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Biomedical subjects

Aldo R Boccaccini

Publications and source records attributed to Aldo R Boccaccini.

At least 19 recordsLinked to original sources
PubMed2006

Polyhydroxyalkanoates in Gram-positive bacteria: insights from the genera Bacillus and Streptomyces.

Gram-positive bacteria, notably Bacillus and Streptomyces, have been used extensively in industry. However, these microorganisms have not yet been exploited for the production of the biodegradable polymers, polyhydroxyalkanoates (PHAs). Although PHAs have many potential applications, the cost of production means that medical applications are currently the main area of use. Gram-negative bacteria, currently the only commercial source of PHAs, have lipopolysaccharides (LPS) which co-purify with the PHAs and cause immunogenic reactions. On the other hand, Gram- positive bacteria lack LPS, a positive feature which justifies intensive investigation into their production of PHAs. This review summarizes currently available knowledge on PHA production by Gram- positive bacteria especially Bacillus and Streptomyces. We hope that this will form the basis of further research into developing either or both as a source of PHAs for medical applications.

Acyltransferases↗
PubMed2006

Evaluation of human bone marrow stromal cell growth on biodegradable polymer/bioglass composites.

Bone tissue engineering using human bone marrow mesenchymal stem cells (HBMCs) and biocompatible materials provides an attractive approach to regenerate bone tissue to meet the major clinical need. The aim of this study was to examine the effects of novel porous biodegradable composite materials consisting of a bioactive phase (45S5 Bioglass, 0, 5, and 40 wt%) incorporated within a biodegradable poly(dl-lactic acid) matrix, on HBMCs growth. Cell adhesion, spreading, and viability was examined using Cell Tracker Green/Ethidium Homodimer-1. Bone formation was assessed using scaffolds seeded with stro-1 positive HBMCs in nude mice. In vitro biochemistry indicated that with minimal scaffold pre-treatment osteoblast activity falls with increasing Bioglass content. However, 24h scaffold pre-treatment with serum resulted in a significant increase in alkaline phosphatase specific activity in 5 wt% Bioglass composites relative to the 0 and 40 wt% Bioglass groups. In vivo studies indicate significant new bone formation throughout all the scaffolds, as evidenced by immunohistochemistry.

Absorbable Implants↗
PubMed2006

Polyhydroxyalkanoate (PHA)/inorganic phase composites for tissue engineering applications.

Polyhydroxyalkanoates are emerging as a class of biodegradable polymers for applications in tissue engineering. Members of the polyhydroxyalkanoates family encompass a wide variety of materials, from hard and brittle materials to soft and elastomeric. Over the years, efforts have been made to extend the group of polyhydroxyalkanoates and to investigate their use in numerous biomedical applications, such as sutures, cardiovascular patches, wound dressings, guided tissue repair/regeneration devices, and tissue engineering scaffolds. Along with the development of polyhydroxyalkanoates, researchers have looked into the possibility of designing composites in combination with inorganic phases to further improve the mechanical properties, rate of degradation, and also impart bioactivity. Poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) are some of the polymers which have been studied extensively to fabricate composites in combination with hydroxyapatite, bioactive glass, and glass-ceramic fillers or coatings. This paper reviews international research carried out toward development of polyhydroxyalkanoates/inorganic phase composites in terms of systems investigated, microstructures, properties achieved, and applications, with special focus on tissue engineering scaffolds. A comparison between different composite systems developed in the past few years is presented. The paper also addresses the prospect of potential further development of polyhydroxyalkanoates/inorganic phase composites with optimized microstructure and properties for improved tissue engineering scaffolds.

Absorbable Implants↗
PubMed2006

Processing and characterization of porous structures from chitosan and starch for tissue engineering scaffolds.

Natural biodegradable polymers were processed by different techniques for the production of porous structures for tissue engineering scaffolds. Potato, corn, and sweet potato starches and chitosan, as well as blends of these, were characterized and used in the experiments. The techniques used to produce the porous structures included a novel solvent-exchange phase separation technique and the well-established thermally induced phase separation method. Characterization of the open pore structures was performed by measuring pore size distribution, density, and porosity of the samples. A wide range of pore structures ranging from 1 to 400 microm were obtained. The mechanisms of pore formation are discussed for starch and chitosan scaffolds. Pore morphology in starch scaffolds seemed to be determined by the initial freezing temperature/freezing rate, whereas in chitosan scaffolds the shape and size of pores may have been determined by the processing route used. The mechanical properties of the scaffolds were assessed by indentation tests, showing that the indentation collapse strength depends on the pore geometry and the material type. Bioactivity and degradation of the potential scaffolds were assessed by immersion in simulated body fluid.

Amylopectin↗
PubMed2006

Chondrogenic differentiation of human embryonic stem cells: the effect of the micro-environment.

We have previously induced differentiation of embryonic stem cells (ESC) to specific phenotypes by manipulating the culture conditions, including the use of indirect co-culture. In this study, we hypothesized that co-culture with primary chondrocytes can induce human embryonic stem cells (hESC) to differentiate towards the chondrocyte lineage. Co-cultures of hESC and chondrocytes were established using well inserts, with control comprising hESC grown alone or with fibroblasts. After 28 days, after removal of the chondrocyte inserts, hESC differentiation was assessed, by morphology, immunocytochemistry, and reverse transcription polymerase chain reaction. hESC, co-cultured or grown alone, were also implanted into SCID mice on a poly-D, L-lactide scaffold, harvested 35 days later and assessed in the same way. hESC co-cultured with chondrocytes formed colonies and secreted extracellular matrix containing glycosaminoglycans (GAG). Quantitative assay showed increased synthesis of sulfated GAG in co-culture as compared with control hESC grown alone for the same period (p < 0.0001). In addition, co-cultured hESC expressed Sox 9 and collagen type II, unlike control hESC. Co-culture with fibroblasts did not induce chondrogenic differentiation. The implanted constructs with co-cultured hESC contained significantly more type II collagen (p < 0.01), type I collagen (p < 0.05), total collagen (p < 0.01), and GAG (p < 0.01) than those with hESC grown alone. Thus, we show for the first time differentiation of hESC to chondrocytes. Our results confirm the potential of the culture micro-environment to influence ESC differentiation and could provide the basis for future generation of chondrogenic cells for use in tissue repair and increase our understanding of the mechanisms that direct differentiation.

Cell Differentiation↗
PubMed2005

In vitro and in vivo analysis of macroporous biodegradable poly(D,L-lactide-co-glycolide) scaffolds containing bioactive glass.

Recent studies have demonstrated the angiogenic potential of 45S5 Bioglass. However, it is not known whether the angiogenic properties of Bioglass remain when the bioactive glass particles are incorporated into polymer composites. The objectives of the current study were to investigate the angiogenic properties of 45S5 Bioglass particles incorporated into biodegradable polymer composites. In vitro studies demonstrated that fibroblasts cultured on discs consisting of specific quantities of Bioglass particles mixed into poly(D,L-lactide-co-glycolide) secreted significantly increased quantities of vascular endothelial growth factor. The optimal quantity of Bioglass particles determined from the in vitro experiments was incorporated into three-dimensional macroporous poly(D,L-lactide-co-glycolide) foam scaffolds. The foam scaffolds were fabricated using either compression molding or thermally induced phase separation processes. The foams were implanted subcutaneously into mice for periods of up to 6 weeks. Histological assessment was used to determine the area of granulation tissue around the foams, and the number of blood vessels within the granulation tissue was counted. The presence of Bioglass particles in the foams produced a sustained increase in the area of granulation tissue surrounding the foams. The number of blood vessels surrounding the neat foams was reduced after 2 weeks of implantation; however, compression-molded foams containing Bioglass after 4 and 6 weeks of implantation had significantly more blood vessels surrounding the foams compared with foams containing no Bioglass at the same time points. These results indicate that composite polymer foam scaffolds containing Bioglass particles retain granulation tissue and blood vessels surrounding the implanted foams. The use of this polymer composite for tissue engineering scaffolds might provide a novel approach for ensuring adequate vascular supply to the implanted device.

Angiogenesis Inducing Agents↗
PubMed2005

45S5 Bioglass-derived glass-ceramic scaffolds for bone tissue engineering.

Three-dimensional (3D), highly porous, mechanically competent, bioactive and biodegradable scaffolds have been fabricated for the first time by the replication technique using 45S5 Bioglass powder. Under an optimum sintering condition (1000 degrees C/1h), nearly full densification of the foam struts occurred and fine crystals of Na2Ca2Si3O9 formed, which conferred the scaffolds the highest possible compressive and flexural strength for this foam structure. Important findings are that the mechanically strong crystalline phase Na2Ca2Si3O9 can transform into an amorphous calcium phosphate phase after immersion in simulated body fluid for 28 days, and that the transformation kinetics can be tailored through controlling the crystallinity of the sintered 45S5 Bioglass. Therefore, the goal of an ideal scaffold that provides good mechanical support temporarily while maintaining bioactivity, and that can biodegrade at later stages at a tailorable rate is achievable with the developed Bioglass-based scaffolds.

Biocompatible Materials↗
PubMed2005

Effect of particulate bioactive glasses on human macrophages and monocytes in vitro.

Bioactive glasses, originally developed to promote tissue adhesion, are finding an increasing array of biomedical applications. The aim of the current study was to assess the ability of silicate- and zinc phosphate-based bioactive glasses to modulate the secretion of cytokines from activated human macrophages and monocytes. Human macrophages and monocytes were isolated and cultured on surfaces coated with a range of quantities of the bioactive glasses. Nontoxic concentrations of the glasses were selected and assessed further for their ability to modulate the secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-10 and -6, in the presence or absence of the stimulant lipopolysaccharide. 45S5 glass produced a significant reduction to the amount of TNF-alpha (p<0.05) and IL-6 (p<0.01) secreted by stimulated cells compared with cells stimulated in the absence of bioactive glass. A significant reduction in IL-6 secretion was also observed with the other silicate- and zinc phosphate-based glasses tested. IL-10 secretion was increased (but not significantly) in presence of all glasses tested. TNF-alpha and IL-6 secretion from stimulated cells was lower in presence of the silicate glasses compared with the zinc phosphate glasses, indicating that this system of bioactive glass might be of clinical use in conditions associated with inflammation.

Cells, Cultured↗
PubMed2005

Thermal Characterizations of silver-containing bioactive glass-coated Sutures.

This study utilized and compared a number of thermal analysis methods to characterize the thermal properties of commercial sutures with and without antimicrobial coatings of silver-doped bioactive glass (AgBG) interlocking particulates. The effect of a slurry dipping technique used to coat resorbable Vicryl (polyglactin 910) and non-resorbable Mersilk surgical sutures with AgBG was investigated using conventional differential scanning calorimetry (DSC), high speed calorimetry (or HYPERDSC), and modulated temperature DSC (MTDSC). These methods were compared in terms of their ability to resolve the thermal transitions of the types of suture materials. Differential thermal analysis (DTA) and thermogravimetric analysis (TGA) were used to verify the thermal degradation temperatures of these materials and to quantify the AgBG coatings on the sutures. The use of complementary thermal analysis techniques enabled the understanding of the effect of the AgBG coating technique on the morphological properties of the sutures. The slurry dipping technique had no significant effect on the thermal transitions of both types of materials. The use of high speed calorimetry through DSC offered better resolution for the transitions that appeared to be weak through conventional heating regimes, and was able to separate broad double transitions. Furthermore, it was shown not to compromise either the melting temperature or the enthalpy of melting. Therefore this method allows for the accurate determination of thermal transitions through much shorter experimental times thus allowing for an increased sample throughput. The combined DTA and TGA indicated that a greater AgBG coating was obtained in the case of the Mersilk sutures.

Coated Materials, Biocompatible↗
PubMed2005

Bioactive composite materials for tissue engineering scaffolds.

Synthetic bioactive and bioresorbable composite materials are becoming increasingly important as scaffolds for tissue engineering. Next-generation biomaterials should combine bioactive and bioresorbable properties to activate in vivo mechanisms of tissue regeneration, stimulating the body to heal itself and leading to replacement of the scaffold by the regenerating tissue. Certain bioactive ceramics such as tricalcium phosphate and hydroxyapatite as well as bioactive glasses, such as 45S5 Bioglass, react with physiologic fluids to form tenacious bonds with hard (and in some cases soft) tissue. However, these bioactive materials are relatively stiff, brittle and difficult to form into complex shapes. Conversely, synthetic bioresorbable polymers are easily fabricated into complex structures, yet they are too weak to meet the demands of surgery and the in vivo physiologic environment. Composites of tailored physical, biologic and mechanical properties as well as predictable degradation behavior can be produced combining bioresorbable polymers and bioactive inorganic phases. This review covers recent international research presenting the state-of-the-art development of these composite systems in terms of material constituents, fabrication technologies, structural and bioactive properties, as well as in vitro and in vivo characteristics for applications in tissue engineering and tissue regeneration. These materials may represent the effective optimal solution for tailored tissue engineering scaffolds, making tissue engineering a realistic clinical alternative in the near future.

Biocompatible Materials↗
PubMed2004

PDLLA/Bioglass composites for soft-tissue and hard-tissue engineering: an in vitro cell biology assessment.

The aim of this study was to examine the effect of increased content of 45S5 Bioglass (0-40 wt%) in poly(dl-lactic acid) (PDLLA) porous foams on the behaviour of MG-63 (human osteosarcoma cell line) and A549 cells (human lung carcinoma cell line). The ability of these cell lines to grow on bioactive composites was quantitatively investigated in order to assess the potentiality for their use in hard and soft-tissue engineering. Two hours after cell seeding, an increase of cell adhesion according to the increased content of Bioglass((R)) present in the foams for both cell types was observed. Cell proliferation studies performed over a period of 4 weeks showed a better aptitude of the A549 cells to proliferate on PDLLA foams containing 5 wt% Bioglass when compared to the proliferation on foams with 40 wt% Bioglass. A lower proliferation rate was obtained for cells on pure PDLLA. Scanning electron microscopy analysis showed for both cell types the presence of cells inside the porous structure of the foams. These results confirmed the biocompatibility of PDLLA/Bioglass composite foams and the positive effect of Bioglass on MG-63 cell behaviour and also showed for the first time the possibility for human lung epithelial type II cells to adhere and proliferate on these porous scaffolds. In addition, we describe a positive effect of 45S5 Bioglass on A549 cell behaviour in a dose-dependent manner, indicating the potential of using PDLLA/Bioglass composites with an optimal concentration of 45S5 Bioglass not only in bone tissue engineering but also in lung tissue engineering.

Biocompatible Materials↗
PubMed2004

Characterisation of bioactive and resorbable polylactide/Bioglass composites by FTIR spectroscopic imaging.

Formation, size and distribution of hydroxyapatite domains in resorbable composites made of poly(DL-lactide) foams and Bioglass particles after exposure to a solution of phosphate-buffer saline (PBS) for different periods of time have been analysed with FTIR imaging using the micro-ATR-IR approach. The spectral information of 4096 spectra measured simultaneously with the IR microscope equipped with a focal plane infrared array detector allowed us to obtain chemical images showing the distribution of Bioglass particles in the composites. FTIR imaging in micro-ATR mode allowed to obtain images with enhanced spatial resolution. A random distribution of hydroxyapatite domains with average size of ca. 10 microm on the surface of the composites was found after exposure to PBS for 14 and 28 days. The further growth of the hydroxyapatite domains after exposure to PBS for 63 days was detected. The spectroscopic imaging method introduced here promises to become a powerful method for characterisation of resorbable polymer composites containing bioactive inorganic phases developed for bone tissue engineering scaffolds. The accurate detection of hydroxyapatite domains and the imaging of their location in the scaffold structure is required to provide an assessment of the composites bioactivity.

Absorbable Implants↗
PubMed2004

Assessment of polyglycolic acid mesh and bioactive glass for soft-tissue engineering scaffolds.

Sufficient neovascularization of neotissue is currently a limiting factor for the engineering of large tissue constructs. 45S5 Bioglass has been investigated extensively in bone tissue engineering but there has been relatively little previous research on its application to soft-tissue engineering. The objectives of this study were to investigate the use of 45S5 Bioglass in soft-tissue engineering scaffolds using in vitro and in vivo models. A fibroblast cell line (208F) was used for in vitro evaluation of surfaces coated with 45S5 Bioglass. Increased proliferation of fibroblasts was observed after growth on polystyrene surfaces coated with low concentrations (0.01-0.2%wt/vol) of 45S5 Bioglass for 24 h in vitro, determined as a change in total cell number by measuring lactate dehydrogenase. At higher concentrations of 45S5 Bioglass and longer periods of incubation (48 and 72 h) on coated surfaces, cell proliferation was reduced. Light microscopy revealed that the morphology of fibroblasts grown on 45S5 Bioglass-coated surfaces was not altered at low concentrations, but at higher concentrations fibroblasts became vacuolated. Enzyme-linked immunosorbent assay of conditioned culture medium collected from fibroblasts grown for 24 h on surfaces coated with low concentrations of 45S5 Bioglass (0.01%wt/vol) was found to contain significantly higher concentrations of vascular endothelial growth factor. Histological examination of polyglycolic acid (PGA)/45S5 Bioglass composite scaffolds that had been implanted subcutaneously into rats revealed that 45S5 Bioglass-coated meshes were well tolerated. Light microscopy revealed that neovascularization into 45S5 Bioglass-coated meshes was significantly increased at 28 and 42 days. Electron microscopy revealed fibroblasts adhering closely to the PGA mesh but not to 45S5 Bioglass particles. The apparent ability of 45S5 Bioglass incorporated into scaffolds to increase neovascularization would be extremely beneficial during the engineering of larger soft-tissue constructs.

Animals↗
PubMed2004

In vivo characterisation of a novel bioresorbable poly(lactide-co-glycolide) tubular foam scaffold for tissue engineering applications.

Polylactide-co-glycolide (PLGA) foams of tubular shape were assessed for their use as soft-tissue engineering scaffolds in vitro and in vivo. Porous membranes were fabricated by a thermally induced phase separation process of PLGA solutions in dimethylcarbonate. The parameters investigated were the PLGA concentration and the casting volume of solution. Membranes produced from 5 wt/v % polymer solutions and a 6 ml casting volume of polymer solution were selected for fabricating tubes of 3 mm diameter, 20 mm length and a nominal wall thickness of 1.5 mm. Scanning electron microscopy revealed that the structure of the tubular foams consisted of radially oriented and highly interconnected pores with a large size distribution (50-300 microm). Selected tubes were implanted subcutaneously into adult male Lewis rats. Although the lumen of the tubes collapsed within one week of implantation, histological examination of the implanted scaffolds revealed that the foam tubes were well tolerated. Cellular infiltration into the foams, consisting mainly of fibrovascular tissue, was evident after two weeks and complete within eight weeks of implantation. The polymer was still evident in the scaffolds after eight weeks of implantation. The results from this study demonstrate that the PLGA tubular foams may be useful as soft-tissue engineering scaffolds with modification holding promise for the regeneration of tissues requiring a tubular shape scaffold such as intestine.

Absorbable Implants↗
PubMed2004

Bioactivity of degradable polymer sutures coated with bioactive glass.

Novel bioactive materials have been prepared by coating violet resorbable Vicryl sutures with a bioactive glass powder derived from a co-precipitation method. Two techniques have been chosen for the composite preparation: pressing the sutures in a bed of glass powder and slurry-dipping of sutures in liquid suspensions of bioactive glass powders. The uniformity and thickness of the coatings obtained by the two methods were compared. The bioactivity of the sutures with and without bioactive glass coating was tested by soaking in an inorganic acellular simulated body fluid (SBF). The composite sutures were characterised by XRD, SEM and FTIR analyses before and after soaking in SBF solution to assess the formation of hydroxyapatite on their surfaces, which is a qualitative measure of their bioactivity. The possible use of bioactive sutures to produce tissue engineering scaffolds and as reinforcement of resorbable calcium phosphates is discussed.

Absorbable Implants↗
PubMed2004

In vitro attachment of Staphylococcus epidermidis to surgical sutures with and without Ag-containing bioactive glass coating.

The ability of a silver-doped bioactive glass (AgBG) coating to prevent bacterial colonization on surgical sutures was investigated in vitro. Bioactive glass powders, in the form of 45S5 Bioglass and AgBG, were used to coat Mersilk sutures using an optimized 'in house' slurry-dipping process. In vitro experiments were carried out using Staphylococcus epidermidis under both batch and flow conditions. While the traditional batch culture testing was used to determine the number of viable cells adhered to the surface, the flow-cell was used to visualize attachment and detachment over time. Under batch conditions of up to 180 min, statistically significant differences were observed in the colony forming units (CFU) per suture for both the coated and uncoated Mersilk sutures. The results showed that the AgBG coating had the greatest effect on limiting bacterial attachment (8 x 10(2) CFU) when compared to the 45S5 Bioglass coating (3.2 x 10(3) CFU) and the uncoated Mersilk (1.2 x 10(4) CFU). Also under flow conditions differences were seen between the coated and uncoated sutures. Therefore, this preliminary study has demonstrated the quantification and visualization of bacterial attachment onto sutures in order to compare the antibacterial properties of Ag-containing bioactive glass coatings. The bactericidal properties imparted by Ag-containing glass open new opportunities for use of the composite sutures in wound healing and body wall repair.

Bacterial Adhesion↗
PubMed2003

Composite surgical sutures with bioactive glass coating.

A processing method was developed to coat polyglactin 910 (Vicryl) sutures with bioactive glass powder (45S5 Bioglass). High reproducibility and homogeneity of the coating in terms of microstructure and thickness along the suture length were achieved. Bioglass-coated sutures exhibited a high level of chemical reactivity in simulated body fluid (SBF), indicating their bioactive behavior. This was evident by the prompt formation of hydroxyapatite (HA) crystals on the surface after only 7 days of immersion in SBF. These crystals grew to form a thick HA layer (15 microm thickness) after 3 weeks in SBF. The tensile strength of the sutures was tested before and after immersion in SBF in order to assess the effect of the bioactive glass coating on suture degradation. The tensile strength of composite sutures was lower than that of as-received Vicryl sutures, 385 and 467 MPa, respectively. However, after 28 days of immersion in SBF the residual tensile strengths of coated and uncoated sutures were similar (83 and 88 MPa, respectively), indicating no negative effect of the HA layer formation on the suture strength. The effect of bioactive glass coating on the polymer degradation is discussed. The developed bioactive sutures represent interesting materials for applications in wound healing, fabrication of fibrous three-dimensional scaffolds for tissue engineering, and reinforcement elements for calcium-phosphate temporary implants.

Body Fluids↗