis indicated pure sphene coatings were obtained. A uniform structure of the sphene coating was found across the Ti-6Al-4V surface, with a thickness and surface roughness of the coating of about 0.5-1 microm and 0.38 microm, respectively. Sphene-coated Ti-6Al-4V possessed a significantly improved adhesion strength compared to that for HAp coating and their chemical stability was evaluated by testing the profile element distribution and the dissolution kinetics of calcium (Ca) ions after soaking the sphene-coated Ti-6Al-4V in Tris-HCl solution. Sphene coatings had a significantly improved chemical stability compared to the HAp coatings. A layer of apatite formed on the sphene-coated Ti-6Al-4V after they were soaked in simulated body fluids (SBF). Our results indicate that sol-gel coating of novel sphene onto Ti-6Al-4V possessed improved adhesion strength and chemical stability, compared to HAp-coated Ti-6Al-4V prepared under the same conditions, suggesting their potential application as coatings for orthopedic implants.

The effect of strontium incorporation into CaSiO3 ceramics on their physical and biological properties.

CaSiO3 ceramics have been regarded as a potential bioactive material for bone regeneration. Strontium (Sr) as a trace element in human body has been found to have beneficial effects on bone formation. The aim of this study was to incorporate Sr into CaSiO3 bioactive ceramics and to investigate their effect(s) on phase transition, sintering property, apatite-formation ability, ionic dissolution, and human bone-derived cells (HBDC) proliferation. Sr containing CaSiO3 (Sr-CaSiO3) ceramics at various concentrations (0-10% Sr) were prepared. The incorporation of Sr into CaSiO3 promoted the phase transition from beta to alpha-CaSiO3 and enhanced ceramic densification but did not alter the mechanism and ability of apatite formation in SBF. The ionic dissolution rate of the Sr-CaSiO3 decreased compared to the CaSiO3. The addition of Sr decreased pH value in SBF. The effect of Sr-CaSiO3 extracts, carried out according to the International Standard Organization, on HBDC proliferation was evaluated. At high extract concentration (100 and 200 mg/mL), CaSiO3 was found to stimulate HBDC proliferation, however, the incorporation of Sr into CaSiO3 stimulated HBDC proliferation even at low extract concentration (ranging from 12.5, 25 to 50 mg/mL). Our results indicate that Sr-CaSiO3 ceramics improved the physical and biological properties of the pure CaSiO3 ceramics.

Promoting Cell Survival and Proliferation in Degradable Poly(vinyl alcohol)-Tyramine Hydrogels.

A photopolymerizable-tyraminated poly(vinyl alcohol) (PVA-Tyr) system that has the ability to covalently bind proteins in their native state was evaluated as a platform for cell encapsulation. However, a key hurdle to this system is the radicals generated during the cross-linking that can cause oxidative stress to the cells. This research hypothesized that incorporation of anti-oxidative proteins (sericin and gelatin) into PVA-Tyr gels would mitigate any toxicity caused by the radicals. The results showed that although incorporation of 1 wt% sericin promoted survival of the fibroblasts, both sericin and gelatin acted synergistically to facilitate long-term 3D cell function. The encapsulated cells formed clusters with deposition of laminin and collagen, as well as remaining metabolically active after 21 d.

Porous diopside (CaMgSi(2)O(6)) scaffold: A promising bioactive material for bone tissue engineering.

Diopside (CaMgSi(2)O(6)) powders and dense ceramics have been shown to be bioactive biomaterials for bone repair. The aim of this study is to prepare bioactive diopside scaffolds and examine their physicochemical and biological properties. X-ray diffraction, scanning electron microscopy (SEM), micro-computerized tomography and energy-dispersive spectrometry were used to analyse the composition, microstructure, pore size and interconnectivity of the diopside scaffolds. The mechanical strength and stability as well as the degradation of the scaffolds were investigated by testing the compressive strength, modulus and silicon ions released, respectively. Results showed that highly porous diopside scaffolds with varying porosity and high interconnectivity of 97% were successfully prepared with improved compressive strength and mechanical stability, compared to the bioglass and CaSiO(3) scaffolds. The bioactivity of the diopside scaffolds was assessed using apatite-forming ability in simulated body fluids (SBF) and by their support for human osteoblastic-like cell (HOB) attachment, proliferation and differentiation using SEM, and MTS and alkaline phosphatase activity assays, respectively. Results showed that diopside scaffolds possessed apatite-forming ability in SBF and supported HOB attachment proliferation and differentiation. Bioactive diopside scaffolds were prepared with excellent pore/structure art, and improved mechanical strength and mechanical stability, suggesting their possible applications for bone tissue engineering regeneration.

Orthopedic coating materials: considerations and applications.

The host response to titanium and its alloys is not always favorable, as a fibrous layer may form at the skeletal tissue-device interface, causing aseptic loosening. Therefore, a great deal of current orthopedic research is focused on developing implants with improved osseointegration properties in order to increase their clinical success. Promising new studies have been reported regarding coating the currently available implants with various coating materials and techniques so as to improve the long-term stability of implants. This article will discuss various coating materials developed, their advantages and disadvantages as coating materials and their biological performance.

Sphene ceramics for orthopedic coating applications: an in vitro and in vivo study.

The host response to titanium alloy (Ti-6Al-4V) is not always favorable as a fibrous layer may form at the skeletal tissue-device interface, causing aseptic loosening. Recently, sphene (CaTiSiO(5)) ceramics were developed by incorporating Ti in the Ca-Si system, and found to exhibit improved chemical stability. The aim of this study is to evaluate the in vitro response of human osteoblast-like cells, human osteoclasts and human microvascular endothelial cells to sphene ceramics and determine whether coating Ti-6Al-4V implants with sphene enhances anchorage to surrounding bone. The study showed that sphene ceramics support human osteoblast-like cell attachment with organized cytoskeleton structure and express increased mRNA levels of osteoblast-related genes. Sphene ceramics were able to induce the differentiation of monocytes to form functional osteoclasts with the characteristic features of f-actin and alpha(v)beta(3) integrin, and express osteoclast-related genes. Human endothelial cells were also able to attach and express the endothelial cell markers ZO-1 and VE-Cadherin when cultured on sphene ceramics. Histological staining, enzyme histochemistry and immunolabelling were used for identification of mineralized bone and bone remodelling around the coated implants. Ti-6Al-4V implants coated with sphene showed new bone formation and filled the gap between the implants and existing bone in a manner comparable to that of the hydroxyapatite coatings used as control. The new bone was in direct contact with the implants, whereas fibrous tissue formed between the bone and implant with uncoated Ti-6Al-4V. The in vivo assessment of sphene-coated implants supports our in vitro observation and suggests that they have the ability to recruit osteogenic cells, and thus support bone formation around the implants and enhance osseointegration.

The effect of mesoporous bioactive glass on the physiochemical, biological and drug-release properties of poly(DL-lactide-co-glycolide) films.

Poly(lactide-co-glycolide) (PLGA) has been widely used for bone tissue regeneration. However, it lacks hydrophilicity, bioactivity and sufficient mechanical strength and its acidic degradation by-products can lead to pH decrease in the vicinity of the implants. Mesoporous bioactive glass (MBG) with highly ordered structure (pore size 2-50nm) possesses higher bioactivity than non-mesoporous bioactive glass (BG). The aim of this study is to investigate the effect of MBG on the mechanical strength, in vitro degradation, bioactivity, cellular response and drug release of PLGA films and optimize their physicochemical, biological and drug-delivery properties for bone tissue engineering application. The surface and inner microstructure, mechanical strength and surface hydrophilicity of MBG/PLGA and BG/PLGA films were tested. Results indicated that MBG or BG was uniformly dispersed in the PLGA films. The incorporation of MBG into PLGA films significantly improved their tensile strength, modulus and surface hydrophilicity. MBG/PLGA resulted in an enhanced mechanical strength, in vitro degradation (water absorbance, weight loss and ions release), apatite-formation ability and pH stability in simulated body fluids (SBF), compared to BG/PLGA. MBG/PLGA and BG/PLGA films enhanced human osteoblastic-like cells (HOBs) attachment, spreading and proliferation compared to PLGA. HOBs differentiation was significantly upregulated when cells were cultured on 30 MBG/PLGA for 14 days, compared to 30 BG/PLGA. MBG/PLGA enhanced the accumulative release of dexamethazone (DEX) at early stages (0-200h) compared to BG/PLGA, however, after 200h, DEX-release rates for MBG/PLGA was slower than that of BG/PLGA. The contents of MBG in PLGA films can control the amount of DEX released. Taken together, MBG/PLGA films possessed excellent physicochemical, biological and drug-release properties, indicating their potential application for bone tissue engineering by designing 3D scaffolds according to their corresponding compositions.

Incorporation of titanium into calcium silicate improved their chemical stability and biological properties.

Calcium silicate (CaSiO(3)) is regarded as a potential bioactive material. However, its poor chemical stability and cytocompatibility limits its biological applications. The aim of this study is to incorporate Titanium (Ti) into CaSiO(3) to produce a ceramic with improved chemical stability and biological properties. Sphene (CaTiSiO(5)) ceramics were prepared by sintering sol-gel-derived CaTiSiO(5) powder compacts and their chemical stability was assessed by measuring the ions released and weight loss after soaking CaTiSiO(5) in simulating body fluid for 1, 3, 7, and 14 days. Results indicated that CaTiSiO(5) has a significantly improved chemical stability, compared with CaSiO(3). The ability of CaTiSiO(5) ceramics to support human bone-derived cells (HBDC) attachment, proliferation, and differentiation was assessed using scanning electron microscopy, MTS, and alkaline phosphatase activity assays, respectively. CaTiSiO(5) ceramics supported HBDC attachment and significantly enhanced their proliferation and differentiation, compared with CaSiO(3) ceramics. Taken together, this study demonstrates that the newly developed CaTiSiO(5) ceramics possess excellent chemical stability and bioactivity, suggesting their potential use in skeletal tissue regeneration and as coating onto currently available orthopedic/dental implants.