Degradation Of Microspheres Research Articles

Treatment of chronic osteomyelitis with gradient release of DGEA and vancomycin hydrogel-microsphere system and its mechanism

In recent years, the treatment of chronic osteomyelitis mediated by biodegradable polymer platforms has received increasing attention. This paper reports an advanced drug delivery system, vancomycin (VA) and DGEA loaded microspheres embedded in injectable thermosensitive polypeptide hydrogels (i.e., hydrogel-microsphere (Gel-MP) construct), for continuous release of drugs with different mechanisms and more comprehensive treatment of chronic osteomyelitis. The Gel-MP construct exhibits continuous biodegradability and excellent biocompatibility. Microspheres (MP) are wrapped inside Gel. With the degradation of Gel, VA and MP are released from them, VA released with faster degradation speed, achieving a potent antibacterial effect and effectively controlling infection. Due to the slower degradation rate of MP compared to Gel, subsequently, DGEA is released from MP to induce bone formation and produce the effect of filling bone defects. Compared with other formulations, the in vivo combinational treatment of Gel/VA-MP/DGEA can simultaneously balance antibacterial and osteogenic effects. More importantly, local sustained-release drug delivery systems can significantly mitigate the systemic toxicity of drugs. Therefore, the injection local sequential drug delivery system has broad prospects in the clinical application of treating chronic osteomyelitis.

Anaerobic bacterial metabolism responsive microspheres for bacterial embolization cancer therapy

Anaerobic bacteriolytic cancer therapy, whether delivered locally or systemically, frequently encounters challenges related to limited colonization within hypoxic pockets of central tumors and activation of innate immunity. Herein we have developed trans-arterial bacteria embolization therapy using bacterial embolic microspheres. C. novyi-NT spores loaded calcium alginate embolic microspheres demonstrated C. novyi-NT metabolites-mediated microsphere degradation, releasing vegetative C. novyi-NT bacterial in hypoxic condition. Transcatheter directed bacterial microsphere embolization therapy occludes tumor feeding vessels with infused bacterial embolic microspheres and enhances tumoral hypoxia. Notably, anaerobic bacterial metabolism responsive microsphere-bacterial embolization therapy achieved a complete tumor response with enhanced tumor-specific bacterial delivery and colonization, resulting in cancer cell killing across the entire tumor. In vivo tumor response and immunological profiling revealed that bacterial embolization uniquely enhances anti-cancer response, effectively engaging direct anaerobic bacterial oncolysis and adaptive and innate immune responses in a cooperative manner.

Mechanical behavior of glass fiber‐reinforced hollow glass particles filled epoxy composites under moisture environment

AbstractThe utilization of hollow glass particle‐filled fiber‐reinforced composites in marine applications necessitates a proper understanding of their behavior when exposed to moisture environments. In this study, the glass fiber‐reinforced composites reinforced with 0%–30% volume fraction of glass microspheres were fabricated and immersed in seawater and distilled water conditions for monotonic tensile and flexural testing. The degradation mechanisms were analyzed by dynamic mechanical analysis (DMA), Fourier transform infrared spectroscopy (FT‐IR), and scanning electron microscopy (SEM). Moisture absorption results showed an increasing trend with the inclusion of glass microspheres. A decline in glass transition temperature and storage modulus was observed as a result of moisture absorption. The tensile results of the specimens exhibited a decrease of 13% and 9% in distilled water and seawater solution, respectively when compared with unaged samples, respectively. The flexural results of the aged composite specimens demonstrated a reduction of 24% and 11% in distilled water and seawater solution, respectively when compared with unaged samples. The findings also show that the influence of moisture on the modulus is less pronounced compared to its effect on strength under both environmental conditions. The micrograph results revealed a notable deterioration of the glass microsphere and the fiber/matrix interface in the moist environment.Highlights Water absorption increases with the addition of glass microspheres. Microsphere degradation and fiber/matrix debonding are the governing mechanism. Retained 89% of tensile strength of their initial properties after exposed in sea water. Increase in microsphere contents decreases the tensile and flexural strength.

Preparation of poly (butylene adipate-co-butylene terephthalate) microspheres via foam-transfer and investigation of their degradation behavior

Degradable polymer microspheres hold considerable significance for their application in everyday consumer products. In this study, poly (butylene adipate-co-butylene terephthalate) (PBAT) microspheres were synthesized using an improved solvent evaporation method via foam-transfer, and their degradation behavior was subsequently comprehensively examined. Experimental outcomes revealed that optimal conditions, including a PVA concentration of 2.0 wt %, a stirring rate of 600 rpm, a polymer/solvent ratio of 1:16, and a temperature of 45°C, yielded PBAT microspheres through the foam-transfer method with an impressive yield of up to 90 wt %. The degradation of PBAT microspheres was influenced by various factors, including environmental conditions, particle size, and structure. Specifically, PBAT microspheres exhibited heightened degradation when immersed in an acidic environment, possessing smaller particle sizes and a more intricate structure. In a water environment with a pH of 4, PBAT microspheres displayed a degradation rate of 36.16 wt % over a 90-day period. Furthermore, PBAT microspheres with particle sizes ranging from 20 to 30 μm showcased a degradation rate of 49.54 wt % after a 90-day immersion in water at 25°C. Notably, microspheres characterized by substantial porosity, with a porogen to polymer ratio of 180 wt %, exhibited a remarkable degradation rate of 61.66 wt % under the same conditions. As a result, this study offers a promising solution to address the issue of microplastic pollution in everyday consumer products.

Multifunctional Nanofibrous Scaffolds Capable of Localized Delivery of Theranostic Nanoparticles for Postoperative Cancer Management.

Postoperative recovery of cancer patients can be affected by complications, such as tissue dysfunction or disability caused by tissue resection, and also cancer recurrence resulting from residual cancer cells. Despite impressive progress made for tissue engineering scaffolds that assist tissue regeneration for postoperative cancer patients, the majority of existing tissue engineering scaffolds still lack functions for monitoring and killing residual cancer cells, if there are any, upon their detection. In this study, multifunctional scaffolds that comprise biodegradable nanofibers and core-shell structured microspheres encapsulated with theranostic nanoparticles (NPs) are developed. The multifunctional scaffolds possess an extracellular matrix-like nanofibrous architecture and soft tissue-like mechanical properties, making them excellent tissue engineering patch candidates for assisting in the repair and regeneration of tissues at the cancerous sites after surgery. Furthermore, they are capable of localized delivery of theranostic NPs upon quick degradation of core-shell structured microspheres that contain theranostic NPs. Leveraging on folic acid-mediated ligand-receptor binding, surface-enhanced Raman scattering activity, and near-infrared-responsive photothermal effect of the theranostic gold NPs (AuNPs) delivered locally, the multifunctional scaffolds display excellent active targeting, diagnosis, and photothermal therapy functions for cancer cells, showing great promise for adaptive postoperative cancer management.

Preparation and Hydrolytic Degradation of Hydroxyapatite-Filled PLGA Composite Microspheres

Preparation and Hydrolytic Degradation of Hydroxyapatite-Filled PLGA Composite Microspheres

Fabrication of magnesium-doped porous polylactic acid microsphere for bone regeneration.

Biodegradable polymer microspheres that can be used as drug carriers are of great importance in biomedical applications, however, there are still challenges in controllable preparation of microsphere surface morphology and improvement of bioactivity. In this paper, firstly, poly(L-lactic acid) (PLLA) was synthesised by ring-opening polymerisation under anhydrous anaerobic conditions and further combined with the emulsion method, biodegradable PLLA microspheres (PM) with sizes ranging from 60-100 μm and with good sphericity were prepared. In addition, to further improve the surface morphology of PLLA microspheres and enhance their bioactivity, functionalised porous PLLA microspheres loaded with magnesium oxide (MgO)/magnesium carbonate (MgCO3) (PMg) were also prepared by the emulsion method. The results showed that the loading of MgO/MgCO3 resulted in the formation of a porous structure on the surface of the microspheres (PMg) and the dissolved Mg2+ could be released slowly during the degradation of microspheres. In vitro cellular experiments demonstrated the good biocompatibility of PM and PMg, while the released Mg2+ further enhanced the anti-inflammatory effect and osteogenic activity of PMg. Functionalised PMg not only show promise for controlled preparation of drug carriers, but also have translational potential for bone regeneration.

Applicability of alginate-based composite microspheres loaded with aqueous extract of Stevia rebaudiana Bertoni leaves in food and pharmaceutical products

To preserve its favorable health and nutritional qualities under processing conditions and oral ingestion, Stevia rebaudiana Bertoni leaf aqueous extract was encapsulated in composite microspheres based on calcium alginate. The addition of other biopolymers to alginate (ALG) (xanthan gum (XG), casein (CA)) influenced molecular interactions (mainly hydrogen bonding and electrostatic interactions) between microsphere constituents causing the change in microsphere structure and thus physicochemical properties (encapsulation effectiveness and capacity, surface morphology, swelling, stability) as well as the release of total polyphenols (TPC) in distilled water, NaCl solutions and in simulated gastrointestinal fluids.The extent of crosslinking of calcium alginate was altered by blending with XG, CA, or XG + CA, but this did not affect the control mechanism of TPC release detected as diffusion. Results revealed the unsuitability of calcium alginate microspheres for implementation in food products with high water content, while composite microspheres showed desired reduction in TPC release. The best performance (the slowest release and the amount released) for implementation in functional food products containing NaCl exhibited composite microspheres with ALG + XG + CA. The desired prevention of microsphere degradation in simulated gastro fluids was achieved with ALG + XG + CA microspheres, while in simulated intestinal fluids all microspheres were decomposed and completely released TPC.

PEG-fibrinogen hydrogel microspheres as a scaffold for therapeutic delivery of immune cells

Recent advances in the field of cell therapy have proposed new solutions for tissue repair and regeneration using various cell delivery approaches. Here we studied ex vivo a novel topical delivery system of encapsulated cells in hybrid polyethylene glycol-fibrinogen (PEG-Fb) hydrogel microspheres to respiratory tract models. We investigated basic parameters of cell encapsulation, delivery and release in conditions of inflamed and damaged lungs of bacterial-infected mice. The establishment of each step in the study was essential for the proof of concept. We demonstrated co-encapsulation of alveolar macrophages and epithelial cells that were highly viable and equally distributed inside the microspheres. We found that encapsulated macrophages exposed to bacterial endotoxin lipopolysaccharide preserved high viability and secreted moderate levels of TNFα, whereas non-encapsulated cells exhibited a burst TNFα secretion and reduced viability. LPS-exposed encapsulated macrophages exhibited elongated morphology and out-migration capability from microspheres. Microsphere degradation and cell release in inflamed lung environment was studied ex vivo by the incubation of encapsulated macrophages with lung extracts derived from intranasally infected mice with Yersinia pestis, demonstrating the potential in cell targeting and release in inflamed lungs. Finally, we demonstrated microsphere delivery to a multi-component airways-on-chip platform that mimic human nasal, bronchial and alveolar airways in serially connected compartments. This study demonstrates the feasibility in using hydrogel microspheres as an effective method for topical cell delivery to the lungs in the context of pulmonary damage and the need for tissue repair.

Preparation and in vitro release of mPEG-PLA microspheres of Panax notoginseng saponins

This study was performed to promote the clinical application of Panax notoginseng saponins (PNS), which present anti-inflammatory and antitumor activities, and provided insights for the preparation of controlled-release dosage forms of traditional Chinese medicine. A series of drug-loaded microspheres with degradable amphiphilic polymer material polyethylene glycol monomethyl ether-polylactic acid (mPEG-PLA) as the carrier was synthesized. The degradation, sustained-release behavior, and biocompatibility of the drug-loaded microspheres were studied through in vitro release, degradation, hemolysis, anticoagulation, and cytotoxicity experiments. The pharmacological activities of the microspheres were studied through anti-inflammatory and antitumor experiments. The results showed that the best carrier material was mPEG2k-PLA (1:9), with an average particle size of 3.47 ± 0.35 μm, a drug load of 5.50 ± 0.28 %, and an encapsulation efficiency of 38.52 ± 1.93 %. This material could be released stably for approximately 24 days and degrade in approximately 60 days. Moreover, the microspheres had good biocompatibility and anti-inflammatory and antitumor activities.

Initiator enhancement of mandrel degradation for ICF target fabrication

SummaryPoly-α-methylstyrene (PAMS), as an ideal mandrel material used in the fabrication of inertial confinement fusion (ICF) targets, its efficient degradation is the key to the quality of targets. However, there is a great challenge to achieve enhanced degradation. Here, we proposed the strategy to optimize the degradation of PAMS microspheres using di-tert-butyl peroxide (DTBP) as a degradation initiator. Experimentally, monodisperse PAMS microspheres with DTBP were controllably prepared by a microfluidic-based microencapsulation technique. Thermogravimetric results show that DTBP largely decreases the initial degradation temperature from 550 K to 450 K, which effectively promotes the thermal degradation of PAMS microspheres. Theoretically, DTBP can reduce the activation energy of degradation. Moreover, the potential energy surfaces were used to describe the degradation process at the atomic level. Our work brings a new direction for the study of mandrel degradation in ICF targets fabrication, and also provides a valuable reference for solving the pollution of waste plastics.

Microfluidic Fabrication and Characterization of Radiopaque Barium Sulfate Polyethylene Glycol‐Based Hydrogel Microspheres

The objective of this study was to fabricate and characterize monodisperse polyethylene glycol (PEG)‐based barium sulfate hydrogel microspheres for applications in prostatic hyperplasia and prostate cancer treatments. Currently, catheter embolization procedures used in prostatic hyperplasia treatments employ non‐opaque microspheres with a tracer dye, which can result in off‐target embolization. The goal of this study was to fabricate monodisperse, radiopaque microspheres that can be easily tracked via microcomputed tomography (microCT) during embolization procedures. The hydrogel microspheres were fabricated using 4‐arm PEG‐Acrylate macromer and PEG‐dithiol crosslinker solutions in a custom‐designed microfluidic chip that allowed for on‐chip mixing and gelation of a timed‐gelation system, greatly improving bead fabrication throughput and reproducibility. Microspheres were loaded with 1 μm barium sulfate particles and bovine serum albumin to aid in barium suspension. Microspheres were imaged both before and after washing with buffer using an inverted microscope to measure microsphere diameter and degradation. Settling of barium sulfate solutions was measured qualitatively in microcentrifuge tubes. Monodisperse, barium sulfate loaded‐hydrogel microspheres were produced, the size of which could be controlled by modulating the inlet flow rates of the dispersed and continuous phases. Furthermore, the results show that the opacity of the barium sulfate microspheres increased with increased barium sulfate concentration. In conclusion, the results indicate that this study successfully fabricated monodisperse and opaque barium sulfate PEG‐based hydrogel microspheres. Future experiments will evaluate the radiopacity under microCT, swelling and degradation properties, and injectability of the hydrogel microspheres to help further confirm the application of these microspheres in catheter embolization procedures.

Evolution of silicate bioglass particles as porous microspheres with a view towards orthobiologics.

Although FDA approved and clinically utilised, research on 45S5 Bioglass® and S53P4 including other bioactive glasses continues in order to advance their applicability for a range of alternate applications. For example, rendering these particles porous would enable incorporation of varying biological payloads (i.e. cells, drugs and growth factors) and making them spherical would enhance their flow properties enabling delivery to target sites via minimally invasive injection procedures. This paper reports on the manufacture of solid (non-porous; SGMS) and highly porous microspheres (PGMS) with large external pores and fully interconnected porosity from bioactive silicate glass formulations (45S5 and S53P4) via a single stage flame spheroidisation process and their physicochemical properties including in vitro biological response. Morphological and physical characterisation of the SGMS and PGMS revealed interconnected porosity up to 65 ± 5%. Mass loss studies comparing between SGMS and PGMS revealed 1.5 times higher mass loss for the PGMS over 28days. Also, in vitro bioactivity studies using simulated body fluid (SBF) revealed hydroxyapatite (HA) formation at earlier time point for PGMS compared to their SGMS counterparts (i.e day 1 for PGMS and day 3 for SGMS of 45S5). In addition, HA layers were also formed in cell culture media, with the exception of SGMS of 45S5, which revealed CaP formation with a ratio of 1.52-1.78. Direct cell seeding and indirect cell culture studies (via incubation with microsphere degradation products) revealed mouse 3T3 cells were able to grow and undergo osteogenic differentiation in vitro, confirming cytocompatibility of both 45S5 and S53P4 SGMS and PGMS. More importantly and especially for orthobiologic applications, cells were observed to have migrated within the pores of the PGMS. As such, the PGMS developed from these bioactive silicate glasses are highly promising candidate materials for orthobiologics and alternate applications requiring delivery of biologic payloads.

Measuring enzymatic degradation of degradable starch microspheres using confocal laser scanning microscopy

Degradable starch microspheres (DSM) have long been used for topical haemostasis, temporary vascular occlusion and as drug delivery systems. When used for the latter, exact degradation rates of DSM have high importance, as this ensures a controlled and timed drug delivery. Current methods of analysing degradation rates are based on whole batch measurements, which does not yield information regarding individual times of degradation nor does it provide direct correlation measurements between sphere diameter and specific degradation time.In this paper we present an alternative method for measuring degradation rates of biodegradable starch microspheres using confocal laser scanning microscopy (CLSM). We succeeded in visualizing the degradation by staining the DSM and then following the spheres over time in a confocal microscope, after the addition of α-amylase.Individual degradation rates of single spheres could be followed, allowing a precise correlation measure between sphere size and degradation time. Furthermore, physical abnormalities such as internal cavities were detected within some spheres. These physical differences also had a measurable effect on the rate of degradation. Finally, complete degradation rates could be determined very accurately.To our knowledge, this is the first paper in which DSM degradation is visualized and measured using CLSM. Statement of significanceUsing degradable starch microspheres as a drug delivery system, is a continuously evolving field which shows promise in several different areas of illnesses. This paper presents a new method which visualizes enzymatic degradation of starch microspheres in real-time using confocal microscopy. The method is simple, yet the versatility of it suggests that it could be broadly applied within the field of biodegradation. Here, it illuminates a previously uninvestigated parameter: the effect of physical sphere deformities on the rate of degradation. It also provides precise correlation measures between initial sphere size and time of complete degradation.

Can Sodium Thiosulfate Act as a Reversal Agent for Calcium Hydroxylapatite Filler? Results of a Preclinical Study.

IntroductionCalcium hydroxylapatite microspheres suspended in a gel carrier of sodium carboxymethylcellulose (CaHA; Radiesse®) has demonstrated safe and effective restoration of facial volume in clinical trials, as well as collagen biostimulation leading to skin quality improvement. The potential with CaHA, as with any filler, to produce overcorrection and subsequent complications has led to the search for a reversal agent. Sodium thiosulfate (STS) was proposed based on experience with it as a chelating agent to treat calciphylaxis. Previous pilot studies with small sample sizes have suggested its efficacy in the reduction of CaHA volume and nodule formation. The present study focuses on the verification of this effect using various readout methods in preclinical experiments.MethodsWe use both in vitro (co-incubation of STS with CaHA) and in vivo (injections in farm pig) methods with readout techniques such as 3D camera analysis, micro-computed tomography ex vivo (µCT), computed tomography in vivo (CT), histopathology and scanning electron microscopy.ResultsWe did not obtain any indications of CaHA degradation by STS, either in vitro or in vivo. 3D-camera analysis also did not show any decreasing effect of STS on CaHA. However, histology, µCT ex vivo, and CT in vivo indicated a decrease of Radiesse amount/volume after STS treatment, which could be attributed to dispersion effect. It should be noted that necrosis and haemorrhages were observed after STS treatment.DiscussionResults suggest no indication of CaHA microspheres degradation with STS and that the STS mechanism of action on CaHA is consistent with a dispersion effect. Observed necrosis is a further obstacle in the use of STS.

Effect of varying the Mg with Ca content in highly porous phosphate-based glass microspheres

This paper reports on the role of phosphate-based glass (PBG) microspheres and their physicochemical properties including in vitro biological response to human mesenchymal stem cells (hMSCs). Solid and porous microspheres were prepared via a flame spheroidisation process. The Mg content in the PBG formulations explored was reduced from 24 to 2 mol% with a subsequent increase in Ca content. A small quantity of TiO2 (1 mol%) was added to the lower Mg-content glass (2 mol%) to avoid crystallisation. Morphological and physical characterisation of porous microspheres revealed interconnected porosity (up to 76 ± 5 %), average external pore sizes of 55 ± 5 μm with surface areas ranging from 0.38 to 0.43 m2 g−1. Degradation and ion release studies conducted compared the solid (non-porous) and porous microspheres and revealed 1.5 to 2.5 times higher degradation rate for porous microspheres. Also, in vitro bioactivity studies using simulated body fluid (SBF) revealed Ca/P ratios for porous microspheres of all three glass formulations were between 0.75 and 0.92 which were within the range suggested for precipitated amorphous calcium phosphate. Direct cell seeding and indirect cell culture studies (via incubation with microsphere degradation products) revealed hMSCs were able to grow and undergo osteogenic differentiation in vitro, confirming cytocompatibility of the formulations tested. However, the higher Mg content (24 mol%) porous microsphere showed the most potent osteogenic response and is therefore considered as a promising candidate for bone repair applications.

On-demand degradable embolic microspheres for immediate restoration of blood flow during image-guided embolization procedures

Degradable embolic agents that provide transient arterial occlusion during embolization procedures have been of interest for many years. Ideally, embolic agents are visible with standard imaging modalities and offer on-demand degradability, permitting physicians to achieve desired arterial occlusion tailored to patient and procedure indication. Subsequent arterial recanalization potentially enhances the overall safety and efficacy of embolization procedures. Here, we report on-demand degradable and MRI-visible microspheres for embolotherapy. Embolic microspheres composed of calcium alginate and USPIO nanoclusters were synthesized with an air spray atomization and coagulation reservoir equipped with a vacuum suction. An optimized distance between spray nozzle and reservoir allowed uniform size and narrow size distribution of microspheres. The fabricated alginate embolic microspheres crosslinked with Ca2+ demonstrated highly responsive on-demand degradation properties in vitro and in vivo. Finally, the feasibility of using the microspheres for clinical embolization and recanalization procedures was evaluated with interventional radiologists in rabbits. Digital subtraction angiography (DSA) guided embolization of hepatic arteries with these embolic microspheres was successfully performed and the occlusion of artery was confirmed with DSA images and contrast enhanced MRI. T2 MRI visibility of the microspheres allowed to monitor the distribution of intra-arterial (IA) infused embolic microspheres. Subsequent on-demand image-guided recanalization procedures were also successfully performed with rapid degradation of microspheres upon intra-arterial infusion of an ion chelating agent. These instant degradable embolic microspheres will permit effective on-demand embolization/recanalization procedures offering great promise to overcome limitations of currently available permanent and biodegradable embolic agents.

Blending of PLGA-PEG-PLGA for Improving the Erosion and Drug Release Profile of PCL Microspheres.

PCL has a long history as an industrialized biomaterial for preparing microspheres, but its hydrophobic property and slow degradation rate often cause drug degeneration, quite slow drug release rate and undesirable tri-phasic release profile. In this study, we used the blending material of PLGA-PEG-PLGA and PCL to prepare microspheres. The microspheres degradation and drug release behaviors were evaluated through their molecular weight reduction rate, mass loss rate, morphology erosion and drug release profile. The hydrophilic PLGA-PEG-PLGA is expected to improve the degradation and drug release behaviors of PCL microspheres. Microspheres in blending materials exhibited faster erosion rates than pure PCL microspheres, forming holes much quickly on the particle's surface for the drug to diffuse out. A higher proportion of PLGA-PEG-PLGA caused faster degradation and erosion rates. The blending microspheres showed much faster drug release rates than pure PCL microspheres. With blending of 25wt% PLGA-PEG-PLGA, the release rate of microspheres speeded up significantly, while, with a further increase of PLGA-PEG-PLGA proportion (50%, 75%, 100%), it accelerated a little. The microspheres with PCL/PLGA-PEG-PLGA of 1/1 exhibited a linear-like drug release profile. The results could be a guideline for preparing microspheres based on blending materials to obtain a desirable release.

Micro-Clotting of Platelet-Rich Plasma Upon Loading in Hydrogel Microspheres Leads to Prolonged Protein Release and Slower Microsphere Degradation.

Platelet-rich plasma (PRP) is an autologous blood product that contains a variety of growth factors (GFs) that are released upon platelet activation. Despite some therapeutic potential of PRP in vitro, in vivo data are not convincing. Bolus injection of PRP is cleared rapidly from the body diminishing its therapeutic efficacy. This highlights a need for a delivery vehicle for a sustained release of PRP to improve its therapeutic effect. In this study, we used microfluidics to fabricate biodegradable PRP-loaded polyethylene glycol (PEG) microspheres. PRP was incorporated into the microspheres as a lyophilized PRP powder either as is (powder PRP) or first solubilized and pre-clotted to remove clots (liquid PRP). A high PRP loading of 10% w/v was achieved for both PRP preparations. We characterized the properties of the resulting PRP-loaded PEG microspheres including swelling, modulus, degradation, and protein release as a function of PRP loading and preparation. Overall, loading powder PRP into the PEG microspheres significantly affected the properties of microspheres, with the most pronounced effect noted in degradation. We further determined that microsphere degradation in the presence of powder PRP was affected by platelet aggregation and clotting. Platelet aggregation did not prevent but prolonged sustained PRP release from the microspheres. The delivery system developed and characterized herein could be useful for the loading and releasing of PRP to promote tissue regeneration and wound healing or to suppress tissue degeneration in osteoarthritis, and intervertebral disc degeneration.

Abstract No. 690 Magnetic resonance imaging–visible and triggered-degradable nanocomposite microsphere for on-demand temporary embolic agents

Temporary embolization of vessels plays a critical role in many angiographic procedures. However, predictability and reproducibility of vessel recanalization is limited, and in these situations permanent occlusion may be undesirable. The purpose of this study is to evaluate the feasibility of MRI visible and triggered degradable nanocomposite microspheres for a temporary embolic agent. Microspheres composed by superparamagnetic iron oxide nanocluster and alginate were fabricated with spray atomization and coagulation with CaCl2 solution. Size and morphology of the fabricated microspheres with different precursor concentrations and various distance between nozzle and spray were characterized by optical microscope and scanning electron microscope. MR T2 contrast effect of microspheres was measured with 7 T MRI. Triggered degradation of microspheres using various concentration of chelating agents (EDTA) was investigated. In vivo, hepatic arteries of New Zealand white rabbits (n = 3) were occluded by the intra-artery (IA) infused microspheres. Recanalization with a chelating agent were subsequently examined by angiography. The occlusion and recanalization of hepatic arteries were re-confirmed with a perfusion MR in Magnevist contrast-enhanced 3 T MR scans. Uniform-sized microspheres composed by 2%w/v sodium alginate and 5%w/w iron oxide were fabricated with 20 psi spray pressure. Iron oxide contributed to significant MR T2 contrast effect of the microspheres. Chelating agents (∼30 mM) rapidly dissolved the calcium crosslinked microspheres in both water and serum. In vivo angiography demonstrated fast recanalization of embolized right hepatic artery with the chelating agent. Finally, contrast-enhanced MRI showed the occlusion by microspheres and recanalization upon IA infusion of chelating agents. H&E and Prussian blue staining displayed dissolved microspheres in the tumor regions. Nanocomposite microspheres by a simple spray method demonstrated MRI visibility and fast triggered degradation in vitro and in vivo. Further studies will characterize this new on-demand temporary embolic agent.