Angiogenic effects of borate glass microfibers in a rodent model.

The primary objective of this research was to evaluate the use of bioactive borate-based glass microfibers for angiogenesis in soft tissue repair applications. The effect of these fibers on growth of capillaries and small blood vessels was compared to that of 45S5 silica glass microfibers and sham implant controls. Compressed mats of three types of glass microfibers were implanted subcutaneously in rats and tissues surrounding the implant sites histologically evaluated 2-4 weeks post surgery. Bioactive borate glass 13-93B3 supplemented with 0.4 wt % copper promoted extensive angiogenesis as compared to silica glass microfibers and sham control tissues. The angiogenic responses suggest the copper-containing 13-93B3 microfibers may be effective for treating chronic soft tissue wounds. A second objective was to assess the possible systemic cytotoxicity of dissolved borate ions and other materials released from implanted borate glass microfibers. Cytotoxicity was assessed via histological evaluation of kidney tissue collected from animals 4 weeks after subcutaneously implanting high amounts of the borate glass microfibers. The evaluation of the kidney tissue from these animals showed no evidence of chronic histopathological changes in the kidney. The overall results indicate the borate glass microfibers are safe and effective for soft tissue applications.

Evaluation of BSA protein release from hollow hydroxyapatite microspheres into PEG hydrogel.

Implants that simultaneously function as an osteoconductive matrix and as a device for local drug or growth factor delivery could provide an attractive system for bone regeneration. In our previous work, we prepared hollow hydroxyapatite (abbreviated HA) microspheres with a high surface area and mesoporous shell wall and studied the release of a model protein, bovine serum albumin (BSA), from the microspheres into phosphate-buffered saline (PBS). The present work is an extension of our previous work to study the release of BSA from similar HA microspheres into a biocompatible hydrogel, poly(ethylene glycol) (PEG). BSA-loaded HA microspheres were placed in a PEG solution which was rapidly gelled using ultraviolet radiation. The BSA release rate into the PEG hydrogel, measured using a spectrophotometric method, was slower than into PBS, and it was dependent on the initial BSA loading and on the microstructure of the microsphere shell wall. A total of 35-40% of the BSA initially loaded into the microspheres was released into PEG over ~14 days. The results indicate that these hollow HA microspheres have promising potential as an osteoconductive device for local drug or growth factor delivery in bone regeneration and in the treatment of bone diseases.

Cytotoxicity assessment of modified bioactive glasses with MLO-A5 osteogenic cells in vitro.

The primary objective of this study was to evaluate in vitro responses of MLO-A5 osteogenic cells to two modifications of the bioactive glass 13-93. The modified glasses, which were designed for use as cell support scaffolds and contained added boron to form the glasses 13-93 B1 and 13-93 B3, were made to accelerate formation of a bioactive hydroxyapatite surface layer and possibly enhance tissue growth. Quantitative MTT cytotoxicity tests revealed no inhibition of growth of MLO-A5 cells incubated with 13-93 glass extracts up to 10 mg/ml, moderate inhibition of growth with 13-93 B1 glass extracts, and noticeable inhibition of growth with 13-93 B3 glass extracts. A morphology-based biocompatibility test was also performed and yielded qualitative assessments of the relative biocompatibilities of glass extracts that agree with those obtained by the quantitative MTT test. However, as a proof of concept experiment, when MLO-A5 cells were seeded onto 13-93 B3 scaffolds in a dynamic in vitro environment, cell proliferation occurred as evidenced by qualitative and quantitative MTT labeling of scaffolds. Together these results demonstrate the in vitro toxicity of released borate ion in static experiments; however borate ion release can be mitigated in a dynamic environment similar to the human body where microvasculature is present. Here we argue that despite toxicity in static environments, boron-containing 13-93 compositions may warrant further study for use in tissue engineering applications.

Evaluation of bone regeneration in implants composed of hollow HA microspheres loaded with transforming growth factor ß1 in a rat calvarial defect model.

Implants that serve simultaneously as an osteoconductive matrix and as a device for local growth factor delivery may be required for optimal bone regeneration in some applications. In the present study, hollow hydroxyapatite (HA) microspheres (106-150µm) in the form of three-dimensional (3-D) scaffolds or individual (loose) microspheres were created using a glass conversion process. The capacity of the implants, with or without transforming growth factor ß1 (TGF-ß1), to regenerate bone in a rat calvarial defect model was compared. The 3-D scaffolds supported the proliferation and alkaline phosphatase activity of osteogenic MLO-A5 cells in vitro, showing their cytocompatibility. Release of TGF-ß1 from the 3-D scaffolds into phosphate-buffered saline ceased after 2-3 days when ∼30% of the growth factor was released. Bone regeneration in the 3-D scaffolds and the individual microspheres increased with time from 6 to 12 weeks, but it was significantly higher (23%) in the individual microspheres than in the 3-D scaffolds (15%) after 12 weeks. Loading with TGF-ß1 (5µg per defect) enhanced bone regeneration in the 3-D scaffolds and individual microspheres after 6 weeks, but had little effect after 12 weeks. 3-D scaffolds and individual microspheres with larger HA diameter (150-250µm) showed better ability to regenerate bone. Based on these results, implants composed of hollow HA microspheres show promising potential as an osteoconductive matrix for local growth factor delivery in bone regeneration.

In vitro performance of 13-93 bioactive glass fiber and trabecular scaffolds with MLO-A5 osteogenic cells.

This in vitro study was performed to evaluate the ability of two types of porous bioactive glass scaffolds to support the growth and differentiation of an established osteogenic cell line. The two scaffold types tested included 13-93 glass fiber and trabecular-like scaffolds seeded with murine MLO-A5 cells and cultured for intervals of 2 to 12 days. Culture in MTT-containing medium showed metabolically active cells both on the surface and within the interior of the scaffolds. Scanning electron microscopy revealed well-attached cells on both types of scaffolds with a continual increase in cell density over a 6-day period. Protein measurements also showed a linear increase in cell density during the incubation. Activity of alkaline phosphatase, a key indicator of osteoblast differentiation, increased about 10-fold during the 6-day incubation with both scaffold types. The addition of mineralization media to MLO-A5 seeded scaffolds triggered extensive formation of alizarin red-positive mineralized extracellular material, additional evidence of cell differentiation and completion of the final step of bone formation on the constructs. Collectively, the results indicate that the 13-93 glass fiber and trabecular scaffolds promote the attachment, growth, and differentiation of MLO-A5 osteogenic cells and could potentially be used for bone tissue engineering applications.

Fabrication of 13-93 bioactive glass scaffolds for bone tissue engineering using indirect selective laser sintering.

Bioactive glasses are promising materials for bone scaffolds due to their ability to assist in tissue regeneration. When implanted in vivo, bioactive glasses can convert into hydroxyapatite, the main mineral constituent of human bone, and form a strong bond with the surrounding tissues, thus providing an advantage over polymer scaffold materials. Bone scaffold fabrication using additive manufacturing techniques can provide control over pore interconnectivity during fabrication of the scaffold, which helps in mimicking human trabecular bone. 13-93 glass, a third-generation bioactive material designed to accelerate the body's natural ability to heal itself, was used in the research described herein to fabricate bone scaffolds using the selective laser sintering (SLS) process. 13-93 glass mixed with stearic acid (as the polymer binder) by ball milling was used as the powder feedstock for the SLS machine. The fabricated green scaffolds underwent binder burnout to remove the stearic acid binder and were then sintered at temperatures between 675 °C and 695 °C. The sintered scaffolds had pore sizes ranging from 300 to 800 µm with 50% apparent porosity and an average compressive strength of 20.4 MPa, which is excellent for non-load bearing applications and among the highest reported for an interconnected porous scaffold fabricated with bioactive glasses using the SLS process. The MTT labeling experiment and measurements of MTT formazan formation are evidence that the rough surface of SLS scaffolds provides a cell-friendly surface capable of supporting robust cell growth.

Hollow hydroxyapatite microspheres as a device for controlled delivery of proteins.

Hollow hydroxyapatite (HA) microspheres were prepared by reacting solid microspheres of Li(2)O-CaO-B(2)O(3) glass (106-150 µm) in K(2)HPO(4) solution, and evaluated as a controlled delivery device for a model protein, bovine serum albumin (BSA). Reaction of the glass microspheres for 2 days in 0.02 M K(2)HPO(4) solution (pH = 9) at 37°C resulted in the formation of biocompatible HA microspheres with a hollow core diameter equal to 0.6 the external diameter, high surface area (~100 m(2)/g), and a mesoporous shell wall (pore size ≈ 13 nm). After loading with a solution of BSA in phosphate-buffered saline (PBS) (5 mg BSA/ml), the release kinetics of BSA from the HA microspheres into a PBS medium were measured using a micro bicinchoninic acid (BCA) protein assay. Release of BSA initially increased linearly with time, but almost ceased after 24-48 h. Modification of the BSA release kinetics was achieved by modifying the microstructure of the as-prepared HA microspheres using a controlled heat treatment (1-24 h at 600-900°C). Sustained release of BSA was achieved over 7-14 days from HA microspheres heated for 5 h at 600°C. The amount of BSA released at a given time was dependent on the concentration of BSA initially loaded into the HA microspheres. These hollow HA microspheres could provide a novel inorganic device for controlled local delivery of proteins and drugs.

In vivo evaluation of 13-93 bioactive glass scaffolds with trabecular and oriented microstructures in a subcutaneous rat implantation model.

The ability of two groups of 13-93 bioactive glass scaffolds to support tissue ingrowth was evaluated after implantation for 4 weeks into subcutaneous pockets in the dorsum of Fisher 344 rats. One group of scaffolds (porosity = 85%; pore size = 100-500 microm) had a "trabecular" microstructure similar to that of dry human trabecular bone, whereas the other group had a "columnar" microstructure of oriented pores (porosity = 65%; pore width = 90-110 microm). Despite the lower porosity and pore width, the columnar scaffolds supported abundant soft tissue ingrowth (glycosaminoglycan and fibrillar stroma), whereas the trabecular scaffolds showed only limited tissue ingrowth. When seeded with mesenchymal stem cells (MSCs), both groups of scaffolds supported abundant tissue infiltration. Bone-like tissue was formed in both groups of scaffolds seeded with MSCs, but not in the scaffolds without MSCs. The new tissues integrated with the hydroxyapatite-like surface layer of the scaffolds which resulted from the conversion of the bioactive glass in the body fluids. The results indicate that the trabecular bioactive glass scaffolds seeded with MSCs, as well as the columnar bioactive glass scaffolds, seeded with MSCs or unseeded, could serve as substrates for bone repair and regeneration.

Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. II. In vitro and in vivo biological evaluation.

In Part I, the in vitro degradation of bioactivAR52115e glass scaffolds with a microstructure similar to that of human trabecular bone, but with three different compositions, was investigated as a function of immersion time in a simulated body fluid. The glasses consisted of a silicate (13-93) composition, a borosilicate composition (designated 13-93B1), and a borate composition (13-93B3), in which one-third or all of the SiO2 content of 13-93 was replaced by B2O3, respectively. This work is an extension of Part I, to investigate the effect of the glass composition on the in vitro response of osteogenic MLO-A5 cells to these scaffolds, and on the ability of the scaffolds to support tissue infiltration in a rat subcutaneous implantation model. The results of assays for cell viability and alkaline phosphatase activity showed that the slower degrading silicate 13-93 and borosilicate 13-93B1 scaffolds were far better than the borate 13-93B3 scaffolds in supporting cell proliferation and function. However, all three groups of scaffolds showed the ability to support tissue infiltration in vivo after implantation for 6 weeks. The results indicate that the required bioactivity and degradation rate may be achieved by substituting an appropriate amount of SiO2 in 13-93 glass with B2O3, and that these trabecular glass scaffolds could serve as substrates for the repair and regeneration of contained bone defects.

Preparation and in vitro evaluation of bioactive glass (13-93) scaffolds with oriented microstructures for repair and regeneration of load-bearing bones.

Bioactive glass (13-93) scaffolds with oriented microstructures, referred to as 'columnar' and 'lamellar', were prepared by unidirectional freezing of suspensions, and evaluated in vitro for potential use in the repair and regeneration of load-bearing bones in vivo. Both groups of scaffolds showed an 'elastic-plastic' mechanical response in compression, large strain for failure (>20%), and strain rate sensitivity, but the columnar scaffolds had the additional advantages of higher strength and larger pore width. At the equivalent porosity (55-60%) and deformation rate (0.5 mm/min), the columnar scaffolds had a compressive strength of 25 +/- 3 MPa, elastic modulus of 1.2 GPa, and pore width of 90-110 microm, compared to values of 10 +/- 2 MPa, 0.4 GPa, and 20-30 microm, respectively, for the lamellar scaffolds. Cellular response to the scaffolds was evaluated using murine MLO-A5 cells, an osteogenic cell line. While the cellular response to both groups of scaffolds was better than control wells, the columnar scaffolds with the larger pore width provided the most favorable substrate for cell proliferation and function. These results indicate that 13-93 bioactive glass scaffolds with the columnar microstructure could be used for the repair and regeneration of load-bearing bones in vivo.

Proliferation and function of MC3T3-E1 cells on freeze-cast hydroxyapatite scaffolds with oriented pore architectures.

Previous work by the authors showed that hydroxyapatite (HA) scaffolds with different types of oriented microstructures and a unique 'elastic-plastic' mechanical response could be prepared by unidirectional freezing of suspensions. The objective of the present work was to evaluate the in vitro cellular response to these freeze-cast HA scaffolds. Unidirectional scaffolds with approximately the same porosity (65-70%) but different pore architectures, described as 'lamellar' (pore width = 25 +/- 5 microm) and 'cellular' (pore diameter = 100 +/- 10 microm), were evaluated. Whereas both groups of scaffolds showed excellent ability to support the proliferation of MC3T3-E1 pre-osteoblastic cells on their surfaces, scaffolds with the cellular-type microstructure showed far better ability to support cell proliferation into the pores and cell function. These results indicate that freeze-cast HA scaffolds with the cellular-type microstructure have better potential for bone repair applications.

Effect of borate glass composition on its conversion to hydroxyapatite and on the proliferation of MC3T3-E1 cells.

Glasses containing varying amounts of B(2)O(3) were prepared by partially or fully replacing the SiO(2) in silicate 45S5 bioactive glass with B(2)O(3). The effects of the B(2)O(3) content of the glass on its conversion to hydroxyapatite (HA) and on the proliferation of MC3T3-E1 cells were investigated in vitro. Conversion of the glasses to HA in dilute (20 mM) K(2)HPO(4) solution was monitored using weight loss and pH measurements. Proliferation of MC3T3-E1 cells was determined qualitatively by assay of cell density at the glass interface after incubation for 1 day and 3 days, and quantitatively by fluorescent measurements of total DNA in cultures incubated for 4 days. Higher B(2)O(3) content of the glass increased the conversion rate to HA, but also resulted in a greater inhibition of cell proliferation under static culture conditions. For a given mass of glass in the culture medium, the inhibition of cell proliferation was alleviated by using glasses with lower B(2)O(3) content, by incubating the cell cultures under dynamic rather than static conditions, or by partially converting the glass to HA prior to cell culture.

Mechanical and in vitro performance of 13-93 bioactive glass scaffolds prepared by a polymer foam replication technique.

A polymer foam replication technique was used to prepare porous scaffolds of 13-93 bioactive glass with a microstructure similar to that of human trabecular bone. The scaffolds, with a porosity of 85+/-2% and pore size of 100-500 microm, had a compressive strength of 11+/-1 MPa, and an elastic modulus of 3.0+/-0.5 GPa, approximately equal to the highest values reported for human trabecular bone. The strength was also considerably higher than the values reported for polymeric, bioactive glass-ceramic and hydroxyapatite constructs prepared by the same technique and with the equivalent level of porosity. The in vitro bioactivity of the scaffolds was observed by the conversion of the glass surface to a nanostructured hydroxyapatite layer within 7 days in simulated body fluid at 37 degrees C. Protein and MTT assays of in vitro cell cultures showed an excellent ability of the scaffolds to support the proliferation of MC3T3-E1 preosteoblastic cells, both on the surface and in the interior of the porous constructs. Scanning electron microscopy showed cells with a closely adhering, well-spread morphology and a continuous increase in cell density on the scaffolds during 6 days of culture. The results indicate that the 13-93 bioactive glass scaffolds could be applied to bone repair and regeneration.

Bioactive borate glass coatings for titanium alloys.

Bioactive borate glass coatings have been developed for titanium and titanium alloys. Glasses from the Na(2)O-CaO-B(2)O(3) system, modified by additions of SiO(2), Al(2)O(3), and P(2)O(5), were characterized and compositions with thermal expansion matches to titanium were identified. Infrared and X-ray diffraction analyses indicate that a hydroxyapatite surface layer forms on the borate glasses after exposure to a simulated body fluid for 2 weeks at 37 degrees C; similar layers form on 45S5 Bioglass((R)) exposed to the same conditions. Assays with MC3T3-E1 pre-osteoblastic cells show the borate glasses exhibit in vitro biocompatibility similar to that of the 45S5 Bioglass((R)). An enameling technique was developed to form adherent borate glass coatings on Ti6Al4V alloy, with adhesive strengths of 36 +/- 2 MPa on polished substrates. The results show these new borate glasses to be promising candidates for forming bioactive coatings on titanium substrates.

Growth and differentiation of osteoblastic cells on 13-93 bioactive glass fibers and scaffolds.

This in vitro study was conducted to evaluate the ability of two types of constructs of bioactive, silica-based 13-93 glass fibers to support the growth and differentiation of MC3T3-E1 osteoblastic cells. The two types of constructs tested included single-layer 13-93 glass fiber rafts and three-dimensional porous scaffolds formed from sintered 13-93 fibers. Scanning electron micrographs showed a closely adhering, well-spread morphology of MC3T3-E1 cells seeded on both types of constructs. The scanning electron microscopy images also showed a continuous increase in cell densities during a 6 day incubation on 13-93 glass fiber rafts and scaffolds. Quantitative fluorescence measurements of DNA also revealed a linear increase in cell density during a 6 day incubation on both types of 13-93 constructs. Examination of scaffolds incubated in MTT containing medium showed the presence of metabolically active viable cells within the interior of the scaffold. The addition of ascorbic acid to MC3T3-E1 cells cultured on the 13-93 glass fibers triggered a threefold increase in alkaline phosphatase, a key indicator of osteoblast differentiation. The sintered scaffolds were found to have open, interconnected pores favorable for tissue ingrowth with a compressive strength similar to cancellous bone. Collectively, the results indicate that 13-93 glass fiber scaffolds are a favorable substrate for the growth and differentiation of osteoblasts and a promising material for bone tissue engineering and repair of bone defects.

Evaluation of barrier creams against sulphur mustard: (II) In vivo and in vitro studies using the domestic white pig.

Previous studies in our laboratory have demonstrated that barrier creams, comprising perfluorinated polymers, are effective against the chemical warfare agent sulphur mustard (SM) when evaluated using human skin in vitro. The purpose of this follow-up study was to further evaluate three candidate (perfluorinated) barrier creams against SM (vapour) using the domestic white pig. The severity and progression of the resulting skin lesions were quantified daily for three weeks post-exposure using biophysical measurements of transepidermal water loss (TEWL) and skin reflectance spectroscopy (SRS). Skin biopsies obtained post-mortem were evaluated by light microscopy and additional skin samples were obtained from adjacent (unexposed) skin sites for a comparative in vitro skin absorption study. Samples of SM vapour within the dosing chambers were measured ex vivo to ascertain the exposure dose (Ct). The three creams were highly effective against SM in vivo (Ct approximately 5000 mg.min.m(-3)): After 3 weeks, barrier cream pre-treated sites were not significantly different from control (unexposed) skin when evaluated by TEWL, SRS or histology. In contrast, skin exposed to SM without pre-treatment showed evidence of persistent damage that was consistent with the slow healing time observed in humans. The amount of SM absorbed in vitro in untreated pig skin was similar to that required to cause comparable lesions in human skin (8-20 and 4-10 microg.cm(-2), respectively), further validating the use of pigs as a toxicologically-relevant dermal model for SM exposure.

Protective ventilation strategies in the management of phosgene-induced acute lung injury.

Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces a life-threatening pulmonary edema within hours of exposure, to which no specific antidote exists. This study aims to examine the pathophysiological changes seen with low tidal volume ventilation (protective ventilation (PV)) strategies compared to conventional ventilation (CV), in a model of phosgene-induced acute lung injury. Anesthetized pigs were instrumented and exposed to phosgene (concentration x time (Ct), 2,350 mg x min x m(-3)) and then ventilated with intermittent positive pressure ventilation (tidal volume (TV) = 10 ml x kg(-1); positive end expiratory pressure, 3 cm H2O; frequency, 20 breaths x min(-1); fractional concentration of inspired oxygen, 0.24), monitored for 6 hours after exposure, and then randomized into treatment groups: CV, PV (A) or (B) (TV, 8 or 6 ml x kg(-1); positive end expiratory pressure, 8 cm H2O; frequency, 20 or 25 breaths x min(-1); fractional concentration of inspired oxygen, 0.4). Pathophysiological parameters were measured for up to 24 hours. The results show that PV resulted in improved oxygenation, decreased shunt fraction, and mortality, with all animals surviving to 24 hours compared to only three of the CV animals. Microscopy confirmed reduced hemorrhage, neutrophilic infiltration, and intra-alveolar edema.

Biodegradable radiation delivery system utilizing glass microspheres and ethylenediaminetetraacetate chelation therapy.

Dysprosium lithium-borate (DyLB) glass microspheres have been developed as a biodegradable radiation delivery vehicle for the treatment of rheumatoid arthritis and other diseases. Radioactive microspheres of these glasses are intended to be injected into a joint infected with rheumatoid arthritis to safely deliver a localized dose (100 Gy) of beta radiation. Once injected, the microspheres react nonuniformly with body fluids. The nonradioactive, lithium-borate component is dissolved from the glass, whereas the radioactive (165)Dy reacts with phosphate anions in the body fluids, and becomes "chemically" trapped in a solid, dysprosium phosphate reaction product that has the same size as the unreacted microsphere. The glass microspheres lose approximately 80% of their weight after nonuniform reaction (<1 day), but the dysprosium phosphate reaction product is slowly metabolized by the body over several months. Ethylenediaminetetraacetate (EDTA) chelation therapy can be used to dissolve the dysprosium phosphate reaction product in vitro in <2 h. The dysprosium phosphate reaction product which formed in vivo in the joint of a Sprague-Dawley rat was also dissolved by EDTA chelation therapy in <1 week, without causing any detectable joint damage. The combination of DyLB glass microspheres and EDTA chelation therapy provides a unique "tool" for the medical community because it can deliver a large dose (>100 Gy) of localized beta radiation to a treatment site within the body, followed by complete biodegradability.

Examination of changes in connective tissue macromolecular components of large white pig skin following application of Lewisite vapour.

The aim of this study was to provide information about the degradative processes that occur in major connective tissue components in skin following exposure of large white pigs to Lewisite vapour. Of particular interest were alterations in glycoproteins, which are known to mediate dermo-epidermal attachment (laminin and type IV collagen) and the main collagen found in the dermis (type III collagen). The immunostaining of transfer blots from skin extracts run on sodium dodecyl sulphate polyacrylamide gel electrophoresis gels revealed no evidence of cross-linking of laminin or of type III or IV collagen. However, there was evidence of a very considerable degradation of laminin and, to a lesser extent, of type IV collagen. Type III collagen did not appear to be degraded in skin exposed to Lewisite. These degradative processes appeared to be more severe than found in previous studies in Yucatan mini-pigs percutaneously exposed to sulphur mustard, in which only laminin was found to undergo partial cleavage rather than wholesale degradation. The results suggest that damage to macromolecular components in the sub-epidermal basement membrane in skin which mediate dermo-epidermal separation processes may be a common feature in the mechanism of action of vesicating agents such as Lewisite and sulphur mustard. It is of interest that the damage to laminin in this study appeared to be more severe than that previously found for sulphur mustard. This suggests that skin can suffer substantial damage yet, in the case of Lewisite exposure, recover relatively quickly. However, Lewisite is not an alkylating agent. Sulphur mustard, in contrast, generates characteristically slow healing lesions, most probably because of its ability to alkylate cell types that normally would be involved in skin regenerative processes.

In vitro and in vivo dissolution behavior of a dysprosium lithium borate glass designed for the radiation synovectomy treatment of rheumatoid arthritis.

Dysprosium lithium borate (DyLB) glass microspheres were investigated for use in the radiation synovectomy treatment of rheumatoid arthritis. In vitro testing focused on weight loss and cation dissolution from glass microspheres immersed in simulated synovial fluid (SSF) at 37 degrees C for up to 64 days. In vivo testing was performed by injecting glass microspheres into the stifle joints of Sprague-Dawley rats and monitoring the biodegradability of the microspheres and the tissue response within the joints. The DyLB microspheres reacted nonuniformly in SSF with the majority of lithium and boron being dissolved, whereas nearly all of the dysprosium (>99.7%) remained in the reacted microspheres. Because the DyLB glasses released negligible amounts of dysprosium while reacting with SSF, they are considered safe for radiation synovectomy from the standpoint of unwanted radiation release from the joint capsule. Furthermore, the DyLB microspheres fragmented, degraded, and reacted with body fluids while in the joints of rats without histologic evidence of joint damage.