Biomedical subjects

J C Knowles

Publications and source records attributed to J C Knowles.

At least 19 recordsLinked to original sources

PubMed2007

Polylactic acid-phosphate glass composite foams as scaffolds for bone tissue engineering.

Phosphate glass (PG) of the composition 0.46(CaO)-0.04(Na(2)O)-0.5(P(2)O(5)) was used as filler in poly-L-lactic acid (PLA) foams developed as degradable scaffolds for bone tissue engineering. The effect of PG on PLA was assessed both in bulk and porous composite foams. Composites with various PG content (0, 5, 10, and 20 wt %) were melt-extruded, and either compression-molded or foamed through supercritical CO(2). Dynamic mechanical analysis on the bulk composites showed that incorporating 20 wt % PG resulted in a significant increase in storage modulus. Aging studies in deionized water in terms of weight loss, pH change, and ion release inferred that the degradation was due to PG dissolution, and dependent on the amount of glass in the composites. Foaming was only possible for composites containing 5 and 10 wt % PG, as an increase in PG increased the foam densities; however, the level of porosity was maintained above 75%. PLA-T(g) in the foams was higher than those obtained for the bulk. Compressive moduli showed no significant reinforcement with glass incorporation in either expansion direction, indicating no anisotropy. Biocompatibility showed that proliferation of human fetal bone cells was more rapid for PLA compared to PLA-PG foams. However, the proliferation rate of PLA-PG foams were similar to those obtained for foams of PLA with either hydroxyapatite or beta-tricalcium phosphate.

Biocompatible Materials↗

PubMed2006

Antimicrobial effect of silver-doped phosphate-based glasses.

In this study a range of phosphate-based glasses (PBG) doped with silver have been investigated for their antimicrobial activities. In disk diffusion assays, these compositions demonstrated microbistatic effects against a range of organisms including Staphylococcus aureus, Escherichia coli, Bacillus cereus, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and Candida albicans. The data obtained from the above studies allowed for an additional range of PBG containing lower amounts of silver to be studied for their effects on the growth and viability of S. aureus, E. coli, and C. albicans. PBG containing 3 and 5 mol % Ag were bactericidal for S. aureus and E. coli and significantly decreased the growth rate of C. albicans. A decrease in the dissolution rates of the glasses was seen with increasing Ag content over the range of concentrations investigated. Overall, 3 mol % Ag incorporated into the PBG investigated was sufficient to mount a potent antibacterial effect against the test organisms, and these compositions also gave excellent long-term release of Ag ions into the medium.

Anti-Bacterial Agents↗

PubMed2006

Electrospinning biomedical nanocomposite fibers of hydroxyapatite/poly(lactic acid) for bone regeneration.

Development of fibrous matrices of bioceramic-biopolymer nanocomposite offers great potential in the field of bone regeneration and tissue engineering. However, in order to produce electrospun fibers with homogeneous structure, it is essential for the ceramic powder to be fine and to remain stable in suspension. Herein, we developed a novel method whereby the bioceramic hydroxyapatite (HA) was kept in suspension in biopolymer poly(lactic acid) (PLA). The strategy was to introduce a surfactant hydroxysteric acid (HSA) between the hydrophilic HA powder and the hydrophobic chloroform-dissolved PLA. The HA nanopowder was dispersed effectively in HSA and mixed homogeneously with PLA. Continuous and uniform fibers were generated successfully with diameters of approximately 1-2 microm, and featured a well-developed nanocomposite structure of HA nanopowder-dispersed PLA. Initial cellular assays showed excellent cell attachment and proliferation and also enhanced expression of alkaline phosphatase at 7 days of culturing. The HA-PLA nanocomposite fibers may be potentially useful in tissue engineering applications, particularly as three-dimensional substrates for bone growth.

Bone Regeneration↗

PubMed2006

Investigation of silica-iron-phosphate glasses for tissue engineering.

Phosphate-based glasses have previously been examined for tissue engineering applications, however they degrade rapidly in solution reducing its pH to below 5. This study presents a series of phosphate-based glass compositions that degrade at a lower rate, allowing the pH to remain close to neutral in cell culture medium. The compositions investigated were P50Ca30Na(15-x)Fe5Si(x) where x = 0, 1, 3 and 5 mol%. The dissolution and effect on pH in distilled water and cell culture medium, and ion release in distilled water were investigated over 7 days and MG63 cell attachment to glass fibres was observed after 24 hrs. Dissolution was much slower in cell culture medium (3% mass loss) compared to distilled water (50% mass loss), due to the large quantity of ions and pH buffer present. After 7 days, in cell culture medium the pH remained between 7 and 8.5, however the pH in distilled water fell to between 4 and 3, with the final pH being lower the greater the SiO2 content. Increasing the SiO2 content of the glass resulted in an increase in dissolution rate whilst the pH was maintained at 7 in cell culture medium. The attachment and spreading of MG63 cells was observed on all compositions. These glass compositions may therefore be suitable for tissue engineering applications.

Biocompatible Materials↗

PubMed2005

Effect of iron on the surface, degradation and ion release properties of phosphate-based glass fibres.

Phosphate-based glass fibres (PGF) have the unique characteristic of being completely soluble in an aqueous environment, releasing bioactive and biocompatible ions. They have been proposed as tissue engineering scaffolds for craniofacial skeletal muscle regeneration, where myoblasts are seeded directly onto the fibres. Studies have shown that these cells have a preference in their initial attachment to fibres of certain composition and size, which in turn control the rate of degradation. This study investigated the relationship between the surface properties, degradation properties and ion release (cationic and anionic species) by altering the chemical composition of the PGF. Iron oxide (Fe2O3) was incorporated into glasses containing P2O5 (50 mol%), CaO (30 mol%) and Na2O (20 mol%). Six glass compositions with Fe2O3 ranging from 0 to 5 mol% by replacing the equivalent Na2O mol% were investigated. Contact angle measurements showed that polar interactions occurring on the glass surfaces diminished with increasing Fe2O3 content. This behaviour was reflected in the estimated surface energies of the glasses, where the overall surface energy decreased with increasing Fe2O3 content due to the decrease in polar or acid/base component. The incorporation of up to 5 mol% Fe2O3 into PGF resulted in a significant reduction in the degradation rate (by two orders of magnitude), which can be related to the formation of more hydration resistant P-O-Fe bonds. However, the degradation rate increased with decreasing fibre diameter (comparing average diameters of 31.6 +/- 6.5 microm versus 13.1 +/- 1.3 microm) for a given mass of fibre, and this is related to the surface area to volume ratio. Taken together the results suggest that fibres with the larger diameters and containing 3-5 mol% Fe2O3 could initially be a more durable scaffold than ones with 1 or 2 mol% Fe2O3 for initial cell attachment.

Absorbable Implants↗

PubMed2005

Soluble phosphate glass fibres for repair of bone-ligament interface.

Phosphate-based fibres of the generic composition (CaO)0.46-(Na2O)n-(Fe2O3)y-(P2O5)0.50 have been evaluated, in vitro, as three dimensional scaffolds for tissue engineering of the hard-soft tissue interface by assessing the fibre solubility and growth and functional gene expression of human cells. Primary human osteoblasts and fibroblasts were seeded onto scaffolds and maintained in culture for up to 21 days. Fluorescent immunolabeling revealed the spread cell morphology and significant proliferation pattern on these fibres, particularly on the 3 mol% Fe2O3-containing formulation. Real-time quantitative Polymerase Chain Reaction (rtQ-PCR) analysis of gene expression using TaqMan Probes was preformed and it has been established that committed cell differentiation was maintained by both cell types, and was strongly related to the 3 mol% Fe2O3 glass composition. These novel, readily manufactured, soluble glass fibres offer a biocompatible and biochemically favourable alternative in the search for suitable degradable materials used in Tissue Engineering.

Bone and Bones↗

PubMed2005

Cement from magnesium substituted hydroxyapatite.

Brushite cement may be used as a bone graft material and is more soluble than apatite in physiological conditions. Consequently it is considerably more resorbable in vivo than apatite forming cements. Brushite cement formation has previously been reported by our group following the mixture of nanocrystalline hydroxyapatite and phosphoric acid. In this study, brushite cement was formed from the reaction of nanocrystalline magnesium-substituted hydroxyapatite with phosphoric acid in an attempt to produce a magnesium substituted brushite cement. The presence of magnesium was shown to have a strong effect on cement composition and strength. Additionally the presence of magnesium in brushite cement was found to reduce the extent of brushite hydrolysis resulting in the formation of HA. By incorporating magnesium ions in the apatite reactant structure the concentration of magnesium ions in the liquid phase of the cement was controlled by the dissolution rate of the apatite. This approach may be used to supply other ions to cement systems during setting as a means to manipulate the clinical performance and characteristics of brushite cements.

Bone Cements↗

PubMed2005

Craniofacial muscle engineering using a 3-dimensional phosphate glass fibre construct.

The current technique to replace missing craniofacial skeletal muscle is the surgical transfer of local or free flaps. This is associated with donor site morbidity, possible tissue rejection and limited supply. The alternative is to engineer autologous skeletal muscle in vitro, which can then be re-implanted into the patient. A variety of biomaterials have been used to engineer skeletal muscle with limited success. This study investigated the use of phosphate-based glass fibres as a potential scaffold material for the in vitro engineering of craniofacial skeletal muscle. Human masseter (one of the muscles of mastication)--derived cell cultures were used to seed the glass fibres, which were arranged into various configurations. Growth factors and matrix components were to used to manipulate the in vitro environment. Outcome was determined with the aid of microscopy, time-lapse footage, immunofluorescence imaging and CyQUANT proliferation, creatine kinase and protein assays. A 3-dimensional mesh arrangement of the glass fibres was the best at encouraging cell attachment and proliferation. In addition, increasing the density of the seeded cells and using Matrigel and insulin-like growth factor I enhanced the formation of prototypic muscle fibres. In conclusion, phosphate-based glass fibres can support the in vitro engineering of human craniofacial muscle.

Biocompatible Materials↗

PubMed2005

Characterisation of antibacterial copper releasing degradable phosphate glass fibres.

Phosphate-based glass fibres (PGF) of the general formula Na(2)O-CaO-P(2)O(5) are degradable in an aqueous environment, and therefore can function as antibacterial delivery systems through the inclusion of ions such as copper. In this study, PGF with varying amounts of copper oxide (CuO) were developed for potential uses in wound healing applications. PGF with 0, 1, 5 and 10 mol% CuO were produced with different diameters and characterised in terms of structural and antibacterial properties. The effect of CuO and fibre pulling speed on the glass properties were investigated using rapid differential scanning calorimetry, differential thermal analysis and X-ray diffraction. The effect of two fibre diameters on short-term (3 h) attachment and killing against Staphylococcus epidermidis were investigated and were related to their rate of degradation in deionised water, as well as copper ion release measured using ion chromatography. Thermal analysis showed that there was a significant increase in the PGF glass transition temperature as the CuO content increased. There was a significant decrease in the rate of degradation with increasing CuO content and an increase in fibre diameter. Over 6 h, both the amount and rate of copper ions released increased with CuO content, as well as a reduction in fibre diameter thus increasing the surface area to volume ratio. There was a decrease in the number of viable staphylococci both attached to the CuO-containing fibres and in the surrounding environment.

Absorbable Implants↗

PubMed2005

Quantification of anion and cation release from a range of ternary phosphate-based glasses with fixed 45 mol% P2O5.

This article reports on the use of ion chromatography (IC) to investigate extensively the release profiles of both cations and anions and characterize the relationship between composition and degradation for a ternary-based Na(2)O-CaO-P(2)O(5) glass system developed as biomaterials. Studies are carried out on glasses with the formula 45P(2)O(5)-55(xCaO-Na(2)O) in deionized water, where x = 30, 35, and 40 mol%, using a cumulative release method, where the solution is changed at regular intervals. Degradation behavior is linear with time where the degradation rate shows an initial decrease with increasing CaO content. This rate then increases with a further addition of CaO. Cation release profiles follow similar trends to the degradation rates. Anion release profiles show a decrease for the PO(4) and linear polyphosphate (P(2)O(7) and P(3)O(10)) species with increasing CaO content. This decrease is attributed to the cross-linking of the Ca(2+) ions. In contrast, the cyclic P(3)O(9) anion exhibits the highest amount of anionic release, which demonstrates similar trends to the cations. These release patterns suggest that the cyclic P(3)O(9) species dominate the degradation rates. The proposed mode of degradation is a hydrolysis reaction, with the cyclic metaphosphate undergoing acid/base catalysis. The pH remains constant for the 30 and 35 mol% CaO glasses, and drops to about 5.5 for the 40 mol% composition. By using a response factor, it is possible to semiquantitatively analyze the additional peaks observed in the chromatograms. Suggestions are also put forward as to the identity of some of these unidentified peaks.

Absorbable Implants↗

PubMed2004

Processing, characterisation and biocompatibility of iron-phosphate glass fibres for tissue engineering.

Iron-phosphate glass fibres based on the CaO-Na2O-Fe2O3-P2O5 system have been processed and characterised via thermal, XRPD, dissolution rates, diameter and biocompatibility studies. The compositions investigated were fixed at 50mol% P2O5, and the CaO content was varied between 30, 35 and 40mol%. The Fe2O3 was added in low amounts from 1-5mol%, substituting it for the Na2O mol%. The number of Tc (crystallisation temperature) peaks detected from the thermal analysis traces only showed correlation with XRPD analysis, for five out of the 15 compositions investigated. It has been suggested that either the crystalline phases had very similar Tc temperatures or that the other phase(s) were present in very small quantities. There was a good match seen with number of Tm (melting temperature) peaks picked up from the DTA traces, with the number of phases identified from XRPD analysis. The main phases identified from XRPD were NaCa(PO3)3, CaP2O6 and NaFeP2O7. Using network connectivity (NC), predictions on Qn species present within the compositions investigated were made. The predicted species (metaphosphates) matched with phases identified from XRPD analysis. A decrease in dissolution rates for the bulk glass and glass fibres was seen with an increase in CaO mol%, along with an increase in Fe2O3 mol%. An increase in fibre dissolution rates was seen with a decrease in diameter size. The biocompatibility studies were conducted using a conditionally immortal muscle precursor cell line derived from the H-2Kb-tsA58 immortomouse. It was found that iron-phosphate glass fibres containing 4-5mol% Fe2O3 was sufficient for cell attachment and differentiation. It was seen that myotubes formed along the axis of the fibres (which was indicative of differentiation). The biocompatibility of these compositions was attributed to the enhanced chemical durability of the glass fibres.

Animals↗

PubMed2004

Phosphate glasses for tissue engineering: Part 1. Processing and characterisation of a ternary-based P2O5-CaO-Na2O glass system.

This paper presents the results of a study of the thermal properties, X-ray powder diffraction (XRPD), NMR and solubility of a range of phosphate-based glasses. Ion release and pH measurements were also obtained. The compositions were limited by fixing the P2O5 mol% content at 45, 50 and 55 mol%, and varying the CaO mol% at 30, 35 and 40 mol%. Initial data collected from thermal analysis showed an increase in the Tg values, with increasing CaO mol%, as expected. An increase in crystallisation temperatures with increasing CaO mol% was also observed, with sharp peaks indicating the presence of single and/or double phases. Initial XRPD data revealed that the 45 mol% P2O5 precipitated a calcium bridged trimetaphosphate (Na4Ca[PO3]6) at the sodium oxide contents of 25 and 20 mol%, but at the 15 mol% level two phases formed, NaCa[PO3]3 and Ca2P2O7. The 50 mol% P2O5 compositions showed two sodium phosphate-rich phases [NaCa(PO3)3 and NaPO3] for the lower calcium containing compositions, and a calcium phosphate phase [CaP2O6] for compositions with higher CaO mol%. The 55 mol% P2O5 compositions, exhibited similar phases for the lower calcium containing compositions, and a single calcium phosphate phase (CaP2O6) was identified for the higher calcium containing composition. NMR analysis revealed the presence of Q1 and Q2 species in the 45 mol% P2O5 compositions, and Q2 species present in the 50 and 55 mol% P2O5 compositions. The non-linear data obtained from the thermal and solubility analyses conducted were attributed to the packing density of the 45 mol% P2O5 compositions. The solubility was seen to decrease with increasing CaO mol%, for all the glasses investigated, and all the compositions showed a gradual decrease in pH with time, and this was accounted for by the release of Na+ and Ca2+ ions into solution.

Biocompatible Materials↗

PubMed2004

Phosphate glasses for tissue engineering: Part 2. Processing and characterisation of a ternary-based P2O5-CaO-Na2O glass fibre system.

This paper presents the results of a study of the thermal properties, solubility and dimensions of a range of phosphate-based glass fibres (PB-GFs). The glass compositions were limited by fixing the P2O5 content to 45, 50 and 55 mol%, and varying the CaO mol% at 30, 35 and 40. PB-GFs were obtained from the 50 and 55 mol% P2O5 compositions; however, we were unable to obtain fibres from the 45 mol% compositions. This was linked to the cross-linked density, network connectivity and average chain length of the compositions studied. With regards to thermal parameters investigated, initial data showed an increase of the Tg and crystallisation temperatures with increasing CaO mol% at each fixed phosphate content. A decrease in Tg temperatures was also observed with increasing P2O5 content to 55 mol%. The crystallisation temperatures obtained for compositions with fixed phosphate at 55 mol%, showed a reverse pattern, with a decrease in values as compared to the fixed 50 mol% phosphate compositions. The diameters of the fibres all decreased with increasing RPMs as expected, and the solubility also increased with increasing RPMs. This was related to the increased surface area of the higher RPM fibres. There was also a decrease seen in solubility with increasing CaO mol%.

Biocompatible Materials↗

PubMed2004

The effect of hot pressing on the physical properties of glass reinforced hydroxyapatite.

Hydroxyapatite (HA), being of physiological importance, can be developed synthetically for implant application. A number of avenues have been explored in order to improve the physical and biological properties of a variety of hydroxyapatite composites. However, the fact remains, hydroxyapatite lacks the mechanical properties needed to sustain high loads. This study investigates the advantages of hot pressing on the physical properties of HA and glass reinforced HA (GR-HA). The results show a significant enhancement in the mechanical properties of GR-HA composites compared to HA e.g. flexural bending strength values were given at 91.75 and 88.87 M Nm(-2) for GR-HA (CP15F) and GR-HA (CP20F) respectively, compared to 78.9 M Nm(-2) for HA. The results for other properties such as elastic modulus, fracture toughness, Vicker's hardness, density and porosity also demonstrate the benefit of adding phosphate based glasses as a sintering aid. This is supported by XRD analysis, highlighting the presence of a secondary phase (beta-TCP) in GR-HA systems and the positive effect it has on the physical properties. It must be brought to attention that densification of hot pressed HA and GR-HA composites is reached at a lower temperature compared to a previous study on the same materials that have undergone pressureless sintering.

Biocompatible Materials↗

PubMed2003

Effect of increasing silver content in phosphate-based glasses on biofilms of Streptococcus sanguis.

Silver is a powerful antibacterial ion that may be useful for dealing with localized infections, such as periodontitis. However, the use of silver in this role could be significantly improved by the development of an effective means of delivery. Phosphate-based glasses may provide a means of delivering the ions in a controlled manner. In our study, we have examined the effect of increasing silver content in phosphate-based glasses on biofilms of Streptococcus sanguis. Glasses of nominally the same dissolution rate were doped with silver at 1, 5,10, and 15 mol % and the number of colony-forming units (CFUs) determined after 6 and 24 h in a constant depth film fermenter (CDFF). The 1 mol % silver showed little change between 6 and 24 h. However, only 0.5 log CFUs were present on the glass containing 5 mol % at 6 h, and this reduced to virtually zero at 24 h. Few viable bacteria were found on the 10 mol % glass at both 6 and 24 h. The 15 mol % glass was investigated in this experiment, but no viable counts were detected. In a second set of experiments, glasses with 10 and 15 mol % silver were tested in the CDFF for up to 192 h. For the 10 mol % silver glass, there was approximately 0.8 log CFUs on this glass, which dropped to almost zero at 50 h. This was approximately 1.5-2.0 log reduction in CFUs compared to controls, and this difference was maintained for the first 50 h. After 50 h, there was a slow increase in the CFUs on all samples. However, CFUs on the 10 mol % silver glass were still suppressed up to 192 h compared to the controls. However, both controls also exhibited a decrease in viable counts at 50 h; this may have been due to carryover of silver into the control sample holders. However, this was minimized by the specimen layout in the CDFF and by having gaps between specimen sets. For the 15 mol % silver glass, counts for both this glass and the controls decreased to virtually zero between 24 and 48 h, but the numbers slowly increased up to 170 h, but the number of CFUs was suppressed compared to the 10 mol % glass at the same time point. The decrease seen is clearly the effect of the silver ions; however, the slow increase in CFUs may be accounted for by the biofilms forming thick layers on top of the glass discs inhibiting the release of ions from the glass by forming a "sacrificial layer" through which further ions have to diffuse.

Anti-Bacterial Agents↗

PubMed2003

The effect of increasing copper content in phosphate-based glasses on biofilms of Streptococcus sanguis.

This paper reports the effect of a series of phosphate-based glasses based on the Na(2)O-CaO-P(2)O(5) system doped with increasing amounts of copper and the effect of this increasing copper content on the viability of an in vitro biofilm of Streptococcus sanguis over an 8 day period in a constant depth film fermenter. The addition of copper to the glass caused the solubility to change, so the glasses were adjusted in order that their solubility in artificial saliva was nominally the same (0.3062 +/- 0.07 mg cm(-2) h(-1)). Initial experiments on glasses with 1.5% and 10% copper showed that after 6 h there was no statistical difference between the copper containing glasses and the non-copper containing glass and HA in terms of the viability of the biofilms. However, at 24 h there was an approximately 0.8-0.9 log reduction in viability of the biofilms grown on the 5% copper glass and an approximately 1.0-1.3 log reduction for the 10% copper containing glass. Further experiments on the glass with 10% copper and another glass with 15% copper were carried out in a time dependent study. For both glasses a clear decrease in viable counts at 24 h was found but for both glasses these returned to levels similar to those of controls. The initial decrease in viability during the first 24 h is likely to be due to the antibacterial effect of the copper and this could be correlated with copper content. The recovery after 24 h is probably due to the dead cells forming a barrier, making diffusion of the antibacterial ions, increasingly difficult. This study has shown that phosphate-based glasses could potentially be used to deliver antibacterial ions to help combat oral infections. Copper, which has been shown to have antibacterial properties, could be incorporated but some development of the glasses used in this investigation may be required. Further work is needed to determine the effectiveness of copper containing glasses on oral bacterial communities.

Anti-Bacterial Agents↗

PubMed2003

In vitro ageing of brushite calcium phosphate cement.

In vivo studies investigating the use of brushite cements have demonstrated mixed results with one or more of dissolution, hydrolysis, fragmentation and long term stability being demonstrated. It has been suggested that sample volume, implant location, and species can affect in vivo behaviour. As few in vitro studies on this cement system have been performed, this study aimed to compare the effects of static and dynamic in vitro ageing protocols on the phase composition, weight loss and mechanical properties of brushite cement. The effects of immersion liquid to cement volume ratio (LCVR) and sample volume on phase composition were investigated and comparative in vitro experiments were also performed in foetal bovine serum. It was determined that the weight loss after 28 days was up to seven times higher in serum than in phosphate buffered saline (PBS) and that fragmentation accounted for most of the weight loss observed. Hydroxyapatite was formed in PBS but not in serum when aged in refreshed media at all LCVRs investigated. This study has highlighted that LCVR, media refresh rate and media composition are critical to brushite cement performance. It appears that brushite cement removal from an implant site may be complex and dependent on physiological processes other than simple dissolution. A better understanding of these processes could provide the means to engineer more precise calcium phosphate cement degradation profiles.

Animals↗

PubMed2002

Effect of porosity reduction by compaction on compressive strength and microstructure of calcium phosphate cement.

Hydroxyapatite (HA) calcium phosphate cements (CPCs) are attractive materials for orthopedic applications because they can be molded into shape during implantation. However their low strength and brittle nature limits their potential applications to principally non-load-bearing applications. Little if any use has been made of the HA cement systems as manufacturing routes for preset HA bone grafts, which although not moldable pastes, are resorbable, unlike HA sintered ceramic. It is known that the strength of cements can be increased beyond that attainable from slurry systems by compaction, and this study investigates whether compaction significantly alters the specific surface area and pore-size distribution of CPC prepared according to the method of Brown and Chow. Compaction pressures of between 18 and 106 MPa were used to decrease the porosity from 50 to 31%, which resulted in an increase in the wet compressive strength from 4 to 37 MPa. The Weibull modulus was found to increase as porosity decreased; in addition the amount of porosity larger than the reactant particle size increased as porosity decreased. It is proposed that this was caused by a combination of voids created by the aqueous solvent used in fabrication and shrinkage that occurs on reaction. The specific surface area was unchanged by compaction.

Biocompatible Materials↗