Biomaterials (v.26, #21)

Calendar (I).

The adsorption of lysozyme and bovine serum albumin on silica and AlOOH-coated silica particles—representing negatively and positively charged oxide surfaces—was investigated. The protein-treated uncoated and completely AlOOH-coated silica particles were characterized by zeta potential analysis and UV/VIS spectroscopy. It was found that at pH 7 a protein oppositely charged to the oxide surface adsorbs in significantly higher amounts. In contrast, proteins of the same charge did not or only in very low amounts adsorbed on an oxide surface. As both oxide surfaces were measured to be very hydrophilic it can be concluded that electrostatic interactions dominate the adsorption process at the investigated experimental conditions. The pH regions where the proteins interact via attractive and repulsive coulomb interaction with the particular oxide surfaces were calculated and outlined.
Keywords: Protein adsorption; Surface charge; Silica; Alumina; Sol–gel;

Corrosion behaviour of cobalt–chromium dental alloys doped with precious metals by Lucien Reclaru; Heinz Lüthy; Pierre-Yves Eschler; Andreas Blatter; Christian Susz (4358-4365).
Precious metal based dental alloys generally exhibit a superior corrosion resistance, in particular enhanced resistance to pitting and crevice corrosion, compared to non-precious metal based alloys such as CoCr alloys. A new generation of Co–Cr alloys enriched with precious metals (Au, Pt, Ru) have now appeared on the market. The goal of this study was to clarify the effect of the precious metals additions on the corrosion behaviour of such alloys. Various commercial alloys with different doping levels were tested by electrochemical techniques in two different milieus based on the Fusayama artificial saliva and an electrolyte containing NaCl. Open circuit potentials, corrosion currents, polarization resistances, and crevices potentials were determined for the various alloys and completed by a coulometric analysis of the potentiodynamic curves. In addition, the microstructures were characterised by metallography and phase compositions analysed by EDX.The results show that the presence of precious metals can deteriorate the corrosion behaviour of Co–Cr alloys in a significant way. Gold doping, in particular, produces heterogeneous microstructures that are vulnerable to corrosive attack.
Keywords: Dental alloys; Co–Cr with precious metals; Gold; Platinum; Ruthenium; Corrosion; Crevice corrosion; Pitting corrosion; Metallography; Surface analysis;

Process and kinetics of bonelike apatite formation on sintered hydroxyapatite in a simulated body fluid by Hyun-Min Kim; Teruyuki Himeno; Tadashi Kokubo; Takashi Nakamura (4366-4373).
The surfaces of two hydroxyapatites (HA), which have been sintered at different temperatures of 800 and 1200 °C, was investigated as a function of soaking time in simulated body fluid (SBF) using transmission electron microscopy (TEM) attached with energy-dispersive spectrometry (EDX) and laser electrophoresis spectroscopy. The TEM–EDX indicated that after soaking in SBF, both the HAs form bonelike apatite by undergoing the same surface structural change, i.e., formations of a Ca-rich amorphous or nano-crystalline calcium phosphate (ACP) and a Ca-poor ACP, which eventually crystallized into bonelike apatite. Zeta potential characterized by the electrophoresis indicated that during exposure to SBF, the HA surfaces reveal negative surface charge, thereby interacting with the positive calcium ions in the fluid to form the Ca-rich ACP, which gains positive surface charge. The Ca-rich ACP on the HAs then interacts with the negative phosphate ions in the fluid to form the Ca-poor ACP, which stabilizes by being crystallized into bonelike apatite with a low solubility in the SBF. The exposure times for formations of these phases of the Ca-rich ACP, the Ca-poor ACP as well as the apatite were, however, all late on HA sintered at 1200 °C, compared with the HA sintered at 800 °C. This phenomenon was attributed to a lower initial negative surface charge of the HA sintered at 800 °C than of that one sintered at 1200 °C, owing to poverty in surface hydroxyl and phosphate groups which are responsible for the surface negativity of the HA. These indicate that sintered temperature of HA might influence not in terms of the process but in terms of the rate of formation of biologically active bonelike apatite on its surface, through which the HA integrates with living bone.
Keywords: Hydroxyapatite; Bioactivity; Apatite; Simulted body fluid (SBF); Surface potential;

The in vivo behaviour of a sol–gel glass and a glass-ceramic during critical diaphyseal bone defects healing by Jorge Gil-Albarova; Antonio J. Salinas; Antonio L. Bueno-Lozano; Jesus Román; Nicolo Aldini-Nicolo; Agustina García-Barea; Gianluca Giavaresi; Milena Fini; Roberto Giardino; Maria Vallet-Regí (4374-4382).
The in vivo evaluation, in New Zealand rabbits, of a sol–gel glass 70% CaO–30% SiO2 (in mol%) and a glass-ceramic obtained from thermal treatment of the glass, both bioactive in Kokubo's simulated body fluid (SBF), is presented. Femoral bone diaphyseal critical defects were filled with: (i) sol–gel glass cylinders, (ii) glass-ceramic cylinders, or (iii) no material (control group). Osteosynthesis was done by means of anterior screwed plates with an associate intramedullar Kirschner wire. Each group included 10 mature rabbits, 9 months old. Follow-up was 6 months. After sacrifice, macroscopic study showed healing of bone defects, with bone coating over the cylinders, but without evidence of satisfactory repair in control group. Radiographic study showed good implant stability and periosteal growth and bone remodelling around and over the filled bone defect. The morphometric study showed minimum evidences of degradation or resorption in glass-ceramic cylinders, maintaining its original shape, but sol–gel glass cylinders showed abundant fragmentation and surface resorption. An intimate union of the new-formed bone to both materials was observed. Mechanical study showed the higher results in the glass-ceramic group, whereas sol–gel glass and control group showed no differences. The minimum degradation of glass-ceramic cylinders suggests their application in critical bone defects locations of transmission forces or load bearing. The performance of sol–gel glass cylinders suggests their usefulness in locations where a quick resorption should be preferable, considering the possibility of serving as drug or cells vehicle for both of them.
Keywords: In vivo test; Bone healing; Bone substitutes; Bioactive glass and glass-ceramic; Osseointegration;

Biocompatibility and resorption of a brushite calcium phosphate cement by Felix Theiss; Detlef Apelt; Bastian Brand; Annette Kutter; Katalin Zlinszky; Marc Bohner; Sandro Matter; Christian Frei; Joerg A. Auer; Brigitte von Rechenberg (4383-4394).
A hydraulic calcium phosphate cement with β -tricalcium phosphate (TCP) granules embedded in a matrix of dicalcium phosphate dihydrate (DCPD) was implanted in experimentally created defects in sheep. One type of defect consisted of a drill hole in the medial femoral condyle. The other, partial metaphyseal defect was located in the proximal aspect of the tibia plateau and was stabilized using a 3.5 mm T-plate. The bone samples of 2 animals each per group were harvested after 2, 4, 6 and 8 weeks. Samples were evaluated for cement resorption and signs of immediate reaction, such as inflammation, caused by the cement setting in situ. Differences regarding these aspects were assessed for both types of defects using macroscopical, radiological, histological and histomorphometrical evaluations. In both defects the brushite matrix was resorbed faster than the β -TCP granules. The resorption front was followed directly by a front of new bone formation, in which residual β -TCP granules were embedded. Cement resorption occurred through (i) extracellular liquid dissolution with cement disintegration and particle formation, and (ii) phagocytosis of the cement particles through macrophages. Signs of inflammation or immunologic response leading to delayed new bone formation were not noticed at any time. Cement degradation and new bone formation occurred slightly faster in the femur defects.
Keywords: Biocompatibility; Resorption; Calcium phosphate; Cement; In vivo; Brushite;

Effect of fluoridation of hydroxyapatite in hydroxyapatite-polycaprolactone composites on osteoblast activity by Hae-Won Kim; Eun-Jung Lee; Hyoun-Ee Kim; Vehid Salih; Jonathan C. Knowles (4395-4404).
Fluorine was administered to a system of hydroxyapatite (HA)/polycaprolactone (PCL) ceramic-polymer bioactive composites for applications as hard tissue regeneratives. The HA was fluoridated at different levels (5%, 25%, 50% and 75%) in order to produce the fluor-hydroxyapatite (FHA)/PCL composites. The osteoblastic cellular responses to the composites were examined in terms of the cell attachment, proliferation and differentiation as well as the expression of bone-associated genes. The amount of fluorine released from the composites was controlled by changing the degree of fluoridation, and the cellular responses were strongly influenced by the level of fluoridation. The MG63 cells on the FHA-PCL attached and proliferated at a similar level to those on HA-PCL. However, the fluoridation of HA increased significantly the alkaline phosphatase (ALP) activity and osteocalcin (OC) production by the cells on the composites, which was measured by an enzymatic assay. Moreover, the gene expression level of ALP and OC in the cells was up regulated on the FHA-PCL, which was confirmed semi-quantitatively by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. These findings on the fluorine-administered biological composites (FHA-PCL) suggested that fluorine plays a significant role in stimulating the bone derived cellular activity, and the FHA-PCL composites have high potential for use as hard tissue regeneratives.
Keywords: Fluoridation; Fluor-hydroxyapatite (FHA); Poly( ε -caprolactone) (PCL); Hard tissue composites; Alkaline phosphatase activity; Osteocalcin;

In vitro cytotoxicity of nitric oxide-releasing sol–gel derived materials by Brian J. Nablo; Mark H. Schoenfisch (4405-4415).
The cytotoxicity of bare and PU-coated nitric oxide (NO)-releasing sol–gel derived materials (sol–gels) was investigated using L929 mouse fibroblasts in both direct and indirect contact models to differentiate between the biological impact of the sol–gel matrix and NO release. The flux of NO was varied up to 150 pmol cm−2  s−1 using N-(6-aminohexyl)-aminopropyltrimethoxysilane (balance iso-butyltrimethoxysilane) diazeniumdiolate (NO donor)-modified sol–gels. The addition of a polyurethane (PU) outer membrane greatly improved the stability of the sol–gel matrix without significantly suppressing the NO flux. Direct contact studies demonstrated a cytotoxic effect that was dependent on the aminosilane content of the sol–gel. The use of the thin PU overcoat eliminated this effect. A direct cytotoxicity dependence of NO release for L929 fibroblasts was discovered from indirect contact studies, where 24 h exposure to NO fluxes in excess of 50 pmol cm−2  s−1 was cytotoxic.
Keywords: Nitric oxide; Sol–gel; Controlled release; Fibroblasts; Biocompatibility;

Induction of protein oxidation by cobalt and chromium ions in human U937 macrophages by Alain Petit; Fackson Mwale; Cathy Tkaczyk; John Antoniou; David J. Zukor; Olga L. Huk (4416-4422).
Metal particles and ions from hip prostheses have the potential to induce the production of reactive oxygen species (ROS), making them prime suspects for disturbing the cellular balance of oxidants/antioxidants (redox state of the cell). To better understand the cellular effect of metal ions from metal-on-metal prostheses, the aim of this study was to examine the effect of cobalt (Co2+) and chromium (Cr3+) ions on protein oxidation in human U937 macrophages. Protein oxidation was measured by Western blot using antibodies directed against dinitrophenylhydrazine (DNP)-derivatized protein carbonyls, the most commonly measured products of protein oxidation in biological samples. Three DNP-derived proteins were detected. The first has a molecular weight of 16 kDa and is expressed at a very low level. The second has a molecular weight of 48 kDa and its level is not regulated by metal ions. The third is a 69 kDa protein and its level is regulated by Co2+ and Cr3+ ions. Therefore, the last band served as a marker of protein oxidation in the present study. Results showed that Co2+ and Cr3+ ions induced a time- and dose-dependent protein oxidation reaching 6.5 and 2.9 times the control after 72 h, respectively, which were inhibited by the antioxidant glutathione monoethyl-ester. Finally, results showed that the oxidized proteins are mainly found in the cytoplasmic fraction of the cells and are absent from the nucleus. In conclusion, our results suggest that metal ions from metal-on-metal prostheses have the potential to modify the redox state of cells both locally (periprosthetic environment) or systematically (circulating cells). The long term effect of these ions on protein oxidation in vivo remains to be investigated.
Keywords: Hip replacement; Metal ions; Oxidation; Protein; Macrophage; Cytotoxicity;

Hydrophobicity as a design criterion for polymer scaffolds in bone tissue engineering by Edwin J.P. Jansen; Raymond E.J. Sladek; Hila Bahar; Avinoam Yaffe; Marion J. Gijbels; Roel Kuijer; Sjoerd K. Bulstra; Nick A. Guldemond; Itzhak Binderman; Leo H. Koole (4423-4431).
Porous polymeric scaffolds play a key role in most tissue-engineering strategies. A series of non-degrading porous scaffolds was prepared, based on bulk-copolymerisation of 1-vinyl-2-pyrrolidinone (NVP) and n-butyl methacrylate (BMA), followed by a particulate-leaching step to generate porosity. Biocompatibility of these scaffolds was evaluated in vitro and in vivo. Furthermore, the scaffold materials were studied using the so-called demineralised bone matrix (DBM) as an evaluation system in vivo. The DBM, which is essentially a part of a rat femoral bone after processing with mineral acid, provides a suitable environment for ectopic bone formation, provided that the cavity of the DBM is filled with bone marrow prior to subcutaneous implantation in the thoracic region of rats. Various scaffold materials, differing with respect to composition and, hence, hydrophilicity, were introduced into the centre of DBMs. The ends were closed with rat bone marrow, and ectopic bone formation was monitored after 4, 6, and 8 weeks, both through X-ray microradiography and histology. The 50:50 scaffold particles were found to readily accommodate formation of bone tissue within their pores, whereas this was much less the case for the more hydrophilic 70:30 counterpart scaffolds. New healthy bone tissue was encountered inside the pores of the 50:50 scaffold material, not only at the periphery of the constructs but also in the center. Active osteoblast cells were found at the bone-biomaterial interfaces. These data indicate that the hydrophobicity of the biomaterial is, most likely, an important design criterion for polymeric scaffolds which should promote the healing of bone defects. Furthermore, it is argued that stable, non-degrading porous biomaterials, like those used in this study, provide an important tool to expand our comprehension of the role of biomaterials in scaffold-based tissue engineering approaches.
Keywords: Tissue engineering; Scaffolds; Biocompatibility in vivo; Demineralised bone matrix;

Biotransformation and liver-specific functions of human hepatocytes in culture on RGD-immobilized plasma-processed membranes by Loredana De Bartolo; Sabrina Morelli; Linda C. Lopez; Lidietta Giorno; Carla Campana; Simona Salerno; Maria Rende; Pietro Favia; Loredana Detomaso; Roberto Gristina; Riccardo d’Agostino; Enrico Drioli (4432-4441).
In this paper we report on the metabolic response of human hepatocytes grown on polyethersulfone membranes surface modified with a plasma-deposited acrylic acid coating and RGD peptide covalently immobilized through a “spacer arm” molecule. The modified surfaces were characterized by means of X-ray photoelectron spectroscopy and water contact angle measurements.The performance of modified and unmodified membranes was evaluated by assessing the expression of liver specific and biotransformation functions of human hepatocytes. Diclofenac, a non-steroidal anti-inflammatory drug, was used to investigate the biotransformation functions.Surface-modified membranes elicit specific cellular responses and induce hepatocytes to enhance the synthesis rate of albumin and urea, particularly in the presence of diclofenac. Also the biotransformation functions were expressed at high levels.
Keywords: Membrane; Plasma modification; RGD immobilization; Human hepatocytes; Liver-specific functions; Drug biotransformation;

Influence of macroporous protein scaffolds on bone tissue engineering from bone marrow stem cells by Hyeon Joo Kim; Ung-Jin Kim; Gordana Vunjak-Novakovic; Byoung-Hyun Min; David L. Kaplan (4442-4452).
The aim of this study was to investigate the effect of three-dimensional silk fibroin scaffold preparation methods (aqueous and solvent) on osteogenic responses by human bone marrow stem cells (hMSCs). Macroporous 3D protein scaffolds with similar sized pores of 900±50 μm were prepared either by an organic solvent process (hexafluoro-2-propanol, HFIP) or an aqueous process. hMSCs were expanded, seeded on the scaffolds, and cultured up to 28 days under static conditions in osteogenic media. hMSCs seeded onto the water-based silk scaffolds showed a significant increase in cell numbers (p<0.01) vs. the HFIP-prepared silk scaffolds. Significantly higher (p<0.01) alkaline phosphatase (ALPase) activity and calcium deposition were apparent after 28 days of culture in the water-based silk scaffolds when compared to the HFIP-derived silk scaffolds. Transcript levels for collagen type I (Col I), ALP, and osteopontin (OP) increased (p<0.05) in the water-based silk scaffolds in comparison to the HFIP-derived materials. At early stages of culture, increased expression of OP and collagen type II (Col II) were also observed in both scaffolds. Expression of Col II, MMP 13, Col I, and OP proteins increased in the water-based silk scaffolds in comparison to the HFIP-derived scaffolds while bone sialoprotein (BSP) proteins increased in the HFIP-derived silk scaffolds in comparison to the water-based scaffolds after 28 days of culture. Histological analysis showed the development of bone-like trabeculae with cuboid cells in an extracellular matrix (ECM) in the water-based silk scaffolds with more organization than in the HFIP-derived material after 28 days of culture. Alcian blue staining demonstrated the presence of proteoglycan in the ECM formed in the water-based scaffolds but not in the HFIP-prepared silk scaffolds. The results suggest that macroporous 3D aqueous-derived silk fibroin scaffolds provide improved bone-related outcomes in comparison to the HFIP-derived systems. These data illustrate the importance of materials processing on biological outcomes, as the same protein, silk fibroin, was used in both preparations.
Keywords: Silk; Fibroin; Bone; Stem cells; Tissue engineering; Scaffolds;

Adhesion and proliferation of OCT-1 osteoblast-like cells on micro- and nano-scale topography structured poly(l-lactide) by Yuqing Wan; Yong Wang; Zhimin Liu; Xue Qu; Buxing Han; Jianzhong Bei; Shenguo Wang (4453-4459).
The impact of the surface topography of polylactone-type polymer on cell adhesion was to be concerned because the micro-scale texture of a surface can provide a significant effect on the adhesion behavior of cells on the surface. Especially for the application of tissue engineering scaffold, the pore size could have an influence on cell in-growth and subsequent proliferation. Micro-fabrication technology was used to generate specific topography to investigate the relationship between the cells and surface. In this study the pits-patterned surfaces of polystyrene (PS) film with diameters 2.2 and 0.45 μm were prepared by phase-separation, and the corresponding scale islands-patterned PLLA surface was prepared by a molding technique using the pits-patterned PS as a template. The adhesion and proliferation behavior of OCT-1 osteoblast-like cells morphology on the pits- and islands-patterned surface were characterized by SEM observation, cell attachment efficiency measurement and MTT assay. The results showed that the cell adhesion could be enhanced on PLLA and PS surface with nano-scale and micro-scale roughness compared to the smooth surfaces of the PLLA and PS. The OCT-1 osteoblast-like cells could grow along the surface with two different size islands of PLLA and grow inside the micro-scale pits of the PS. However, the proliferation of cells on the micro- and nano-scale patterned surface has not been enhanced compared with the controlled smooth surface.
Keywords: Poly(l-lactide); Polystyrene; Cell adhesion; Topography structure; Osteoblast; Micro-scale; Nano-scale;

When surface-reactive (bioactive) coatings are applied to medical implants by means of CO2 laser processing, the bioactivity of the surface of the implant can be locally modified to match the properties of the surrounding tissues to provide a firm fixation of the implant. The aim of this study was to compare the heat treated TiO2 coatings with the laser-treated TiO2 coatings in terms of amorphous-crystalline-phase development. The coatings were characterized with thin-film X-ray diffraction (TF-XRD), atomic force microscopy (AFM) and scanning electron microscopy (SEM). The TiO2 coatings heat treated at 500 °C known to be bioactive in SBF (simulated body fluid) consisted mainly of anatase with some rutile-phase, suggesting a predominant effect of anatase on reactivity of coatings. However, the coatings preheat-treated at 500 °C with further laser treatment exhibited enhanced bioactivity while consisting mainly of rutile. These findings indicated a key role of both rutile and anatase for the reactivity of the coatings. Without preheat treatment, by laser treatment alone, the amorphous titania coatings developed into mixed anatase/rutile containing coatings. This structural organization and the increase in crystal size are thus considered to be the reasons for their bioactivity. The SBF results indicate the possibility to control bioactivity by altering laser power used through the anatase/rutile crystallinity enhancement.
Keywords: Titanium oxide; Crystallinity; Laser; Bioactivity; In vitro; Bioactive; Coatings; CO2 Laser;

Biomechanical properties of high-toughness double network hydrogels by Kazunori Yasuda; Jian Ping Gong; Yoshinori Katsuyama; Atsushi Nakayama; Yoshie Tanabe; Eiji Kondo; Masaru Ueno; Yoshihito Osada (4468-4475).
This study evaluated the wear property of four novel double-network (DN) hydrogels, which was composed of two kinds of hydrophilic polymers, using pin-on-flat wear testing. The gels involve PAMPS–PAAm gel which consists of poly(2-acrylamide-2-metyl-propane sulfonic acid) and polyacrylamide, PAMPS–PDAAAm gel which consists of poly(2-acrylamide-2-metyl-propane sulfonic acid) and poly(N,N′-dimetyl acrylamide), Cellulose/PDMAAm gel which consists of bacterial Cellulose and poly dimetyl-acrylamide, and Cellulose–Gelatin gel which consists of bacterial Cellulose and Gelatin. Ultra-high molecular weight polyethylene (UHMWPE) was used as a control of a clinically available material. Using a reciprocating apparatus, 106 cycles of friction between a flat specimen and ceramic pin were repeated in water under a contact pressure of 0.1 MPa. To determine the depth and the roughness of the concave lesion created by wear, a confocal laser microscope was used. As a result, the maximum wear depth of the PAMPS–PDMAAm gel (3.20 μm) was minimal in the five materials, while there was no significant difference compared to UHMWPE. There were significant differences between UHMWPE and one of the other three gels. The PAMPS–PAAm gel (9.50 μm), the Cellulose–PDMAAm gel (7.80 μm), and the Cellulose–Gelatin gel (1302.40 μm). This study demonstrated that the PAMPS–PDMAAm DN gel has an amazing wear property as a hydrogel that is comparable to the UHMWPE. In addition, the PAMPS–PAAm and Cellulose–PDMAAm DN gels are also resistant to wear to greater degrees than conventionally reported hydrogels. On the other hand, this study showed that the Cellulose–Gelatin DN gel was not resistant to wear.
Keywords: Double network hydrogel; Wear property; Pin-on-flat test; Artificial cartilage;

In vitro study of anticancer drug doxorubicin in PLGA-based microparticles by Rongyi Lin; Lian Shi Ng; Chi-Hwa Wang (4476-4485).
Doxorubicin (DOX), also known as adriamycin, is an anthracycline drug commonly used in cancer chemotherapy. Unfortunately, its therapeutic potential has been restricted by its dose limited cardiotoxicity and the resistance developed by the tumor cells to the molecule after some time of treatment. One way to overcome these problems is to encapsulate the drug in poly (d, l-lactide-co-glycolide) (PLGA) microparticles. This paper investigates the release characteristics of DOX from polymeric carriers fabricated using the spray-drying technique. The encapsulation efficiency, size and morphology of the various polymeric devices were also determined. In order to improve the release characteristics, Pluronic P105 (PLU) and poly (l-Lactide) (PLLA) are individually used in combination with PLGA. Finally, a cytotoxicity test was performed using Glioma C6 cancer cells to investigate the cytotoxicity of DOX delivered from PLGA microparticles. It has been found that the cytotoxicity of DOX to Glioma C6 cancer cells is enhanced when DOX is delivered from PLGA polymeric carrier.
Keywords: Microparticles; Doxorubicin (DOX); Poly(d,l-lactide-co-glycolide) (PLGA); Cytotoxicity; Spray-drying;

Calcium polyphosphate antibiotic delivery matrices were prepared using a unique processing technique involving the exposure of calcium polyphosphate pastes to high humidity for 0, 5, 24 or 48 h to induce gelling. Subsequently, samples were dried for a minimum of 24 h. The mild conditions associated with matrix fabrication readily allowed for vancomycin incorporation within an environment that did not disrupt antibiotic activity. While reproducible from a processing standpoint, the gelling and drying process did contribute to a decrease in matrix tensile strength and the formation of significant pores near the surface of the matrices. Generally, the core of the gelled matrices appeared to be denser than their non-gelled counterparts. The degree of phosphate chain lysis during the gelling and drying stages was quantified using solution 31P nuclear magnetic resonance (NMR) spectroscopy. Both NMR and Raman spectroscopy indicated that the presence of vancomycin did not appreciably alter the matrix formation process. The ability to incorporate clinically relevant levels of antibiotic within this degradable bone substitute matrix suggests the potential of this approach for creating a localized antibiotic delivery system to treat osteomyelitis infections.
Keywords: Calcium phosphate; Drug delivery; Degradation; Bone repair;