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Takabuti, was a female who lived in ancient Egypt during the 25th Dynasty, c.660 BCE. Her mummified remains were brought to Belfast, Northern Ireland, in 1834 and are currently displayed in the Ulster Museum. To gain insight into Takabuti’s ancestry, we used deep sampling of vertebral bone, under X-ray control, to obtain non-contaminated bone tissue from which we extracted ancient DNA (aDNA) using established protocols. We targeted the maternally inherited mitochondrial DNA (mtDNA), known to be highly informative for human ancestry, and identified 38 single nucleotide variants using next generation sequencing. The specific combination of these SNVs suggests that Takabuti belonged to mitochondrial haplogroup H4a1. Neither H4 nor H4a1 have been reported in ancient Egyptian samples, prior to this study. The modern distribution of H4a1 is rare and sporadic and has been identified in areas including the Canary Islands, southern Iberia and the Lebanon. H4a1 has also been reported in ancient samples from Bell Beaker and Unetice contexts in Germany, as well as Bronze Age Bulgaria. We believe that this is an important finding because first, it adds to the depth of knowledge about the distribution of the H4a1 haplogroup in existing mtDNA, thus creating a baseline for future occurrences of this haplogroup in ancient Egyptian remains. Second, it is of great importance for archaeological sciences, since a predominantly European haplogroup has been identified in an Egyptian individual in Southern Egypt, prior to the Roman and Greek influx (332BCE).

An important challenge for colloid scientists is to design injectable dispersions that provide structural support for damaged soft tissue and enable regeneration of tissue over the longer term. In this article we highlight a new area of research that aims to produce pH-responsive microgel dispersions that restore the mechanical properties of damaged, load-bearing, soft tissue. Chronic back pain due to degeneration of the intervertebral disc (IVD) is a major health problem and is the primary potential application for the work discussed. pH-Responsive microgel dispersions contain cross-linked polymer particles that swell when the pH approaches the pKa of the incorporated ionic co-monomer. The work considered here involves microgel particles containing MAA (methacrylic acid). The particles show pronounced pH-triggered swelling. The concentrated microgel dispersions change from a fluid to a gel at pH values greater than ca. 6.2, which is within the physiological pH range. The rheological properties are pH-dependent and can be adjusted using particle composition or concentration. Degenerated IVDs containing injected, gelled, microgel dispersions show improved mechanical properties. The disc height under biomechanically meaningful loads can be restored to values observed in non-degenerated IVDs. We also discuss the steps required to provide a minimally invasive injectable microgel system for restoring both the IVD mechanical properties and regenerating tissue in vivo. The approach discussed should also be suitable for other soft tissue types in the body.

Gels that feature high internal porosity and have both high elasticity and ductility have potential to provide immediate load support and enable subsequent tissue regeneration of damaged soft tissue if combined with cells. Herein, we report results from a recent investigation of novel poly(methyl methacrylate-co-methacrylic acid), (PMMA-MAA) and poly(ethyl acrylate-co-methacrylic acid), (PEA-MAA) biodegradable, pH-sensitive particle gels which are with high porosity, elasticity and ductility. These gels formed at physiological pH range and are potentially injectable. The particles were prepared using solvent evaporation. They were functionalized by crosslinking the MAA groups of the particles via bis-amide formation with either cystamine (CYS) or 3,3′-dithiodipropionic acid dihydrazide (DTP) which simultaneously incorporated reversibility due to the presence of disulphide bonds within the crosslinker. The crosslinked particles were observed by dynamic light scattering to swell appreciably in size upon increasing the pH. Concentrated dispersions formed elastic and ductile physical gels within the physiological pH range. A key finding of this study was that for crosslinked particles of similar composition the formation of considerably more elastic and ductile gels was observed from the most lightly crosslinked particles. Furthermore, compared to the PMMA-MAA/CYS and PEA-MAA/CYS gels, those formed from DTP-crosslinked particles had higher elasticity, thicker pore walls and improved interconnectivity. For the PMMA-MAA/DTP gels an elastic modulus value as high as 100 kPa and a yield strain greater than 100% were observed for a gel containing only 5 wt% of particles. The improved mechanical properties of these new gel-forming dispersions imply that they now have good potential for future application as injectable gels for regenerative medicine.

Surface tumours of bone may be a cause of confusion and diagnostic difficulty. Confusion may arise from the several descriptive adjectives used – parosteal, periosteal and juxtacortical. Diagnostic difficulties may arise from the lack of awareness of less common entities, insufficient biopsy sampling and a failure to understand the precise relationship of a lesion and the bone surface. In this review we define and classify the important lesions and indicate imaging, macroscopic and microscopic features which are useful for diagnosis.

This review aims to provide a summary of current concepts of ageing in relation to the musculoskeletal system, highlighting recent advances in the understanding of the mechanisms involved in the development of age-related changes in bone, skeletal muscle, chondroid and fibrous tissues. The key components of the musculoskeletal system and their functions are introduced together with a general overview of the molecular hallmarks of ageing. A brief description of the normal architecture of each of these tissue types is followed by a summary of established and developing concepts of mechanisms contributing to the age-related alterations in each. Extensive detailed description of these changes is beyond the scope of this review; instead, we aim to highlight some of the most significant processes and, where possible, the molecular changes underlying these and refer the reader to in-depth, subspecialist reviews of the individual components for further details.

Polymer dots (PDs) are promising fluorescent probes for biomaterials applications. Here, novel cytocompatible composite PD particles have been synthesised with a core–shell–shell morphology. The particles show near-infrared emission, improved fluorescent brightness and enhanced colloidal stability compared to pure PDs. The particles also show non-radiative resonance energy transfer (NRET) with a model dye.

Conductive gel composites are attracting considerable attention because of their interesting electrical and mechanical properties. Here, we report conductive gel composites constructed using only colloidal particles as building blocks. The composites were prepared from mixed dispersions of vinyl-functionalised pH-responsive microgel particles (MGs) and multi-walled carbon nanotubes (CNTs). MGs are crosslinked pH-responsive polymer colloid particles that swell when the pH approaches the pKa of the particles. Two MG systems were used which contained ethyl acrylate (EA) or methyl acrylate (MA) and around 30 mol% of methacrylic acid (MAA). The MA-based MG is a new pH-responsive system. The mixed MG/CNT dispersions formed thixotropic physical gels. Those gels were transformed into covalent interlinked electrically conducting doubly crosslinked microgel/CNT composites (DX MG/CNT) by free-radical reaction. The MGs provided the dual roles of dispersant for the CNTs and macro-crosslinker for the composite. TEM data showed evidence for strong attraction between the MG and the CNTs which facilitated CNT dispersion. An SEM study confirmed CNT dispersion throughout the composites. The mechanical properties of the composites were studied using dynamic rheology and uniaxial compression measurements. Surprisingly, both the ductility and the modulus of the gel composites increased with increasing CNT concentration used for their preparation. Human adipose-derived mesenchymal stem cells (AD-MSCs) exposed to DX MG/CNT maintained over 99% viability with metabolic activity retained over 7 days, which indicated non-cytotoxicity. The results of this study suggest that our approach could be used to prepare other DX MG/CNT gel composites and that these materials may lead to future injectable gels for advanced soft-tissue repair.

Biodegradable pH-responsive hollow polymer particles offer excellent potential for preparing high performance biomaterials. Unfortunately, the established methods for pH-responsive hollow particle preparation are laborious and difficult to scale up. Recently, we reported that pH-responsive hollow particles could be prepared using solvent evaporation [Bird et al., Chem. Commun., 2011, 47, 1443]. Here, we greatly expand and extend that work by investigating four new pH-responsive hollow particle systems based on poly(MMA-co-MAA) (methyl methacrylate and methacrylic acid) and poly(EA-co-MAA) (EA is ethyl acrylate). The hollow polymer particles were crosslinked with cystamine after preparation to give redox sensitive, biodegradable, hollow particles. For one of the systems a remarkable particle-in-hollow particle morphology was observed. The pH-triggered swelling of the hollow particles was studied and pH-triggered release of a model solute from these new hollow particles was demonstrated. The dispersions formed physical gels in the physiological pH range. The hollow particle physical gels had elastic modulus values as high as 4000 Pa at low total polymer concentrations. The swelling properties of the particles and the mechanical properties of the gels were tuneable using copolymer composition. The particles and gels could be disassembled with glutathione. The properties of these new gel-forming dispersions imply they have good potential for future application as injectable gels for regenerative medicine. © 2012 The Royal Society of Chemistry.

Immunohistochemistry is an important tool in the investigation of ancient mummified remains because of its ability not only to detect proteins but also to isolate their location to specific tissues and thereby improve confidence that the results are genuine. A mouse model of Egyptian mummification has been used to demonstrate that the survival of proteins, judged by the retention of immunohistochemical staining, varies markedly. Some survive the process well, whereas others become barely detectable despite the morphology of the tissue being excellently preserved. The results obtained show that protein preservation is multi-factorial, with tissue type and degradation, and the properties of the protein itself all having significant effects. Proteins forming large, multi-subunit complexes such as collagen IV appear to be more resistant to degradation than those that do not, such as S-100. Although modern modelling studies cannot replicate the full extent of degradative processes and taphonomic changes experienced by real mummies, the results obtained can be useful for guiding research that requires ancient tissues.

pH-responsive microgels are crosslinked polymer colloids that swell when the pH approaches the pK a of the particles. They have potential application for injectable gels for tissue repair and drug delivery systems. This study focuses on the pH-triggered gelation behaviour of a series of poly (EA/MAA/X) microgels. EA and MAA are ethylacrylate and methacrylic acid. Here, we investigate the effect of crosslinking monomer type (X) on microgel properties. The crosslinking monomers used were poly (ethyleneglycol) dimethacrylate (PEGD), ethyleneglycol dimethacrylate (EGD) and butanediol diacrylate (BDD). The microgel containing PEGD (m-PEGD) is a new system. The microgel containing BDD (m-BDD) was used as a control system. The concentrated microgel dispersions formed physical gels when the pH was increased to 5.3–6.7, and the polymer volume fractions (ϕ p ) were above about 0.05. Evidence from photon correlation spectroscopy (PCS) and dynamic rheology was presented for abrupt pH-triggered increases, and then decreases of the hydrodynamic diameters for m-PEGD and the microgel prepared using EGD (m-EGD). This appears to be tuneable through crosslinker structure. An unexpected gelation behaviour, which may involve a new gel state for microgels, was found for m-PEGD dispersions. Uniquely, those dispersions formed gels at pH values less than the microgel's pK a . This behaviour was linked to an outer-shell electrostatic repulsive interaction. The data point to a phenomenon, whereby the m-PEGD shells appear to explode at pH values above 7.0. The control microgel prepared, using BDD (m-BDD), did not show any evidence of shell fragmentation at any pH. That microgel has potential as a model pH-responsive microgel system in that the properties measured by PCS and rheology agreed well. To probe that system in more detail, the rheological data for m-BDD was analysed using scaling theory. The variation of the storage modulus (G') with ϕ p gave a scaling exponent of 2.0.

pH-responsive microgels are cross-linked polymer colloids that swell when the pH approaches the pK a of the particles. In this work, we present a comprehensive investigation of pH-triggered particle swelling and gel formation for a range of microgels containing methacrylic acid (MAA). The microgels investigated have the general composition poly(A/MAA/X), where A and X are the primary co-monomer and cross-linking monomer, respectively. The primary co-monomers were methyl methacrylate (MMA), ethyl acrylate (EA) or butyl methacrylate. The cross-linking monomers were either butanediol diacrylate (BDDA) or ethyleneglycol dimethacrylate (EGDMA). The microgels were studied using scanning electron microscopy, photon correlation spectroscopy (PCS) and dynamic rheology measurements. Gel phase diagrams were also constructed. The particles swelled significantly at pH values greater than approximately 6.0. It was shown that poly(EA/MAA/X) microgels swelled more strongly than poly(MMA/MAA/X) microgels. Furthermore, greater swelling occurred for particles prepared using EGDMA than BDDA. Concentrated dispersions of all the microgels studied exhibited pH-triggered gel formation. It was found that the fluid-to-gel transitions for the majority of the six microgel dispersions investigated could be explained using PCS data. In those cases, gelation was attributed to a colloidal glass transition. Interestingly, the microgels that were considered to have the highest hydrophobic content gelation occurred under conditions where little particle swelling was evident from PCS. The data presented show that gelled poly(EA/MAA/BDDA) and poly(MMA/MAA/EGDMA) microgel dispersions have the strongest elasticities at pH = 7.

The potential of various pH-responsive alkyl (meth)acrylate ester- and (meth)acrylic acid-based copolymers, including poly(methyl methacrylate-co-acrylic acid) (PMMA-AA) and poly(n-butyl acrylate-co-methacrylic acid) (PBA-MAA), to form pH-sensitive biocompatible and biodegradable hollow particle gel scaffolds for use in non-load-bearing soft tissue regeneration have been explored. The optimal copolymer design criteria for preparation of these materials have been established. Physical gels which are both pH- and redox-sensitive were formed only from PMMA-AA copolymers. MMA is the optimal hydrophobic monomer, whereas the use of various COOH-containing monomers, e.g., MAA and AA, will always induce a pH-triggered physical gelation. The PMMA-AA gels were prepared at physiological pH range from concentrated dispersions of swollen, hollow, polymer-based particles cross-linked with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP). A linear relationship between particle swelling ratios, gel elasticity, and ductility was observed. The PMMA-AA gels with lower AA contents feature lower swelling ratios, mechanical strengths, and ductilities. Increasing the swelling ratio (e.g., through increasing AA content) decreased the intraparticle elasticity; however, intershell contact and gel elasticity were found to increase. The mechanical properties and performance of the gels were tuneable upon varying the copolymers' compositions and the structure of the cross-linker. Compared to PMMA-AA/CYS, the PMMA-AA/DTP gels were more elastic and ductile. The biodegradability and cytotoxicity of the new hollow particle gels were tested for the first time and related to their composition, mechanical properties, and morphology. The new PMMA-AA/CYS and PMMA-AA/DTP gels have shown good biocompatibility, biodegradability, strength, and interconnected porosity and therefore have good potential as a tissue repair agent.

Recent advances in surgical techniques have made it possible to study the changes that are known as degeneration of the intervertebral disc (IVD) in greater depth than ever before. This is an important area of study because degeneration of the lumbar IVDs is associated, perhaps causally, with low back pain: one of the most common and debilitating conditions in the western world. The term degeneration implies an inevitable progression that is characteristic of wear-and-tear-associated conditions. However, modern research on human tissue has shown that this is not the case. Here, disruption of the micro-anatomy that is described as degeneration is an active process, which is probably regulated by locally produced cytokines. This one observation opens up the possibility of inhibiting or even reversing the processes of degeneration. The immediate question is how can the slowly progressive changes of degeneration be treated, particularly as connective tissue repair is thought to be a slow and highly regulated process. In this review, the possibility of using gene therapy as a single-shot, long-lasting therapeutic strategy is discussed, together with an outline of developments in this area to date.

A new, simple, two-step method is introduced for preparing hollow particles that are both pH-responsive and redox sensitive. Hollow poly(methyl methacrylate-co-methacrylic acid) particles swell at moderate pH values, form gels in concentrated dispersions and can be disassembled by adding reducing agents. © 2011 The Royal Society of Chemistry.

Background. Lanthanum carbonate (LC) has been proposed as a new phosphate binder. Presented here are the results from one centre that participated in a multicentre trial to assess the effect of treatment with LC and calcium carbonate (CC) on the evolution of renal osteodystrophy in dialysis patients. Bone biopsies were performed at baseline, after 1 year of treatment and after a further 2-year follow-up period to assess the lanthanum concentration in bone and plasma. Methods. Twenty new dialysis patients were randomized to receive LC (median dose 1250 mg) for 1 year (n ¼ 10), followed by 2 years of CC treatment or CC (n ¼ 10) during the whole study period (3 years). Results. After 36 weeks of treatment, steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml. Six weeks after cessation of 1 year of treatment, the plasma lanthanum levels declined to a value of 0.17 � 0.12 ng/ml (P < 0.05) and after 2 years to 0.09 � 0.03 ng/ml. Plasma and bone lanthanum levels did not correlate with the average lanthanum dose at any time point. The mean bone concentration in patients receiving LC increased from 0.05 � 0.03 to 2.3 � 1.6mg/g (P < 0.05) after 1 year and slightly decreased at the end of the study to 1.9 � 1.6mg/g (P < 0.05). Conclusions. Bone deposition after 1 year of treatment with LC is low (highest concentration: 5.5mg/g). There is a slow release of lanthanum from its bone deposits 2 years after the discontinuation of the treatment and no association with aluminium-like bone toxicity.

Vinyl-functionalised pH-responsive hollow particles have been prepared for the first time and used to construct physical and doubly crosslinked (DX) hydrogels. The pH-responsive DX hydrogels do not redisperse, have a high storage modulus with interconnected porosity and should be useful for regenerative medicine applications. © 2012 The Royal Society of Chemistry.

Recently, our group established a new approach for preparing injectable hydrogels using vinyl-functionalised pH-responsive microgel particles [Liu et al., Soft Matter, 2011, 7, 4696]. pH-responsive microgels swell when the pH approaches the pKa of the particles. Liu et al. used inter-particle crosslinking of vinyl-functionalised microgel particles to prepare hydrogels composed of doubly crosslinked microgels (D-microgels). Here, we combine vinyl-functionalised microgels with added, small-molecule, crosslinkers to prepare high modulus D-microgel/hydrogel (H-X) composites for the first time. The vinyl-functionalised microgel particles used were poly(EA/MAA/BDD)/GM; where, EA MAA, BDD and GM are ethyl acrylate and methacrylic acid, 1,4-butanediol diacrylate and glycidyl methacrylate, respectively. Two added crosslinkers were used to demonstrate the versatility of our approach. They were ethyleneglycol dimethacrylate (EGD) and N,N′-methylenebisacrylamide (BA). We compare the data to control hydrogel composites prepared using non-vinyl-functionalised singly crosslinked microgels (S-microgels). All of the composites showed pH-dependent swelling behaviours and mechanical properties. The storage modulus value for the as-made D-microgel/H-EGD composite was 0.12 MPa and is the highest reported to date for a hydrogel containing pH-responsive microgels. The as-made control S-microgel/H-X composites had high ductilities. Dynamic rheology data were used to determine the effects of vinyl functionalisation on the composite mechanical properties. All of the composites exhibited pH-dependent swelling and a “breathing in” transition occurred. The swollen D-microgel/H-X composites retained their high modulus values upon swelling; although, their ductilities decreased. Because we used two different crosslinkers and pH-responsive microgels containing carboxylic acid groups, the method introduced here for preparing high modulus hydrogel composites should be widely applicable.

Doubly crosslinked microgels (DX MGs) are hydrogels composed of covalently interlinked microgels. They are injectable and have potential application in soft tissue repair. Simple methods for tuning their mechanical properties are required. Here, we investigate the effect of added polyelectrolyte (polycations or a polyanion) as well as NaCl on the mechanical properties of the gels for the first time. Addition of polycations improved ductility and decreased the storage modulus (G′) of the DX MG–polyelectrolyte complex (DX MG–PECs) gels. The best DX MG–PEC gel had a yield strain (γc) of 109%, which is the highest reported to date for any DX MG. Furthermore, our DX MG–PEC gels were robust and maintained high G′ values as well as good ductility when swollen at pH = 7.5. The DX MG–PEC gels with improved ductility contained less than 10% polycation. We also investigated the effect of addition of NaCl solution during DX MG and DX MG–PEC preparation. This caused remarkable increases in both G′ and ductility. The best gel had a G′ of 300 kPa which is the highest elasticity reported for a DX MG to date. Addition of linear polyacrylic acid during DX MG preparation also increased the G′ values. This study has provided three new simple methods for tuning the mechanical properties of DX MGs Because the MGs used here belong to a broad class of polymer colloids the results obtained in this study should be generally applicable.

The ability to tune the mechanical properties of hydrogel composites through the rational design of their constituents has excellent potential for providing advanced hydrogels for regenerative medicine applications. In this study we investigate the morphology and mechanical properties of a new family of pH-responsive hydrogel composites. They were prepared by adding crosslinking monomers (X) to concentrated dispersions of pH-responsive poly(EA/MAA/BDD) (ethylacrylate, methacrylic acid and butanediol diacrylate) MG particles. These MG/X dispersions formed physical gels. The dispersions were then polymerised to give pH-responsive hydrogel composites containing MGs, which are termed here as MG/H-X. The MG particles swelled strongly when the pH exceeded 6.0. The added crosslinking monomers were either ethyleneglycol dimethacrylate (EGD) or poly(ethylene glycol) dimethacrylate (PEGD). The latter had molecular weights in the range of 330 to 750 g/mol. If X had a molecular weight of 330 g/mol, or more, osmotic deswelling of the MG particles occurred. This strongly affected both the gelation behaviour of the MG/X dispersions and the mechanical properties of the chemically crosslinked MG/H-X hydrogel composites. For these new hydrogel composites X acted in two ways; it directed the morphology through osmotic deswelling of the MG particles and also provided a source of crosslinking. The storage modulus of the hydrogel composites was tuneable over a range of five orders of magnitude. The MG/H-X hydrogel composites showed pH-dependent swelling and mechanical properties. The hydrogel composites could also be prepared using poly(EA/MAA/EGD) and poly(EA/MAA/PEGD550) microgels. The simple method introduced here should enable construction of a wide range of pH-responsive hydrogel composites containing microgels with morphologies that can be tuned at the length scale of the MG particles, i.e., about 100 to 500 nm.

pH-Responsive microgel particles are crosslinked polymer colloid particles that swell when the pH approaches the pKa. They have attracted a great deal of interest because of the ability to prepare stimulus responsive dispersions. Microgels that have only one form of crosslinking are termed singly crosslinked microgels (SX microgels). SX microgels are defined here as microgel particles that contain intra-particle linkages as the only source of covalent crosslinks. Recently, we introduced the first examples of a new family of pH-responsive doubly crosslinked microgel (DX microgels) [Liu et al., Soft Matter, 2011, 7, 4696]. DX microgels are hydrogels composed of covalently-linked functionalised SX microgel particles. DX microgels contain inter-particle crosslinking as well as intra-particle crosslinking. Here, we investigate pH-responsive DX microgels prepared using a new, more versatile, microgel functionalisation strategy. Carbodiimide chemistry is used to vinyl-functionalise poly(MMA/MAA/EGDMA) (methyl methacrylate, methacrylic acid and ethyleneglycol dimethacrylate) microgels (abbreviated as M-EGD). The DX microgels were prepared using pH-triggered inter-penetration of 2-aminoethylmethacrylate (AEM) functionalised SX microgels and free-radical crosslinking. The DX microgels based on M-EGD had built-in microporosity. Furthermore, dynamic rheology data show for the first time that the elastic modulus of DX microgels is proportional to the extent of vinyl group functionalisation. The generality of this approach was demonstrated by the preparation of DX microgels based on poly(EA/MAA/BDD) (ethylacrylate and 1, 4-butanediol diacrylate), which is abbreviated as E-BDD. The pH-responsive DX microgels have high elastic modulus values, swell strongly and have low sol fractions. They are injectable and the DX microgels have improved swelling at low pH which should increase the pH range for potential biomaterial applications. The data are compared with those reported by Liu et al. and the differences discussed.

The structure and properties of conventional, singly crosslinked, pH-responsive microgel particles (SX microgels) have been extensively studied. Recently, doubly crosslinked microgels (DX microgels) have been reported. These are a new type of hydrogel that are constructed from covalently linked SX microgels. In this study we report for the first time an investigation of a new class of DX microgels which are pH responsive. The DX microgels were prepared using covalent linking of physically gelled dispersions of inter-penetrating, vinyl-functionalised microgels. The pH-responsive SX microgels used were poly(MMA/MAA/EGDMA) (methyl methacrylate, methacrylic acid and ethyleneglycol dimethacrylate) and poly(EA/MAA/BDDA) (ethylacrylate and butanediol diacrylate). The two microgel types considered (abbreviated as M-EGD and E-BDD) were functionalised with glycidyl methacrylate (GM). pH-triggered swelling of concentrated dispersions and free-radical coupling of the vinyl groups was used to prepare the DX microgels. The relationships between DX microgel composition and mechanical properties are investigated using dynamic rheology and swelling experiments. The DX microgels had storage modulus values of up to 20 kPa at a particle volume fraction (ϕp) of 0.10. The yield strains (γ*) could be varied between 5 and 65%. The ability to tune the mechanical properties of the DX microgels using the degree of functionalisation of the parent GM-functionalised microgel, ϕp and pH is demonstrated. We show that control of intra- and inter-particle crosslinking can be achieved using preparation conditions. The results are explained using a general relationship between the storage modulus and γ*. The new DX microgels have potential application as injectable gels for soft and load-bearing tissue repair.

Controlling hyperphosphatemia in patients with chronic renal failure on renal dialysis is a major problem. None of the available calcium- or aluminum-based phosphate binders match the requirements for an ideal agent, each having its own limitations. The introduction of sevelamer hydrochloride represented a step change in management. Lanthanum carbonate is an alternative nonaluminium, noncalcium phosphate binder. Taken with food, it is well tolerated. It is poorly absorbed and does not require functioning kidneys to be removed from the body. There is no evidence from current studies that it accumulates to biologically significant levels in tissues, but despite the large numbers of patients included in clinical trials, experience with long-term dosing is limited and, as with every new drug used in this type of clinical setting, patients should be carefully monitored as experience with the drug increases. Lanthanum carbonate binds phosphate effectively across the physiological pH range of the upper gastrointestinal tract, and has no detrimental effect on calcium, vitamin D or parathyroid hormone metabolism. From the extensive trial data it seems that lanthanum carbonate is an effective and practical phosphate binder. Lanthanum carbonate and sevelamer are two new oral phosphate binding agents that with others currently in preclinical trials, such as stabilized polynuclear iron idroxide, could well represent a significant breakthrough in the management of hyperphosphatemia in patients with chronic renal failure in whom dietary phosphate restriction and cheaper oral phosphate binding agents prove unsatisfactory. Comparative trials and enhanced clinical experience are needed before the exact place of these competing and complementary therapies can be properly identified in patient management.

Histological diagnosis of renal osteodystrophy. Histology and histomorphometry are the two primary methods of using bone biopsies to diagnose renal osteodystrophy. However, appropriate diagnoses can only be rendered when there is complete understanding of bone structure, of they way bone is processed for histology, and of the manner in which analyses of samples proceeds. In the future, modern applied molecular biology techniques will be added to these standards and redefine diagnoses.