3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with ß-tricalcium phosphate (ß-TCP) and constructed a bionic cancellous bone scaffolding system α/ß-tricalcium phosphate (α/ß-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100 MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/ß-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants (SCVs). Moreover, microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process, leading to impaired bone defect repair. Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade, challenges remain in clinical management. The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections, but a comprehensive review of their research progress is lacking. This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration, and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

Cyclical endometrial repair and regeneration: Molecular mechanisms, diseases, and therapeutic interventions.

The endometrium is a unique human tissue with an extraordinary ability to undergo a hormone-regulated cycle encompassing shedding, bleeding, scarless repair, and regeneration throughout the female reproductive cycle. The cyclical repair and regeneration of the endometrium manifest as changes in endometrial epithelialization, glandular regeneration, and vascularization. The mechanisms encompass inflammation, coagulation, and fibrinolytic system balance. However, specific conditions such as endometriosis or TCRA treatment can disrupt the process of cyclical endometrial repair and regeneration. There is uncertainty about traditional clinical treatments' efficacy and side effects, and finding new therapeutic interventions is essential. Researchers have made substantial progress in the perspective of regenerative medicine toward maintaining cyclical endometrial repair and regeneration in recent years. Such progress encompasses the integration of biomaterials, tissue-engineered scaffolds, stem cell therapies, and 3D printing. This review analyzes the mechanisms, diseases, and interventions associated with cyclical endometrial repair and regeneration. The review discusses the advantages and disadvantages of the regenerative interventions currently employed in clinical practice. Additionally, it highlights the significant advantages of regenerative medicine in this domain. Finally, we review stem cells and biologics among the available interventions in regenerative medicine, providing insights into future therapeutic strategies.

Evaluation of polyetheretherketone composites modified by calcium silicate and carbon nanotubes for bone regeneration: mechanical properties, biomineralization and induction of osteoblasts.

Desired orthopedic implant materials must have a good biological activity and possess appropriate mechanical property that correspond to those of human bone. Although polyetheretherketone (PEEK) has displayed a promising application prospect in musculoskeletal and dentistry reconstruction thanks to its non-biodegradability and good biocompatibility in the body, the poor osseointegration and insufficient mechanical strength have significantly limited its application in the repair of load-bearing bones and surgical operations. In this study, carbon nanotubes (CNT)/calcium silicate (CS)/polyetheretherketone ternary composites were fabricated for the first time. The addition of CS was mainly aimed at improving biological activities and surface hydrophilicity, but it inevitably compromised the mechanical strength of PEEK. CNT can reinforce the composites even when brittle CS was introduced and further upgraded the biocompatibility of PEEK. The CNT/CS/PEEK composites exhibited higher mechanical strengths in tensile and bending tests, 64% and 90% higher than those of brittle CS/PEEK binary composites. Besides, after incorporation of CNT and CS into PEEK, the hydrophilicity, surface roughness and ability to induce apatite-layer deposition were significantly enhanced. More importantly, the adhesion, proliferation, and osteogenic differentiation of mouse embryo osteoblasts were effectively promoted on CNT/CS/PEEK composites. In contrast to PEEK, these composites exhibited a more satisfactory biocompatibility and osteoinductive activity. Overall, these results demonstrate that ternary CNT/CS/PEEK composites have the potential to serve as a feasible substitute to conventional metal alloys in musculoskeletal regeneration and orthopedic implantation.

3D printed PCLA scaffold with nano-hydroxyapatite coating doped green tea EGCG promotes bone growth and inhibits multidrug-resistant bacteria colonization.

OBJECTIVES: 3D-printing scaffold with specifically customized and biomimetic structures gained significant recent attention in tissue engineering for the regeneration of damaged bone tissues. However, constructed scaffolds that simultaneously promote bone regeneration and in situ inhibit bacterial proliferation remains a great challenge. This study aimed to design a bone repair scaffold with in situ antibacterial functions. MATERIALS AND METHODS: Herein, a general strategy is developed by using epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, firmly anchored in the nano-hydroxyapatite (HA) and coating the 3D printed polymerization of caprolactone and lactide (PCLA) scaffold. Then, we evaluated the stability, mechanical properties, water absorption, biocompatibility, and in vitro antibacterial and osteocyte inductive ability of the scaffolds. RESULTS: The coated scaffold exhibit excellent activity in simultaneously stimulating osteogenic differentiation and in situ resisting methicillin-resistant Staphylococcus aureus colonization in a bone repair environment without antibiotics. Meanwhile, the prepared 3D scaffold has certain mechanical properties (39.3 ± 3.2 MPa), and the applied coating provides the scaffold with remarkable cell adhesion and osteogenic conductivity. CONCLUSION: This study demonstrates that EGCG self-assembled HA coating on PCLA surface could effectively enhance the scaffold's water absorption, osteogenic induction, and antibacterial properties in situ. It provides a new strategy to construct superior performance 3D printed scaffold to promote bone tissue regeneration and combat postoperative infection in situ.

3D-Printed Poly (P-Dioxanone) Stent for Endovascular Application: In Vitro Evaluations.

Rapid formation of innovative, inexpensive, personalized, and quickly reproducible artery bioresorbable stents (BRSs) is significantly important for treating dangerous and sometimes deadly cerebrovascular disorders. It is greatly challenging to give BRSs excellent mechanical properties, biocompatibility, and bioabsorbability. The current BRSs, which are mostly fabricated from poly-l-lactide (PLLA), are usually applied to coronary revascularization but may not be suitable for cerebrovascular revascularization. Here, novel 3D-printed BRSs for cerebrovascular disease enabling anti-stenosis and gradually disappearing after vessel endothelialization are designed and fabricated by combining biocompatible poly (p-dioxanone) (PPDO) and 3D printing technology for the first time. We can control the strut thickness and vessel coverage of BRSs by adjusting the printing parameters to make the size of BRSs suitable for small-diameter vascular use. We added bis-(2,6-diisopropylphenyl) carbodiimide (commercial name: stabaxol®-1) to PPDO to improve its hydrolytic stability without affecting its mechanical properties and biocompatibility. In vitro cell experiments confirmed that endothelial cells can be conveniently seeded and attached to the BRSs and subsequently demonstrated good proliferation ability. Owing to the excellent mechanical properties of the monofilaments fabricated by the PPDO, the 3D-printed BRSs with PPDO monofilaments support desirable flexibility, therefore offering a novel BRS application in the vascular disorders field.

Biocompatible and biodegradable scaffold based on polytrimethylene carbonate-tricalcium phosphate microspheres for tissue engineering.

Biocompatible polymers and drug delivery vehicles have been driving development in bone regeneration. However, most bone scaffolds show poor degradation and proliferation. In this study, a composite microsphere scaffold was prepared using vancomycin hydrochloride(VH)-loaded polytrimethylene carbonate(PTMC) microsphere (PTMC-VH). Adopting a thermal technique, a three-dimensional oleic acid-modified tricalcium phosphate (PTMC-OA-TCP)/PTMC-VH microsphere scaffold was prepared. It had a porosity of 41-47 % and pore size of 129-154 µm. The highest drug loading and release efficiency were obtained with the scaffold produced using 2.4 % polymer concentration and 0.5 %polyvinyl alcohol. The scaffold with PTMC-VH microsphereshad enhancedmechanical properties, water absorption capacity, and degradation. In addition, the PTMC-OA-TCP scaffold had comparable performance with bone cement control in terms of bone regeneration in vivo. In summary, the prepared bioactive scaffolds, which had favorable mechanical properties and facilitated osteogenesis, could be a promising alternative for bone cement in bone tissue engineering.

A new hydrophilic biodegradable ureteral stent restrain encrustation both in vitro and in vivo.

Ureteral stents have been widely used as biomedical devices to treat some urological diseases for several decades. However, the encrustation complications hamper the long-time clinical use of the ureteral stents. In this work, a new type of biodegradable material for the ureteral stents, methoxypoly(ethylene glycol)-block-poly(L-lactide-ran-Ɛ-caprolactone) (mPEG-PLACL), is evaluated to overcome this problem. The results show that the hydrophilicity and degradation rate in artificial urine of mPEG-PLACL are both significantly increased. It is worth noting that the mPEG-PLACL shows a lower amount of encrustation after immersing the stents in the dynamic urinary extracorporeal circulation (DUEC) model for 7 days. In addition, 71% Ca and 92% Mg are inhibited in vivo by quantitative analysis. Pathological analysis exhibit that the mPEG-PLACL cause less diffuse mucosal hyperplasia after 7 weeks of implantation. All the results indicate that this new type of biodegradable material had an excellent potential for the ureteral stents in the future.

Chitosan-coated hydroxyapatite and drug-loaded polytrimethylene carbonate/polylactic acid scaffold for enhancing bone regeneration.

Biocompatible polymers and drug-delivery scaffolds have driven development in bone regeneration. In this study, we fabricated a chitosan (CS)-coated polytrimethylene carbonate (PTMC)/polylactic acid (PLLA)/oleic acid-modified hydroxyapatite (OA-HA)/vancomycin hydrochloride (VH) microsphere scaffold for drug release with excellent biocompatibility. The incorporation of PLLA, OA-HA, and VH into PTMC microspheres not only slowed the biodegradability of the scaffold but also enhanced its mechanical properties and surface properties. Moreover, the CS coating stimulated extensive adhesion of osteoblasts before OA-HA incorporation, which facilitated the controlled release of OA-HA. The scaffolds were characterized via scanning electron microscopy, in vitro comprehensive performance testing, cell culturing, and microcomputer tomography scanning. The results indicated that the surface of the composite microsphere scaffold was suitable for osteoblast adhesion. Additionally, the release of OA-HA stimulated osteogenic proliferation. Our findings suggest that the CS-PTMC/PLLA/OA-HA/VH microsphere scaffold is promising for bone tissue engineering applications.

Biodegradable poly (lactic acid-co-trimethylene carbonate)/chitosan microsphere scaffold with shape-memory effect for bone tissue engineering.

Poly (lactic acid) (PLA), although extensively used as biomedical materials, has the distinct disadvantage of producing acidic byproducts which can lead to tissue inflammatory reactions and clinic failure. Here we presented a combination of Poly (lactic acid-co-trimethylene carbonate) and natural polymer chitosan, improving its compression resilience and reducing its acidic byproducts. In this case, we developed 3D scaffolds using solvent/nonsolvent technique sintered PLA-TMC and PLA-TMC/Chitosan microspheres with selected particle size (355-500 µm). By controlling the preparation methods and parameters, the porosity, pore size and mechanical properties of microsphere scaffolds can be designed and controlled. Strikingly, PLA-TMC/15 % Chitosan microsphere scaffolds possess shape-memory effect and rapidly recovered to initial shape when heated to 37℃ within 300 s. The microsphere scaffolds had a 3D porous architecture with pore size ranging from 105.67 ± 12.51 µm to 129.69 ± 11.39 µm. The mechanical and physicochemical properties of microspheres and scaffolds were characterized in details. Moreover, all microsphere scaffolds were qualified as their compressive modulus (120.36 MPa -195.32 MPa) matched the cancellous bone during 16 weeks degradation. Furthermore, CCK8 cell proliferation assay and ALP activity assay verified that the scaffolds were non-toxic and conductive to cell adhesion. The scaffolds are expected to be used in bone regeneration and bone repair field.

The Preparation, Characterization, Mechanical and Antibacterial Properties of GO-ZnO Nanocomposites with a Poly(l-lactide)-Modified Surface.

Graphene oxide (GO) was employed for the preparation of GO-zinc oxide (ZnO). The hydroxyl group on the surface was exploited to trigger the l-lactide ring-opening polymerization. A composite material with poly(l-lactide) (PLLA) chains grafted to the GO-ZnO surface, GO-ZnO-PLLA, was prepared. The results demonstrated that the employed method allowed one-step, rapid grafting of PLLA to the GO-ZnO surface. The chemical structure of the GO surface was altered by improved dispersion of GO-ZnO in organic solvents, thus enhancing the GO-ZnO dispersion in the PLLA matrix and the interface bonding with PLLA. Subsequently, composite films, GO-ZnO-PLLA and GO-ZnO-PLLA/PLLA, were prepared. The changes in interface properties and mechanical properties were studied. Furthermore, the antibacterial performance of nano-ZnO was investigated.

Functionalization of Graphene Oxide with Low Molecular Weight Poly (Lactic Acid).

In this paper, the hydroxyl groups on the surface of graphene oxide (GO) were used to initiate the ring-opening polymerization of a lactic acid O-carboxyanhydride. GO grafted with poly (l-lactic acid) molecular chains (GO-g-PLLA) was prepared. Lactic acid O-carboxyanhydride has a higher polymerization activity under mild polymerization conditions. Thus, the functionalization of the polymer chains and obtaining poly (lactic acid) (PLLA) was easily achieved by ring-opening polymerization with 4-dimethylaminopyridine (DMAP) as the catalyst. The results showed that with this method, PLLA can be rapidly grafted to the surface of GO in one step. As a result, the chemical structure of the GO surface was altered, improving its dispersion in organic solvents and in a PLLA matrix, as well as its bonding strength with the PLLA interface. We then prepared GO/PLLA and PLLA/GO-g-PLLA composite materials and investigated the differences in their interfacial properties and mechanical properties. GO-g-PLLA exhibited excellent dispersion in the PLLA matrix and formed excellent interfacial bonds with PLLA through mechanical interlocking, demonstrating a significant enhancement effect compared to PLLA. The water vapor and oxygen permeabilities of the GO-g-PLLA/PLLA composite decreased by 19% and 29%, respectively.

Preparation, mechanical properties and in vitro cytocompatibility of multi-walled carbon nanotubes/poly(etheretherketone) nanocomposites.

Desired bone repair material must have excellent biocompatibility and high bioactivity. Moreover, mechanical properties of biomaterial should be equivalent to those of human bones. For developing an alternative biocomposite for load-bearing orthopedic application, combination of bioactive fillers with polymer matrix is a feasible approach. In this study, a series of multi-walled carbon nanotubes (MWCNTs)/poly(etheretherketone) (PEEK) bioactive nanocomposites were prepared by a novel coprecipitation-compounding and injection-molding process. Scanning electron microscope (SEM) images revealed that MWCNTs were adsorbed on the surface of PEEK particles during the coprecipitation-compounding process and dispersed homogeneously in the nanocomposite because the conjugated PEEK polymers stabilized MWCNTs by forming strong π-π stack interactions. The mechanical testing revealed that mechanical performance of PEEK was significantly improved by adding MWCNTs (2-8 wt%) and the experimental values obtained were close to or higher than that of human cortical bone. In addition, incorporation of MWCNTs into PEEK matrix also enhanced the roughness and hydrophilicity of the nanocomposite surface. In vitro cytocompatibility tests demonstrated that the MWCNTs/PEEK nanocomposite was in favor of cell adhesion and proliferation of MC3T3-E1 osteoblast cells, exhibiting excellent cytocompatibility and biocompatibility. Thus, this MWCNTs/PEEK nanocomposite may be used as a promising bone repair material in orthopedic implants application.

Preparation and characterization of a novel degradable nano-hydroxyapatite/poly(lactic-co-glycolic) composite reinforced with bamboo fiber.

It is a promising and challenging to achieve an ideal poly (lactic-co-glycolic) (PLGA)-based composite. In this paper, bamboo fiber (BF) was firstly designed to incorporate into nano-hydroxyapatite/PLGA (n-HA/PLGA) composite, and a series of novel biodegradable BF/n-HA/PLGA ternary composites with different BF amounts (0wt%, 5wt%, 10wt% and 20wt%) were prepared by solution mixing method. The effect of BF content on the crystallization behavior, interface structure and mechanical property of BF/n-HA/PLGA ternary composite was investigated by X-ray diffraction pattern (XRD), differential scanning calorimeter (DSC) and scanning electron microscope (SEM), comparing with pure PLGA and n-HA/PLGA composite. The results showed that BF further promoted the crystallization of PLGA acting as a heterogeneous nucleation agent, and the addition of 10wt% BF was the best benefit to promote the crystallization. However, the higher addition content of BF caused more agglomeration in n-HA/PLGA matrix, which decreased gradually the mechanical properties of the BF/n-HA/PLGA composite. In conclusion, the addition content of 5wt% BF to n-HA/PLGA matrix was an appropriate proportion, which can achieved the best mechanical reinforce effectiveness, suggesting that BF/n-HA/PLGA composite had more potential in biomedical application than n-HA/PLGA composite.

Preparation and Properties of Bamboo Fiber/Nano-hydroxyapatite/Poly(lactic-co-glycolic) Composite Scaffold for Bone Tissue Engineering.

In this study, bamboo fiber was first designed to incorporate into nano-hydroxyapatite/poly(lactic-co-glycolic) to obtain a new composite scaffold of bamboo fiber/nano-hydroxyapatite/poly(lactic-co- glycolic) (BF/n-HA/PLGA) by freeze-drying method. The effect of their components and some factors consisting of different freeze temperatures, concentrations, and pore-forming agents on the porous morphology, porosity, and compressive properties of the scaffold were investigated by scanning electron microscope, modified liquid displacement method, and electromechanical universal testing machine. The results indicated that the 5% BF/30% n-HA/PLGA composite scaffold, prepared with 5% (w/v) high concentration and frozen at -20 °C without pore-forming agent, had the best ideal porous structure and porosity as well as compressive properties, which far exceed those of n-HA/PLGA composite scaffold. In addition, the in vitro simulated body fluids soaking and cell culture experiment showed the addition of BF into the scaffold accelerated the BF/n-HA/PLGA composite scaffolds degradation and exhibited good cytocompatibility, including attachment and proliferation. All the results of the study show that BF has improved the properties of n-HA/PLGA composite scaffolds and BF/n-HA/PLGA might have a great potential for bone tissue engineering scaffold.

Improving the degradation behavior and in vitro biological property of nano-hydroxyapatite surface- grafted with the assist of citric acid.

To obtain ideal nano-hydroxyapatite(n-HA) filler for poly(lactide-co-glycolide) (PLGA), a new surface-grafting with the assist of citric acid for nano-hydroxyapatite (n-HA) was designed, and the effect of n-HA surface-grafted with or without citric acid on in vitro degradation behavior and cells viability was studied by the experiments of soaking in simulated body fluid (SBF) and incubating with human osteoblast-like cells (MG-63). The change of pH value, tensile strength reduction, the surface deposits, cells attachment and proliferation of samples during the soaking and incubation were investigated by means of pH meter, electromechanical universal tester, scanning electron microscope (SEM) coupled with energy-dispersive spectro-scopy (EDS), fluorescence microscope and MTT method. The results showed that the introduction of citric acid not only delayed the strength reduction during the degradation by inhibiting the detachment of n-HA from PLGA, but also endowed it better cell attachment and proliferation, suggesting that the n-HA surface-grafted with the assist of citric acid was an important bioactive ceramic fillers for PLGA used as bone materials.

Bone-like apatite coating on functionalized poly(etheretherketone) surface via tailored silanization layers technique.

Poly(etheretherketone) (PEEK) is a rigid semi-crystalline polymer with outstanding mechanical properties, bone-like stiffness and suitable biocompatibility that has attracted much interest as a biomaterial for orthopedic and dental implants. However, the bio-inert surface of PEEK limits its biomedical applications when direct osteointegration between the implants and the host tissue is desired. In this work, -PO4H2, -COOH and -OH groups were introduced on the PEEK surface by further chemical treatments of the vinyl-terminated silanization layers formed on the hydroxylation-pretreated PEEK surface. Both the surface-functionalized and pristine specimens were characterized by X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and water contact angle measurements. When placed in 1.5 strength simulated body fluid (SBF) solution, apatite was observed to form uniformly on the functionalized PEEK surface and firmly attach to the substrate. The characterized results demonstrated that the coating was constituted by poorly crystallized bone-like apatite and the effect of surface functional groups on coating formation was also discussed in detail. In addition, in vitro biocompatibility of PEEK, in terms of pre-osteoblast cell (MC3T3-E1) attachment, spreading and proliferation, was remarkably enhanced by the bone-like apatite coating. Thus, this study provides a method to enhance the bioactivity of PEEK and expand its applications in orthopedic and dental implants.

Mechanism of inhibition on L929 rat fibroblasts proliferation induced by potential adhesion barrier material poly(p-dioxanone-co-L-phenylalanine) electrospun membranes.

Fibroblast plays an important role in the occurrence of postoperative tissue adhesion; materials that have particular "cell-material" interactions to inhibit proliferation of fibroblast will be excellent potential adhesion barriers. In the current study, we synthesized copolymers of p-dioxanone and L-phenylalanine (PDPA) and evaluated the mechanism of its particular inhibition effect on L929 fibroblast proliferation when used as a culture surface. PDPA electrospun membranes could induce apoptosis of L929 fibroblasts. We hypothesized there were two reasons for the apoptosis induction: one was the ability to facilitate cell adhesion of materials, and the other was production of the degradation product, L-phenylalanine. Ninhydrin colorimetric results revealed that L-phenylalanine was continuously released during the culture process and could induce apoptosis in L929 cells. Relatively poor cell adhesion and constant release of L-phenylalanine made PDPA-1 to be the most efficient polymer for the induction of apoptosis. Analysis of apoptosis-related genes revealed that PDPA-induced apoptosis might be performed in a mitochondrial-dependent pathway. But poly(p-dioxanone)-induced apoptosis might occur in a c-Myc independent pathway that was different from PDPA.

Cellular responses to electrospun membranes made from blends of PLLGA with PEG and PLLGA-b-PEG.

Control of cellular responses is crucial for the use of electrospun membranes in biomedical applications, including tissue engineering or biomedical devices. However, it is still unclear whether adhesion and proliferation of fibroblasts is stimulated or inhibited on polyethylene glycol (PEG)-modified electrospun membranes. In this study, poly(L-lactide-co-glycolide) (PLLGA)-PEG copolymer and pure PEG were blended with PLLGA, and then electrospun onto nonwoven membranes. The effects of blending of PLLGA-PEG or pure PEG on the adsorption of proteins, and further on the adhesion and proliferation of L929 fibroblasts on the electrospun membranes were investigated. Addition of PLLGA-PEG or PEG significantly improved the hydrophilicity of the electrospun membranes. Pure PEG had no obvious effects on the growth of L929 fibroblasts; in contrast, PLLGA-PEG significantly inhibited the adsorption of proteins and the proliferations of the cells on the electrospun membranes. In response to diminished protein adsorption, mRNA expression of genes related to cell adhesion and migration was up-regulated. The limited effects of pure PEG were probably caused by its preferential dissolution, whereas membrane-confined PLLGA-PEG displayed excellent performance on the inhibition of protein adsorption and cell proliferation.

Synthesis of citrate-stabilized hydrocolloids of hydroxyapatite through a novel two-stage method: a possible aggregates-breakdown mechanism of colloid formation.

Long-term stable (>2 years) hydrocolloids of hydroxyapatite (HA) were synthesized via a low-temperature (18-50 °C) reaction of aqueous ammonium phosphate with calcium nitrate in the presence of citrate ions, followed by an aging process at high temperature (80-99 °C) for 4 h. Changing the reaction and/or aging temperature seldom yielded stable HA hydrocolloids. The as-prepared hydrocolloids were desalinated through ultrafiltration where their average particle size gradually decreased, bottomed out at 100-400 µS/cm, and sharply increased in parallel with a decrease in solution conductivity. The colloid formation is most likely through a temperature-sensitive aggregates-breakdown process. During low-temperature reaction, citrate-calcium chelation bridges the growing HA particles into loose aggregates. High-temperature aging disrupts these inter-particle links and thus breaks the aggregates, imparting negative charges to the HA, forming colloidal particles stabilized by surface charge. The decrease in mean particle size during early ultrafiltration suggested that the aggregate breakdown further proceeded through desalination. In conclusion, the temperature-dependent interactions between citrate ions and calcium sites on HA particles played key roles in the synthesis and stability of the HA colloids.