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Major limitations of calcium phosphate cements (CPCs) are their relatively slow degradation rate and the lack of macropores allowing the ingrowth of bone tissue. The development of self-setting cement foams has been proposed as a suitable strategy to overcome these limitations. In previous work we developed a gelatine-based hydroxyapatite foam (G-foam), which exhibited good injectability and cohesion, interconnected porosity and good biocompatibility in vitro. In the present study we evaluated the in vivo performance of the G-foam. Furthermore, we investigated whether enrichment of the foam with soybean extract (SG-foam) increased its bioactivity. G-foam, SG-foam and non-foamed CPC were implanted in a critical-size bone defect in the distal femoral condyle of New Zealand white rabbits. Bone formation and degradation of the materials were investigated after 4, 12 and 20weeks using histological and biomechanical methods. The foams maintained their macroporosity after injection and setting in vivo. Compared to non-foamed CPC, cellular degradation of the foams was considerably increased and accompanied by new bone formation. The additional functionalization with soybean extract in the SG-foam slightly reduced the degradation rate and positively influenced bone formation in the defect. Furthermore, both foams exhibited excellent biocompatibility, implying that these novel materials may be promising for clinical application in non-loaded bone defects., (Copyright © 2014 Acta Materialia Inc. All rights reserved.)

Purpose: Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model., Methods: In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted., Results: Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration., Conclusions: None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioning.

Chronic and acute wounds can be quickly contaminated and infected by microorganisms such as bacteria, multi-resistant organisms or fungi. The introduction of silver as anti-microbial agent into wound management has widely been demonstrated to be effective and contribute to wound healing. As a consequence, many approaches and different materials have been employed to synthesize antibacterial silver-hydrogels. In this work the introduction of silver particles into the fibrillar structure of self-assembling aromatic di-phenylalanine derivatives modified with aromatic groups such as 9-fluorenylmethoxycarbonyl is proposed to produce antibacterial wound dressings. Hydrogels doped with increasing amounts of silver were tested and adopted to modify flax textiles. The influence of silver on the structure of hydrogels was studied using light and confocal microscopy, while SEM-EDX allowed the characterization of the hydrogel coating on the surface of the textile substrates as well as the identification and distribution of silver nanoparticles. The antibacterial potential of the treated flax was demonstrated through microbiological tests on Staphylococcus aureus. The combination of the physico-chemical and anti-bacterial properties, together with the ease of preparation of these biomaterials, fulfils the requirement of clinically-effective wound dressings.

The successful regeneration of large defects in traumatized and diseased tissues depends on the availability of biodegradable and bioactive biomaterials able to guide the tissue during its repair by offering both a physical support and a control of its biological mechanisms. Recently, a novel class of natural, biodegradable biomaterials has been obtained by the thermosetting of defatted soy curd. These biomaterials have been shown to regulate the activity of both tissue and inflammatory cells. Here, soybean-based hydrogels with different physicochemical properties and bioactivity have been obtained with a relatively simple and highly reproducible processing method. The content of the different soy components (e.g., the isoflavones) was tuned varying the solvent system during the extraction procedure, while variations in the material crosslinking provided either loose hydrogels or a bioglue. The biomaterials obtained can be used as either bioadhesives or injectable formulations in regenerative medicine as they were shown to stimulate the synthesis of collagen by fibroblasts and the formation of mineralized bone noduli by osteoblasts.

Despite their known osteoconductivity, clinical use of calcium phosphate cements is limited both by their relatively slow rate of resorption and by rheological properties incompatible with injectability. Bone in-growth and material resorption have been improved by the development of porous calcium phosphate cements. However, injectable formulations have so far only been obtained through the addition of relatively toxic surfactants. The present work describes the response of osteoblasts to a novel injectable foamed bone cement based on a composite formulation including the bioactive foaming agents soybean and gelatine. The foaming properties of both defatted soybean and gelatine gels were exploited to develop a self-hardening soy/gelatine/hydroxyapatite composite foam able to retain porosity upon injection. After setting, the foamed paste produced a calcium-deficient hydroxyapatite scaffold, showing good injectability and cohesion as well as interconnected porosity after injection. The intrinsic bioactivity of soybean and gelatine was shown to favour osteoblast adhesion and growth. These findings suggest that injectable, porous and bioactive calcium phosphate cements can be produced for bone regeneration through minimally invasive surgery., (Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

In this work gelatine was used as multifunctional additive to obtain injectable self-setting hydroxyapatite/gelatine composite foams for bone regeneration. The foaming and colloidal stabilization properties of gelatine are well known in food and pharmaceutical applications. Solid foams were obtained by foaming liquid gelatine solutions at 50 degrees C, followed by mixing them with a cement powder consisting of alpha tricalcium phosphate. Gelatine addition improved the cohesion and injectability of the cement paste. After setting the foamed paste transformed into a calcium deficient hydroxyapatite. The final porosity, pore interconnectivity and pore size were modulated by modifying the gelatine content in the liquid phase.

Future successes in regenerative medicine will depend on the development of new biodegradable biomaterials able to control tissue regeneration in vitro and in vivo. None of the products currently available to surgeons can combine all the essential characteristics for biodegradable biomaterials, which are tunable degradation rate, controlled inflammatory reaction, no toxicity and stimulation of tissue regeneration. These clinical features should be provided, together with ease of handling during surgery and cost-effective production. Here, an overview is presented of a novel class of soybean-based biomaterials, which can be manufactured as different hydrogel formulations, all tailored for specific clinical applications. ln vitro and in vivo studies have ascertained their activity on various biochemical and cellular components of regenerating tissues. Beyond their use, the ascertained bioactivity of some of the soybean components may open new investigations and commercial routes in regenerative medicine.

The reconstruction of large bone defects in periodontal, maxillofacial, and orthopedic surgery relies on the implantation of biomaterials able to support the growth of new tissue. None of the materials currently available is able to combine all the properties required, which are (i) easy handling, (ii) biodegradation, (iii) low immunogenicity, and more importantly, (iv) induction of tissue regeneration. A new class of biodegradable biomaterials has been obtained by simple thermosetting of defatted soybean curd. The final material can be processed into films, porous scaffolds, and granules for different surgical needs. When incubated in physiological solutions the material shows water uptake of 80%, elongation at break of 0.9 mm/mm, and 25% (w/w) degradation in 7 days. Soybean-based biomaterial granules are shown to reduce the activity of the monocytes/macrophages and of the osteoclasts and to induce osteoblast differentiation in vitro, thus demonstrating a bone regeneration potential suitable for many clinical applications.

The goal of this study was to characterize the protein composition of the conditioning film deposited onto the surface of ureteral stents during in vivo implantation and to relate its presence to the precipitation of calcium crystals. The protein pattern of the conditioning film of implanted nonencrusted and encrusted urological stents was assessed by SDS-PAGE and Western blot of the desorbed species. The results obtained highlighted different electrophoresis profiles between nonencrusted and encrusted stents. Western blot showed the ubiquitous presence of albumin, while Tamm-Horsfall Protein and alpha1-microglobulin adsorption was limited to nonencrusted devices. By an in vitro dynamic model in which artificial urine was flowed through the lumen of control and retrieved nonencrusted stents, we demonstrated that the organic layer remarkably enhanced crystal precipitation and aggregation events on the surface.

Bacterial adhesion to silver-coated orthopedic external fixation pins was compared with stainless steel controls in an in vitro study. Using five bacterial isolates from wound infections, the silver coating was found to reduce adhesion for Escherichia coli, Pseudomonas aeruginosa, and two strains of Staphylococcus aureus while the converse applied for Staphylococcus haemolyticus. When placed in human serum, both surfaces were conditioned to a similar extent with serum proteins; this conditioning lead to further reductions in bacterial adhesion, ultimately approaching similar levels for both stainless steel and silver-coated samples.

A recent study in our laboratory has identified the potential role of urine-derived alpha-1-microglobulin (alpha-1-m) in mediating Pseudomonas aeruginosa adhesion to polystyrene, while other workers have suggested a possible role of the protein in the immunological response. Due to the ubiquitous presence of alpha-1-m in body fluids, the adsorption of the protein from serum, cerebrospinal fluid, urine and used continuous ambulatory peritoneal dialysis fluid onto polystyrene was investigated. The treated surfaces were sequentially immersed in water and increasingly concentrated isopropanol-water solutions in order to selectively desorb bound proteins on the basis of their binding strength. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the wash supernatants showed different protein desorption profiles for each biological fluid, despite the qualitative similarity between the protein composition of the fluids, and highlighted the uptake of alpha-1-m from each fluid to the surface. In the case of urine, the analysis was extended to commercial polyurethane and silicone stents. The ease of desorption of urine-derived alpha-1-m could be correlated with surface hydrophobicity of the stent biomaterial.

Poly(2-hydroxyethylmethacrylate) [poly(HEMA)] is a widely used biomaterial which does not allow cell adhesion and growth on its surface, limiting its use in biomedical applications in which cell cohesion is detrimental. We have prepared a poly(HEMA)-gelatin composite hydrogel using a sequential interpenetrating polymer network technique. The properties of this material were compared with poly(HEMA) freeze-dried sponges in terms of morphology, mechanical properties and biocompatibility. Moreover, in vivo biocompatibility experiments highlighted the occurrence of cellular interactions on the surface of the poly(HEMA)-gelatin interpenetrating polymer network, which are usually absent when unmodified poly(HEMA) hydrogels are implanted in the same host organism. These tests also showed a progressive gelatin degradation from the surface to the bulk of the poly(HEMA)-gelatin specimens during short-term (7 d) implantation. Finally, in vitro tests confirmed an improved ability of this composite to scaffold for the cells.

According to the modern definition of biocompatibility, a biocompatible material need not be inert but be bioactive. A benign reactivity implies that the reactivity has to be appropriate for the intended use. Chitosan, a non-acetylated or partially deacetylated chitin (a linear homopolymer of beta (1-4)-linked N-acetylglucosamine) has been proposed as a biomaterial because of its apparent satisfactory biocompatibility. The present investigation demonstrates that chitosan has an in vitro stimulatory effect on both macrophage nitric oxide (NO) production and chemotaxis. The macrophage NO secretion is attributed to the N-acetylglucosamine unit of the chitosan molecule rather than to the glucosamine residue (28 and 15 microM NO respectively). Moreover, the immune stimulatory effect of chitosan was very specific since other glycosaminoglycans, such as N-acetyl-D-mannosamine and N-acetyl-D-galactosamine, had no effects on NO production (5 and 8 respectively). In vivo experiments strengthen this hypothesis. Transmission electron microscopy analysis identifies the presence of many leucocytes in the specimens after 14 d post-implantation, showing poor healing processes (i.e. fibroblast proliferation and collagen deposition) that characterize the tissue repair at this time in our animal model.