Range Of Cancellous Bone Research Articles

Fabrication of magnetic nanocomposite scaffolds based on polyvinyl alcohol-chitosan containing hydroxyapatite and clay modified with graphene oxide: Evaluation of their properties for bone tissue engineering applications

One of the most common systems for bone tissue engineering is polymeric scaffolds. However, the low mechanical properties of polymeric scaffolds, considering the properties required for bone replacement tissue, are the main challenge for researchers in this field. For bone tissue engineering, this research prepared nanocomposite scaffolds based on polyvinyl alcohol-chitosan containing modified clay and hydroxyapatite (HAp). HAp used in these 3D scaffolds was synthesized from a chicken femur, and Cloisite 30B clay nanoparticles were modified by graphene oxide and Fe3O4 nanoparticles to strengthen their mechanical properties. Sample characteristics were determined using FT-IR, XRD, SEM, TGA, swelling rate, laboratory degradation, and biological and mechanical properties. These analyses showed that 2% of modified clay (C30B/GO/Fe3O4, CGF) inside the nanocomposite scaffold increased the compressive strength 23 times compared to the pristine polymer scaffold. Also, adding HAp particles and modified clay simultaneously increased the mineralization on the surface of the scaffolds. Final nanocomposite scaffolds were found to have a compressive strength of 9.31 MPa, a porosity of 75 %, and a porosity size of 50 nm and were in the range of cancellous bone. The final swelling amount is 1790 %, which is the amount that is Favorable for bone scaffold. Finally, the analysis results to determine the samples' toxicity showed that none of the prepared scaffolds were toxic and showed good cell viability.

Antibacterial and angiogenic potential of iron oxide nanoparticles-stabilized acrylate-based scaffolds for bone tissue engineering applications

Pickering emulsion polymerization, stabilized by inorganic nanoparticles such as iron oxide nanoparticles (IONPs), can be used to fabricate scaffolds with the desired porosity and pore size. These nanoparticles create stable emulsions that can be processed under harsh polymerization conditions. IONPs, apart from serving as an emulsifier, impart beneficial bioactivities such as antibacterial and pro-angiogenic activity. Here, we coated IONPs with three different weights of oleic acid (5.0 g, 7.5 g, and 10.0 g) to synthesize oleic acid-IONPs (OA-IONPs) that possess the desired hydrophobicity (contact angle > 100°). Next, glycidyl methacrylate and trimethylolpropane triacrylate were polymerized using the Pickering emulsion polymerization technique stabilized by the OA-IONPs. The physicochemical properties of the resulting porous scaffolds were thoroughly characterized using scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometry (VSM), and a universal testing machine (UTM). The SEM images confirmed the formation of a porous scaffold. The IONPs content, measured using inductively coupled plasma mass spectrometry (ICP-MS), was in the range of 22–26 µg/mg of the scaffold. The mechanical strengths of the scaffolds were in the range of cancellous bone. The degradation profile of the scaffolds varied between 29% and 41% degradation over 30 days. In vitro cytotoxicity studies conducted using the fibroblast (L929) and osteosarcoma (MG-63) cell lines proved that these scaffolds were non-toxic. SEM images showed that the MG-63 cells adhered firmly to the scaffolds and exhibited a well-spread morphology. The antibacterial activity was confirmed by percentage inhibition studies, SEM analysis of bacterial membrane distortion, and reactive oxygen species (ROS) generation in the bacteria. Chick chorioallantoic membrane assay showed that the total vessel length and branch points were significantly increased in the presence of the scaffolds. These results confirm the pro-angiogenic potential of the fabricated scaffolds. The physicochemical, mechanical, and biological properties of the material suggest that the developed scaffolds would be suitable for bone tissue engineering applications.

Impact of residual carbon after DLP and SPS-Sintering on compressive strength and in-VITRO bioactivity of calcium phosphate scaffolds

Digital Light Processing was used to fabricate bioactive ceramic scaffolds for bone regeneration using β-tricalcium phosphate (β-TCP) powder as a starting material. The 3D structures were de-binded in vacuum and divided in two batches: Carbon Containing samples and Carbon Free samples (obtained by firing at 750 °C in air after de-binding). All samples were then sintered in pressure-less SPS either at 1200 °C or 1500 °C, resulting in two different polymorphs (β and α -TCP). The influence of the de-binding method, the in-situ formation of a carbonaceous phase and different phase composition of resulting scaffolds was evaluated in terms of mechanical performance and in vitro bioactivity and solubility in simulated body fluid (SBF). All scaffolds exhibited compressive strengths within the range of cancellous bone and bone-like apatite precipitates were visible on their surface after 21 days of immersion in SBF, with the exception of carbon-free samples sintered at 1200 °C.

One-step preparation of functionally hierarchical and structurally hierarchical biomimetic bioceramics composed of porous hydroxyapatite and carbon fiber reinforced hydroxyapatite composites

Based on human bone structure characteristics and from the perspective of bionics, we designed and constructed hierarchical bioceramics which included porous hydroxyapatite (PHA) providing better bioactive functionality and carbon fiber (CF) reinforced hydroxyapatite (CF/HA) biocomposites with strengthened mechanical properties from the center to the outer part via one-step preparation. The effects of pore forming agent (NH4HCO3) and temperatures on the morphology, mechanical performance, biological properties were studied. The pore sizes of PHA were basically distributed from 20 μm to 200 μm. With the increase of NH4HCO3 contents, both the total number of the pores and interconnected pores increased, and internally connected small micropores were produced among the large pores. The compressive strength of PHA with 30 wt% NH4HCO3 (30%PHA) sintered at 1130 °C was 27.74 ± 0.52 MPa, which lay in the range of cancellous bone. In the hierarchical bioceramics, the interface between the PHA and CF/HA composites was so well bonded that it can be hardly distinguish the different regions in cross-section. The compressive strength of hierarchical bioceramics was 35.43 MPa, which increased by 27.7% compared with 30%PHA. Fracture toughness from the center to the outer part of the ceramics was 0.70 ± 0.15 MPa m1/2 and 1.37 ± 0.29 MPa m1/2, respectively. The high porosity favored the formation of apatite layer and improved the bioactivity compared with the dense hydroxyapatite (HA). The results of the expression of osteogenic genes (BMP2, Runx2, Opn and Ocn) detected by real-time PCR showed that the 30%PHA was positive to bone development. In vivo study indicated that the implanted PHA contributed to the ingrowth of more new bone tissue. This hierarchical bioceramics possess not only the enhanced mechanical properties but also excellent bioactivity and osteogenic properties. The study provides a promising biomimetic hierarchical bone repair materials which can tailor mechanical properties and bioactive functionality via simply adjusting constitution of CF reinforced and porous bioceramics.

Extrusion-based 3D printing of ex situ-alloyed highly biodegradable MRI-friendly porous iron-manganese scaffolds

Additively manufactured biodegradable porous iron has been only very recently demonstrated. Two major limitations of such a biomaterial are very low biodegradability and incompatibility with magnetic resonance imaging (MRI). Here, we present a novel biomaterial that resolves both of those limitations. We used extrusion-based 3D printing to fabricate ex situ-alloyed biodegradable iron-manganese scaffolds that are non-ferromagnetic and exhibit enhanced rates of biodegradation. We developed ink formulations containing iron and 25, 30, or 35 wt% manganese powders, and debinding and sintering process to achieve Fe-Mn scaffolds with 69% porosity. The Fe25Mn scaffolds had the ε-martensite and γ-austenite phases, while the Fe30Mn and Fe35Mn scaffolds had only the γ-austenite phase. All iron-manganese alloys exhibited weakly paramagnetic behavior, confirming their potential to be used as MRI-friendly bone substitutes. The in vitro biodegradation rates of the scaffolds were very much enhanced (i.e., 4.0 to 4.6 times higher than that of porous iron), with the Fe35Mn alloy exhibiting the highest rate of biodegradation (i.e., 0.23 mm/y). While the elastic moduli and yield strengths of the scaffolds decreased over 28 days of in vitro biodegradation, those values remained in the range of cancellous bone. The culture of preosteoblasts on the porous iron-manganese scaffolds revealed that cells could develop filopodia on the scaffolds, but their viability was reduced by the effect of biodegradation. Altogether, this research marks a major breakthrough and demonstrates the great prospects of multi-material extrusion-based 3D printing to further address the remaining issues of porous iron-based materials and, eventually, develop ideal bone substitutes. Statement of significance3D printed porous iron biomaterials for bone substitution still encounter limitations, such as the slow biodegradation and magnetic resonance imaging incompatibility. Aiming to solve the two fundamental issues of iron, we present ex-situ alloyed porous iron-manganese scaffolds fabricated by means of multi-material extrusion-based 3D printing. Our porous iron-manganese possessed enhanced biodegradability, non-ferromagnetic property, and bone-mimicking mechanical property throughout the in vitro biodegradation period. The results demonstrated a great prospect of multi-material extrusion-based 3D printing to further address the remaining challenges of porous iron-based biomaterials to be an ideal biodegradable bone substitutes.

Scaffold-Dependent Mechanical and Architectural Cues Guide Osteochondral Defect Healing in silico.

Osteochondral defects in joints require surgical intervention to relieve pain and restore function. However, no current treatment enables a complete reconstitution of the articular surface. It is known that both mechanical and biological factors play a key role on osteochondral defect healing, however the underlying principles and how they can be used in the design of treatment strategies remain largely unknown. To unravel the underlying principles of mechanobiology in osteochondral defect healing, i.e., how mechanical stimuli can guide biological tissue formation, we employed a computational approach investigating the scaffold-associated mechanical and architectural properties that would enable a guided defect healing. A previous computer model of the knee joint was further developed to simulate healing of an empty osteochondral defect. Then, scaffolds were implanted in the defect and their architectures and material properties were systematically varied to identify their relevance in osteochondral defect healing. Scaffold mechanical and architectural properties were capable of influencing osteochondral defect healing. Specifically, scaffold material elastic modulus values in the range of cancellous bone (low GPa range) and a scaffold architecture that provided stability, i.e., resistance against displacement, in both the main loading direction and perpendicular to it supported the repair process. The here presented model, despite its simplifications, is regarded as a powerful tool to screen for promising properties of novel scaffold candidates fostering osteochondral defect regeneration prior to their implementation in vivo.

Processing of Sr2+ Containing Poly L-Lactic Acid-Based Hybrid Composites for Additive Manufacturing of Bone Scaffolds

Biodegradable composite materials represent one of the major areas of investigation for bone tissue engineering due to their tuneable compositional and mechanical properties, which can potentially mimic those of bone and potentially avoid the removal of implants, mitigating the risks for the patient and reducing the overall clinical costs. In addition, the introduction of additive manufacturing technologies enables a strict control over the final morphological features of the scaffolds. In this scenario, the optimisation of 3D printable resorbable composites, made of biocompatible polymers and osteoinductive inorganic phases, offers the potential to produce a chemically and structurally biomimetic implant, which will resorb over time. The present work focuses on the development and process optimisation of two hybrid composite filaments, to be used as feedstock for the fused filament fabrication 3D printing process. A Poly L-lactic acid matrix was blended with either rod-like nano-hydroxyapatite (nano-HA) or nanoparticles of mesoporous bioactive glasses, both partially substituted with strontium (Sr2+), due to the well-known pro-osteogenic effect of this ion. Both inorganic phases were incorporated into Poly L-lactic acid using an innovative combination of processes, obtaining a homogeneous distribution throughout the polymer whilst preserving their ability to release Sr2+. The filament mechanical properties were not hindered after the incorporation of the inorganic phases, resulting in tensile strengths and moduli within the range of cancellous bone, 50 ± 10 MPa and 3 ± 1 GPa. Finally, the rheological characterization of the hybrid composites indicated a shear thinning behaviour, ideal for the processing with fused filament fabrication, proving the potential of these materials to be processed into 3D structures aiming bone regeneration.

3D printed bioactive and antibacterial silicate glass-ceramic scaffold by fused filament fabrication

The fused filament fabrication (FFF) technique was applied for the first time to fabricate novel 3D printed silicate bioactive and antibacterial Ag-doped glass-ceramic (Ag-BG) scaffolds. A novel filament consisting primarily of polyolefin and Ag-BG micro-sized particles was developed and its thermal properties characterized by thermogravimetric analysis (TGA) to define the optimum heat treatment with minimal macrostructural deformation during thermal debinding and sintering. Structural characteristics of the Ag-BG scaffolds were evaluated from macro- to nanoscale using microscopic and spectroscopic techniques. The compressive strength of the Ag-BG scaffolds was found to be in the range of cancellous bone. Bioactivity of the 3D printed Ag-BG scaffolds was evaluated in vitro through immersion in simulated body fluid (SBF) and correlated to the formation of an apatite-like phase. Methicillin-resistant Staphylococcus aureus (MRSA) inoculated with the Ag-BG scaffolds exhibited a significant decrease in viability underscoring a potent anti-MRSA effect. This study demonstrates the potential of the FFF technique for the fabrication of bioactive 3D silicate scaffolds with promising characteristics for orthopedic applications.

One pot method to synthesize three-dimensional porous hydroxyapatite nanocomposite for bone tissue engineering

A three-dimensional porous hydroxyapatite nanocomposite has been synthesized by a simple, less energy consuming and cost effective one-pot method. In this study, gelatin foam has been used as pore forming agent and incorporated in carboxymethyl cellulose-hydroxyapatite system in composite formation stage. A three-dimensional porous polymers-hydroxyapatite nanocomposite has been formed as a final product. The synthesized porous nanocomposite has been thoroughly characterized by different techniques. It was found that the nanocomposite is highly porous with almost 80% porosity, and has multi-scale pores from 2.5 to 900 μm in size. Furthermore, the synthesized porous composite has compressive strength ~ 11.8 ± 1.5 MPa and modulus ~ 0.243 ± 0.031 GPa, in the range of cancellous bone. Moreover, the nanocomposite provides favorable environment to cells for proliferation, high alkaline phosphatase (ALP) activity and extracellular mineralization. In vitro degradation of synthesized nanocomposites was tested in simulated body fluid. Results ascertained that the synthesized porous hydroxyapatite nanocomposite would be a promising scaffold for bone tissue engineering.

Three-dimensional cellulose-hydroxyapatite nanocomposite enriched with dexamethasone loaded metal–organic framework: a local drug delivery system for bone tissue engineering

Three-dimensional cellulose-hydroxyapatite nanocomposite integrated with dexamethasone loaded metal organic framework (HA/DMOF) has been synthesized as a local drug delivery system for bone tissue engineering. Initially, in situ dexamethasone encapsulated metal–organic frameworks (DMOFs) were developed and characterized. The synthesized DMOFs are 60–80 nm in size with rhombohedral morphology. Results showed that nearly 16% dexamethasone (Dex) was loaded in DMOFs. These synthesized DMOF nanoparticles were efficiently integrated with carboxymethyl cellulose-hydroxyapatite nanocomposite for the development of three dimensional localized drug delivery system, namely, HA/DMOF. The synthesized HA/DMOF nanocomposite was structurally characterized using various techniques. The mechanical properties of HA/DMOFs were also measured by means of compression test. It was found that the compressive strength and compressive modulus of HA/DMOF nanocomposite are 16.3 ± 1.57 MPa and 0.54 ± 0.073 GPa respectively, which are in the range of cancellous bone. In-vitro release behaviour of Dex from both DMOFs and HA/DMOFs was examined in phosphate buffered solution. It was found that Dex molecules have been released very slowly from HA/DMOF nanocomposite compared to DMOF nanoparticles, and it was sustained for 4 weeks. Cytocompatibility of HA/DMOF nanocomposite was evaluated against pre-osteoblast MC3T3 cells. It was found that the synthesized HA/DMOF nanocomposite is compatible to MC3T3 cells. Moreover, the ALP activity and extracellular mineralization capability of cells were enhanced when cultured with HA/DMOF nanocomposite. Results showed that the synthesized HA/DMOF nanocomposite is a promising material for possible therapeutic as well as load-bearing orthopedic applications.

Preparation and characterization of gelatin-bioactive glass ceramic scaffolds for bone tissue engineering

Macroporous composite scaffolds comprising of gelatin and glass ceramic has been fabricated and characterized for bone tissue engineering applications. Gelatin scaffold with varying glass-ceramic content was fabricated using lyophilization technique. The microstructure, compressive strength, bioactivity, biodegradation and biocompatibility of the fabricated scaffolds were evaluated. The scaffolds presented macroporous pore size with porosity varying from 79 to 84%. The compressive strength was enhanced by glass ceramic addition and the scaffolds exhibited strength in the range of 1.9 to 5.7 MPa. The obtained strength and porosity was in the range of cancellous bone. The dissolution of gelatin scaffolds was optimized by an additional in situ glutaraldehyde crosslinking step and further by glass-ceramic addition. The composite scaffolds showed good apatite-forming ability in vitro. Biocompatibility and osteogenic ability of the scaffolds were analyzed in vitro by cell adhesion study, alkaline phosphatase activity and Alizarin S staining. The obtained results revealed the composite scaffolds possessed enhanced osteogenic ability and good cell adhesion properties. The developed scaffold is a prospective candidate as a biomaterial for bone tissue engineering.

Trigonella foenum graecum seed polysaccharide coupled nano hydroxyapatite-chitosan: A ternary nanocomposite for bone tissue engineering

Biomimetic nanocomposites containing hydroxyapatite and natural polymers are promising candidates for bone grafting. In this work, a tricomponent bioactive nanocomposite (nHA-CH-TFSP) assembling nano-hydroxyapatite (nHA), Chitosan (CH) and Trigonella foenum graecum seed polysaccharide (TFSP) was developed using co-precipitation method and investigated against bicomponent nHA-CH nanocomposite for bone tissue engineering. In contrast to nHA-CH nanocomposite, nHA-CH-TFSP nanocomposite exhibited rough and interconnected porous structure as revealed by SEM with the porosity (60.3 ± 0.17) lying in the range of cancellous bone. The incorporation of TFSP in nHA-CH substantially enhanced the in vitro water absorption capacity and protein adsorption ability along with appropriate biodegradation rate. Additionally, the nHA-CH-TFSP nanocomposite exhibited superior antibacterial activity. The nHA-CH-TFSP evinced a compressive strength of 6.7 ± 0.24 MPa and a compressive modulus of 100 ± 1.4 MPa, which fulfill the strength requisite of cancellous bone and could provide strong support for the growth of osteoblasts cells. Furthermore, the in vitro bioactivity study demonstrated its excellent biomineralization capacity in comparison to nHA-CH. The synthesized nHA-CH-TFSP nanocomposite exhibited better cytocompatibility towards the MG-63 cells along with its haemocompatible nature. Taken together the results of the present study indicate that nHA-CH-TFSP could serve as a prospective analogue for bone tissue engineering.

3D powder printed tetracalcium phosphate scaffold with phytic acid binder: fabrication, microstructure and in situ X-Ray tomography analysis of compressive failure.

One of the important aspects in 3D powder printing (3DPP) is the selection of binder for a specific material composition to produce scaffolds with desired microstructure and physico-chemical properties. To this end, a new powder-binder combination, namely tetracalcium phosphate (TTCP) and phytic acid (IP6) was investigated at ambient temperature, for low load bearing application. A minimal deviation (<200 µm, w.r.t. computer aided design) was observed in the final sample through optimization of 3DPP process, along with minimum strut and macro-pore size of 200 and 750 µm, respectively. Importantly, the printed scaffolds exhibited compressive strength of 4-8.5 MPa (in the range of cancellous bone) and in vitro dissolution experiments in phosphate buffered saline (PBS) upto one month revealed gradual degradation in strength property. The TTCP scaffolds are characterized to be moderately porous (~40%) with high interconnectivity, which is essential for vascularization and good osteoconductivity. Another major aim of this study was to demonstrate the failure mechanism of 3D powder-printed scaffolds using monotonic and intermittent compression coupled with micro-computed tomography (µCT) imaging. Analyzing these results, we have demonstrated the origin of crack generation and propagation under compressive loading in relation to the unique microstructure, obtained through 3DPP. These findings enable us to acquire a deeper insight of the relationship between structural attributes and failure behavior, to further tailor the 3D powder printing process for ceramic biomaterials.

Effect of freezing conditions on β-Tricalcium Phosphate /Camphene scaffold with micro sized particles fabricated by freeze casting

The long standing need of the implant manufacturing industries is to fabricate multi-matrix, customized porous scaffold as cost-effectively. In recent years, freeze casting has shown greater opportunity in the fabrication of porous scaffolds (tricalcium phosphate, hydroxyapatite, bioglass, alumina, etc.) such as at ease and good control over pore size, porosity, a range of materials and economic feasibility. In particular, tricalcium phosphate (TCP) has proved as it possesses good biocompatible (osteoinduction, osteoconduction, etc.) and biodegradability hence beta-tricalcium phosphate (β-TCP, particle size of 10µm) was used as base material and camphene was used as a freezing vehicle in this study. Both freezing conditions such as constant freezing temperature (CFT) and constant freezing rate (CFR) were used for six different conditional samples (CFT: 30, 35 and 40vol% solid loading; similarly CFR: 30, 35 and 40vol% solid loading) to study and understand the effect of various properties (pore size, porosity and compressive strength) of the freeze-cast porous scaffold. It was observed that the average size of the pore was varying linearly as from lower to higher when the solid loading was varying higher to lower. With the help of scanning electron micrographs (SEM), it was observed that the average size of pore during CFR (9.7/ 6.5/ 4.9µm) was comparatively higher than the process of CFT (6.0/ 4.8/ 2.6µm) with respect to the same solid loading (30/ 35/ 40vol%) conditions. From the Gas pycnometer analysis, it was found that the porosity in both freezing conditions (CFT, CFR) were almost near values such as 32.8% and 28.5%. Further to be observed that with the increase in solid loading, the total porosity value has decreased due to the reduction in the concentration of the freezing vehicle. Hence, the freezing vehicle was found as responsible for the formation of appropriate size and orientation of pores during freeze casting. The compressive strength (CS) testing was clearly indicated that the CS was majorly depending on the size of pore which was depending on solid loading. The CS of CFT-based samples (smaller pore sizes and higher resistance to the propagation of crack) were higher due to the higher solid content (pore size) in compared with CFR-based samples on the similar solid loading conditions. As evidently, it was noted that the CFT-based sample with 40% solid loading has given the compressive strength which has come in the range of cancellous bone. The positive note was that the ratio of Ca/P has come as 1.68 (natural bone) after sintering and that was the required value recommended by the food and drug administration (FDI) for manufacturing of bone implants.

Biodegradable and adjustable sol-gel glass based hybrid scaffolds from multi-armed oligomeric building blocks.

Adaption of degradation kinetics toward physiological relevance is still an unmet challenge of (bio-)glass engineering. We therefore present a glass-derived hybrid material with adjustable degradation. A flexible design concept based on degradable multi-armed oligomers was combined with an established indirect rapid prototyping method to produce a systematic set of porous sol-gel-derived class II hybrid scaffolds. Mechanical properties in the range of cancellous bone were narrowly controlled by hybrid composition. The oligoester introduction resulted in significantly increased compressive moduli. Cytocompatible hybrids degraded in physiologically relevant time frames and a promising linear and controllable weight loss profile was found. To our knowledge, our degradation study represents the most extensive long-term investigation of sol-gel-derived class II hybrids. Due to the broad adjustability of material properties, our concept offers potential for engineering of biodegradable hybrid materials for versatile applications.

Synthesis, Characterization and in-vitro Study of Chitosan/Gelatin/Calcium Phosphate Hybrid Scaffolds Fabricated Via Ion Diffusion Mechanism for Bone Tissue Engineering

In this study, biomimetic scaffolds were designed to investigate calcium phosphate formation via a double diffusion mechanism within a gelatin/chitosan hydrogel in biological pH and temperature. Three types of samples with initial percentages of chitosan (20, 30 and 40 wt. %) were prepared. Diffusion of calcium and phosphate ions through the hydrogel formed a precipitation layer. Samples were freeze dried to form porous scaffolds and soaked in glutaraldehyde to increase their mechanical properties. X-ray diffraction (XRD), Fourier transform infra-red (FTIR) spectroscopy and scanning electron microscopy (SEM) were employed to investigate the microstructure and to characterize the prepared scaffolds. Analysis of precipitation indicated the presence of brushite and hydroxyapatite. The amorphous calcium phosphate phase converted into crystalline hydroxyapatite after immersion in simulated body fluid which mimics the formation of hydroxyapatite in the human body. FTIR results suggested the presence of structural hydroxyl and phosphate bonds in the structure of the prepared scaffolds which could be due to the formation of hydroxyapatite. With increasing amount of chitosan in the composite scaffold, the water up-take ability was increased from 380 to 660 %, yield strength and Young’s modulus slightly decreased and the crystalinity of the precipitated phase increased. Mechanical properties obtained from the samples were in the range of cancellous bone. MTT assay results and alkaline phosphatase activity showed prepared scaffolds had proper biocompatibility.

Bioactive glass scaffolds for bone regeneration and their hierarchical characterisation

Scaffolds are needed that can act as temporary templates for bone regeneration and actively stimulate vascularized bone growth so that bone grafting is no longer necessary. To achieve this, the scaffold must have a suitable interconnected pore network and be made of an osteogenic material. Bioactive glass is an ideal material because it rapidly bonds to bone and degrades over time, releasing soluble silica and calcium ions that are thought to stimulate osteoprogenitor cells. Melt-derived bioactive glasses, such as the original Bioglass composition, are available commercially, but porous scaffolds have been difficult to produce because Bioglass and similar compositions crystallize on sintering. Sol-gel foam scaffolds have been developed that avoid this problem. They have a hierarchical pore structure comprising interconnected macropores, with interconnect diameters in excess of the 100 microm that is thought to be needed for vascularized bone ingrowth, and an inherent nanoporosity of interconnected mesopores (2-50 nm) which is beneficial for the attachment of osteoprogenitor cells. They also have a compressive strength in the range of cancellous bone. This paper describes the optimized sol-gel foaming process and illustrates the importance of optimizing the hierarchical structure from the atomic through nano, to the macro scale with respect to biological response.

Calcium phosphate cement composites in revision hip arthroplasty

Loosening of the femoral component in a total hip arthroplasty with concomitant bone loss can pose a problem for revision surgery due to inadequate structure in the remaining femur. While impaction allografting has shown promise, it has also shown serious complications, especially with moderate to severe bone loss. It may be possible to stabilize the graft layer with a bioresorbable cement to improve clinical results. This study examines the mechanical properties of a potential morsellized bone-bioresorbable composite. Morsellized bone was mixed with a commercially available bioresorbable cement ( α-BSM, Etex Corp.) in compositions of 0%, 25%, 50% and 75% bone. Unconfined compression and diametral tensile and confined compression tests were performed to determine the composite mechanical properties. The composition containing 50% bone tended to exhibit the highest uniaxial strengths, as well as the highest confined compression modulus. The uniaxial compressive strength and stiffness of this composition was in the range of cancellous bone. Uniaxial compressive modulus decreased with increasing bone fraction whereas elongation exhibited the opposite trend. Bone fraction had a significant effect on compressive strength ( p<0.0001), compressive modulus ( p<0.0001), elongation ( p<0.01), tensile strength ( p<0.0001) and confined compressive modulus ( p=0.04). The addition of a bioresorbable cement to the allograft layer may improve the properties of the layer, preventing early subsidence seen in some clinical studies of impaction allografting, and therefore improving the clinical results. Further testing is required to evaluate the in vitro mechanical performance, as well as in vivo remodelling characteristics.

Induction of Ectopic Bone Formation by Using Human Periosteal Cells in Combination with a Novel Scaffold Technology

Due to their osteogenic germination potential, periosteum-derived osteoprogenitor cells are a potential source for tissue engineering a bone graft that could be used to regenerate skeletal defects. In this study we evaluated if ectopic bone formation could be induced by a construct made of human periosteal cells and a novel scaffold architecture whose mechanical properties are in the range of cancellous bone. Biopsies from human calvarial periosteum were harvested and cells were isolated from the inner cambial layer. Fifty thousand periosteal cells were seeded into the scaffolds measuring 6 x 6 x 2 mm. The cell-scaffold constructs were cultured for a period of 3 weeks prior to implantation into balb C nude mice. Mice were sacrificed and implants were analyzed 6 and 17 weeks postoperatively. Immunohistochemical analysis confirmed the osteoblastic phenotype of the seeded cells. Formation of focal adhesions and stress fibers could be observed in both scaffold architectures. Three-dimensional cell proliferation was observed after 2 weeks of culturing with centripetal growth pattern inside the pore network. The deposition of calcified extracellular matrix was observed after 3 weeks of culturing. In vivo, endochondral bone formation with osteoid production was detectable via von Kossa and Osteocalcin staining after 6 and 17 weeks. Histology and SEM revealed that the entire scaffold/bone grafts were penetrated by a vascular network. This study showed the potential of bone tissue engineering by using human periosteal cells in combination with a novel scaffold technology.