Conductive gradient hydrogels allow spatial control of adult stem cell fate.

Electrical gradients are fundamental to physiological processes including cell migration, tissue formation, organ development, and response to injury and regeneration. Current electrical modulation of cells is primarily studied under a uniform electrical field. Here we demonstrate the fabrication of conductive gradient hydrogels (CGGs) that display mechanical properties and varying local electrical gradients mimicking physiological conditions. The electrically-stimulated CGGs enhanced human mesenchymal stem cell (hMSC) viability and attachment. Cells on CGGs under electrical stimulation showed a high expression of neural progenitor markers such as Nestin, GFAP, and Sox2. More importantly, CGGs showed cell differentiation toward oligodendrocyte lineage (Oligo2) in the center of the scaffold where the electric field was uniform with a greater intensity, while cells preferred neuronal lineage (NeuN) on the edge of the scaffold on a varying electric field at lower magnitude. Our data suggest that CGGs can serve as a useful platform to study the effects of electrical gradients on stem cells and potentially provide insights on developing new neural engineering applications.

Culture-Independent Multiplexed Detection of Drug-Resistant Bacteria Using Surface-Enhanced Raman Scattering.

The rapid and accurate detection of bacteria resistance to ß-lactam antibiotics is critical to inform optimal treatment and prevent overprescription of potent antibiotics. Here, we present a fast, culture-independent method for the detection of extended-spectrum ß-lactamases (ESBLs) using surface-enhanced Raman scattering (SERS). The method uses Raman probes that release sulfur-based Raman active molecules in the presence of ß-lactamases. The released thiol molecules can be captured by gold nanoparticles, leading to amplified Raman signals. A broad-spectrum cephalosporin probe R1G and an ESBL-specific probe R3G are designed to enable duplex detection of bacteria expressing broad-spectrum ß-lactamases or ESBLs with a detection limit of 103 cfu/mL in 1 h incubation. Combined with a portable Raman microscope, our culturing-free SERS assay has reduced screening time to 1.5 h without compromising sensitivity and specificity.

Characterization of Photoluminescent Polylactone-Based Nanoparticles for Their Applications in Cardiovascular Diseases.

Cardiovascular diseases (CVD) affect a large number of the population across the globe and are the leading cause of death worldwide. Nanotechnology-based drug delivery has currently offered novel therapeutic options to treat these diseases, yet combination of both diagnostic and therapeutic abilities is further needed to understand factors and/or mechanisms that affect the treatment in order to design better therapies to challenge CVD. Biodegradable photoluminescent polylactones (BPLPLs) enable to bridge this gap as these materials exhibit a stable, long-term intrinsic fluorescence as well as offers excellent cytocompatibility and biodegradability properties. Herein, we formulated three different BPLPL based nanoparticles (NPs), including BPLP-co-poly (L-lactic acid) (BPLPL-PLLA), BPLP-co-poly (lactic-co-glycolic acid) copolymers with lactic acid and glycolic acid ratios of 75:25 (BPLPL-PLGA75:25) and 50:50 (BPLPL-PLGA50:50), and extensively evaluated their suitability as theranostic nanocarriers for CVD applications. All BPLPL based NPs were <160 nm in size and had photoluminescence characteristics and tunable release kinetics of encapsulated protein model depending on polylactones copolymerized with BPLP materials. Compared to BPLPL-PLLA NPs, BPLPL-PLGA NPs demonstrated excellent stability in various formulations including deionized water, serum, saline, and simulated body fluid over 2 days. In vitro cell studies with human umbilical vein derived endothelial cells showed dose-dependent accumulation of BPLPL-based NPs, and BPLPL-PLGA NPs presented superior compatibility with endothelial cells in terms of viability with minimal effects on cellular functions such as nitric oxide production. Furthermore, all BPLPL NPs displayed hemocompatibility with no effect on whole blood kinetic profiles, were non-hemolytic, and consisted of comparable platelet responses such as platelet adhesion and activation to those of PLGA, an FDA approved material. Overall, our results demonstrated that BPLPL-PLGA based NPs have better physical and biological properties than BPLPL-PLLA; hence they have potential to be utilized as functional nanocarriers for therapy and diagnosis of CVD.

Enabling biodegradable functional biomaterials for the management of neurological disorders.

An increasing number of patients are being diagnosed with neurological diseases, but are rarely cured because of the lack of curative therapeutic approaches. This situation creates an urgent clinical need to develop effective diagnosis and treatment strategies for repair and regeneration of injured or diseased neural tissues. In this regard, biodegradable functional biomaterials provide promising solutions to meet this demand owing to their unique responsiveness to external stimulation fields, which enable neuro-imaging, neuro-sensing, specific targeting, hyperthermia treatment, controlled drug delivery, and nerve regeneration. This review discusses recent progress in the research and development of biodegradable functional biomaterials including electroactive biomaterials, magnetic materials and photoactive biomaterials for the management of neurological disorders with emphasis on their applications in bioimaging (photoacoustic imaging, MRI and fluorescence imaging), biosensing (electrochemical sensing, magnetic sensing and opical sensing), and therapy strategies (drug delivery, hyperthermia treatment, and tissue engineering). It is expected that this review will provide an insightful discussion on the roles of biodegradable functional biomaterials in the diagnosis and treatment of neurological diseases, and lead to innovations for the design and development of the next generation biodegradable functional biomaterials.

Development of osteopromotive poly (octamethylene citrate glycerophosphate) for enhanced bone regeneration.

The design and development of bioactive materials that are inherently conducive for osteointegration and bone regeneration with tunable mechanical properties and degradation remains a challenge. Herein, we report the development of a new class of citrate-based materials with glycerophosphate salts, ß-glycerophosphate disodium (ß-GP-Na) and glycerophosphate calcium (GP-Ca), incorporated through a simple and convenient one-pot condensation reaction, which might address the above challenge in the search of suitable orthopedic biomaterials. Tensile strength of the resultant poly (octamethylene citrate glycerophosphate), POC-ßGP-Na and POC-GP-Ca, was as high as 28.2 ±â€¯2.44  MPa and 22.76 ±â€¯1.06  MPa, respectively. The initial modulus ranged from 5.28 ±â€¯0.56  MPa to 256.44 ±â€¯22.88  MPa. The mechanical properties and degradation rate of POC-GP could be controlled by varying the type of salts, and the feeding ratio of salts introduced. Particularly, POC-GP-Ca demonstrated better cytocompatibility and the corresponding composite POC-GP-Ca/hydroxyapatite (HA) also elicited improved osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro, as compared to POC-ßGP-Na/HA and POC/HA. The superior in-vivo performance of POC-GP-Ca/HA microparticle scaffolds in promoting bone regeneration over POC-ßGP-Na/HA and POC/HA was further confirmed in a rabbit femoral condyle defect model. Taken together, the tunability of mechanical properties and degradation rates, together with the osteopromotive nature of POC-GP polymers make these materials, especially POC-GP-Ca well suited for bone tissue engineering applications. STATEMENT OF SIGNIFICANCE: The design and development of bioactive materials that are inherently conducive for osteointegration and bone regeneration with tunable mechanical properties and degradation remains a challenge. Herein, we report the development of a new class of citrate-based materials with glycerophosphate salts, ß-glycerophosphate disodium (ß-GPNa) and glycerophosphate calcium (GPCa), incorporated through a simple and convenient one-pot condensation reaction. The resultant POC-GP polymers showed significantly improved mechanical property and tunable degradation rate. Within the formulation investigated, POC-GPCa/HA composite further demonstrated better bioactivity in favoring osteogenic differentiation of hMSCs in vitro and promoted bone regeneration in rabbit femoral condyle defects. The development of POC-GP expands the repertoire of the well-recognized citrate-based biomaterials to meet the ever-increasing needs for functional biomaterials in tissue engineering and other biomedical applications.

Nanoparticle eluting-angioplasty balloons to treat cardiovascular diseases.

Nanoparticles (NPs) can be used to locally deliver anti-restenosis drugs when they are infused directly to the injured arteries after intervention procedures such as angioplasty. However, the efficacy of transferring NPs via infusion to the arterial wall is limited, at least partially, due to poor NP retention on the inner artery wall. To improve NP retention, angioplasty balloons coated with drug-loaded NPs were fabricated via either layer-by-layer (LbL) electrostatic coating or acrylic-based hydrogel (AAH) coating techniques. Three types of NPs, namely poly (lactide-co-glycolide) (PLGA), biodegradable photo-luminescent PLGA and urethane doped polyester were studied. The transfer efficacy of NPs from various coatings to the arterial wall were further evaluated to find the optimal coating conditions. The ex vivo NP transfer studies showed significantly more NPs being transferred to the rat arterial wall after the angioplasty procedure by the AAH coating (95% transfer efficiency) compared to that of the LbL technique (60%) and dip coating (20%) under flow conditions (10 dyn/cm2). Our results suggest that the AAH coating of drug-loaded NPs on the angioplasty balloon could potentially provide superior retention of drug-loaded NPs onto the arterial wall for a better local delivery of drug-loaded NPs to effectively treat arterial diseases.

Citrate-based materials fuel human stem cells by metabonegenic regulation.

A comprehensive understanding of the key microenvironmental signals regulating bone regeneration is pivotal for the effective design of bioinspired orthopedic materials. Here, we identified citrate as an osteopromotive factor and revealed its metabonegenic role in mediating citrate metabolism and its downstream effects on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our studies show that extracellular citrate uptake through solute carrier family 13, member 5 (SLC13a5) supports osteogenic differentiation via regulation of energy-producing metabolic pathways, leading to elevated cell energy status that fuels the high metabolic demands of hMSC osteodifferentiation. We next identified citrate and phosphoserine (PSer) as a synergistic pair in polymeric design, exhibiting concerted action not only in metabonegenic potential for orthopedic regeneration but also in facile reactivity in a fluorescent system for materials tracking and imaging. We designed a citrate/phosphoserine-based photoluminescent biodegradable polymer (BPLP-PSer), which was fabricated into BPLP-PSer/hydroxyapatite composite microparticulate scaffolds that demonstrated significant improvements in bone regeneration and tissue response in rat femoral-condyle and cranial-defect models. We believe that the present study may inspire the development of new generations of biomimetic biomaterials that better recapitulate the metabolic microenvironments of stem cells to meet the dynamic needs of cellular growth, differentiation, and maturation for use in tissue engineering.

Polymeric biomaterials for biophotonic applications.

With the growing importance of optical techniques in medical diagnosis and treatment, there exists a pressing need to develop and optimize materials platform for biophotonic applications. Particularly, the design of biocompatible and biodegradable materials with desired optical, mechanical, chemical, and biological properties is required to enable clinically relevant biophotonic devices for translating in vitro optical techniques into in situ and in vivo use. This technological trend propels the development of natural and synthetic polymeric biomaterials to replace traditional brittle, nondegradable silica glass based optical materials. In this review, we present an overview of the advances in polymeric optical material development, optical device design and fabrication techniques, and the accompanying applications to imaging, sensing and phototherapy.

Citrate-Based Fluorescent Biomaterials.

Fluorescence imaging has emerged as a promising technique for monitoring and assessing various biologically relevant species in cells and organisms, driving the demand for effective fluorescent agents with good biocompatibility and high fluorescence performance. However, traditional fluorescent agents, such as quantum dots (QDs) and organic dyes, either suffer from toxicity concerns or poor fluorescence performance (e.g., low photobleaching-resistance). In this regard, citrate-based fluorescent biomaterials, which are synthesized from the natural and biocompatible precursor of citric acid (CA), have become competitive alternatives for fluorescence imaging owing to their biocompatibility, cost effectiveness, straightforward synthetic routes, flexible designability, as well as strong fluorescence with adjustable excitation/emission wavelengths. Accordingly, numerous citrate-based biomaterials, including carbon dots (CDs), biodegradable photoluminescent polymers (BPLPs), and small molecular fluorophores, have been developed and researched in the past few decades. This review discusses recent progress in the research and development of citrate-based fluorescent materials with emphasis on their design and synthesis considerations, material properties, fluorescence properties and mechanisms, as well as biomedical applications. It is expected that this review will provide an insightful discussion on the citrate-based fluorescent biomaterials, and lead to innovations for the next generation of fluorescent biomaterials and fluorescence-based biomedical technology.

pH protective Y1 receptor ligand functionalized antiphagocytosis BPLP-WPU micelles for enhanced tumor imaging and therapy with prolonged survival time.

Nanoparticle-based tumor therapies are extensively studied; however, few are capable of improving patient survival time due to premature drug leakage, off target effects, and poor tissue penetration. Previously, we successfully synthesized a novel family of Y1 receptor (Y1R) ligand modified, photoluminescent BPLP nanobubbles and nanoparticles for targeted breast cancer ultrasound imaging; however, increased accumulation could also be observed in the liver, kidney, and spleen, suggesting significant interaction of the particles with macrophages in vivo. Herein, for the first time, we imparted antiphagocytosis capability to Y1R ligand functionalized BPLP-WPU polymeric micelles through the incorporation of a CD47 human glycoprotein based self-peptide. Application of self-peptide modified, DOX loaded micelles in vivo resulted in a 100% survival rate and complete tumor necrosis over 100 days of treatment. In vivo imaging of SPION loaded, self-peptide modified micelles revealed effective targeting to the tumor site while analysis of iron content demonstrated reduced particle accumulation in the liver and kidney, demonstrating reduced macrophage interaction, as well as a 2-fold increase of particles in the tumor. As these results demonstrate, Y1R ligand, self-peptide modified BPLP-WPU micelles are capable of target specific cancer treatment and imaging, making them ideal candidates to improve survival rate and tumor reduction clinically.

Development of Citrate-based Dual-Imaging Enabled Biodegradable Electroactive Polymers.

Increasing occurrences of degenerative diseases, defective tissues and severe cancers heighten the importance of advanced biomedical treatments, which in turn enhance the need for improved biomaterials with versatile theranostic functionalities yet using minimal design complexity. Leveraging the advantages of citrate chemistry, we developed a multifunctional citrate-based biomaterial platform with both imaging and therapeutic capabilities utilizing a facile and efficient one-pot synthesis. The resulting aniline tetramer doped biodegradable photoluminescent polymers (BPLPATs) not only possess programmable degradation profiles (<1 to >6 months) and mechanical strengths (~20 MPa to > 400 MPa), but also present a combination of intrinsic fluorescence, photoacoustic (PA) and electrical conductivity properties. BPLPAT nanoparticles are able to label cells for fluorescence imaging and perform deep tissue detection with PA imaging. Coupled with significant photothermal performance, BPLPAT nanoparticles demonstrate great potential for thermal treatment and in vivo real-time detection of cancers. Our results on BPLPAT scaffolds demonstrate three-dimensional (3D) high-spatial-resolution deep tissue PA imaging (23 mm), as well as promote growth and differentiation of PC-12 nerve cells. We envision that the biodegradable dual-imaging-enabled electroactive citrate-based biomaterial platform will expand the currently available theranostic material systems and open new avenues for diversified biomedical and biological applications via the demonstrated multi-functionality.

Flexible biodegradable citrate-based polymeric step-index optical fiber.

Implanting fiber optical waveguides into tissue or organs for light delivery and collection is among the most effective ways to overcome the issue of tissue turbidity, a long-standing obstacle for biomedical optical technologies. Here, we report a citrate-based material platform with engineerable opto-mechano-biological properties and demonstrate a new type of biodegradable, biocompatible, and low-loss step-index optical fiber for organ-scale light delivery and collection. By leveraging the rich designability and processibility of citrate-based biodegradable polymers, two exemplary biodegradable elastomers with a fine refractive index difference and yet matched mechanical properties and biodegradation profiles were developed. Furthermore, we developed a two-step fabrication method to fabricate flexible and low-loss (0.4 db/cm) optical fibers, and performed systematic characterizations to study optical, spectroscopic, mechanical, and biodegradable properties. In addition, we demonstrated the proof of concept of image transmission through the citrate-based polymeric optical fibers and conducted in vivo deep tissue light delivery and fluorescence sensing in a Sprague-Dawley (SD) rat, laying the groundwork for realizing future implantable devices for long-term implantation where deep-tissue light delivery, sensing and imaging are desired, such as cell, tissue, and scaffold imaging in regenerative medicine and in vivo optogenetic stimulation.

Neuropeptide Y Y1 receptor-mediated biodegradable photoluminescent nanobubbles as ultrasound contrast agents for targeted breast cancer imaging.

Targeted molecular imaging has attracted great attention in cancer diagnosis and treatment. However, most clinically used ultrasound contrast agents (UCAs) are non-targeted microbubbles seldom used for cancer imaging. Here, we fabricated fluorescent nanobubbles (NBs) by encapsulation of liquid tetradecafluorohexane (C6F14) within biodegradable photoluminescent polymers (BPLPs) through an emulsion-evaporation process and conjugation of PNBL-NPY ligand for specific targeting of Y1 receptors overexpressed in breast tumors. The developed PNBL-NPY modified NBs were uniform in size with good dispersibility and photostability, presenting good ultrasound enhancement. Further, in vitro and in vivo results indicated that the fabricated NBs exhibit high affinity and specificity to Y1 receptor-overexpressing breast cancer cells and tumors with minimal toxicity and damage to organs. Our developed PNBL-NPY-modified NBs are novel targeted UCAs for safe, efficient and specific targeted breast cancer imaging, and may provide a new nanoplatform for early cancer diagnosis and treatment in the future.

Click chemistry improved wet adhesion strength of mussel-inspired citrate-based antimicrobial bioadhesives.

For the first time, a convenient copper-catalyzed azide-alkyne cycloaddition (CuAAC, click chemistry) was successfully introduced into injectable citrate-based mussel-inspired bioadhesives (iCMBAs, iCs) to improve both cohesive and wet adhesive strengths and elongate the degradation time, providing numerous advantages in surgical applications. The major challenge in developing such adhesives was the mutual inhibition effect between the oxidant used for crosslinking catechol groups and the Cu(II) reductant used for CuAAC, which was successfully minimized by adding a biocompatible buffering agent typically used in cell culture, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), as a copper chelating agent. Among the investigated formulations, the highest adhesion strength achieved (223.11 ± 15.94 kPa) was around 13 times higher than that of a commercially available fibrin glue (15.4 ± 2.8 kPa). In addition, dual-crosslinked (i.e. click crosslinking and mussel-inspired crosslinking) iCMBAs still preserved considerable antibacterial and antifungal capabilities that are beneficial for the bioadhesives used as hemostatic adhesives or sealants for wound management.

Click Cross-Linking-Improved Waterborne Polymers for Environment-Friendly Coatings and Adhesives.

Waterborne polymers, including waterborne polyurethanes (WPU), polyester dispersions (PED), and polyacrylate emulsions (PAE), are employed as environmentally friendly water-based coatings and adhesives. An efficient, fast, stable, and safe cross-linking strategy is always desirable to impart waterborne polymers with improved mechanical properties and water/solvent/thermal and abrasion resistance. For the first time, click chemistry was introduced into waterborne polymer systems as a cross-linking strategy. Click cross-linking rendered waterborne polymer films with significantly improved tensile strength, hardness, adhesion strength, and water/solvent resistance compared to traditional waterborne polymer films. For example, click cross-linked WPU (WPU-click) has dramatically improved the mechanical strength (tensile strength increased from 0.43 to 6.47 MPa, and Young's modulus increased from 3 to 40 MPa), hardness (increased from 59 to 73.1 MPa), and water resistance (water absorption percentage dropped from 200% to less than 20%); click cross-linked PED (PED-click) film also possessed more than 3 times higher tensile strength (∼28 MPa) than that of normal PED (∼8 MPa). The adhesion strength of click cross-linked PAE (PAE-click) to polypropylene (PP) was also improved (from 3 to 5.5 MPa). In addition, extra click groups can be preserved after click cross-linking for further functionalization of the waterborne polymeric coatings/adhesives. In this work, we have demonstrated that click modification could serve as a convenient and powerful approach to significantly improve the performance of a variety of traditional coatings and adhesives.

Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives.

Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern.

Fluorescence imaging enabled poly(lactide-co-glycolide).

Fluorescent biomaterials have attracted significant research efforts in the past decades. Herein, we report a new series of biodegradable, fluorescence imaging-enabled copolymers, biodegradable photoluminescent poly(lactide-co-glycolide) (BPLP-co-PLGA). Photoluminescence characterization shows that BPLP-co-PLGA solutions, films and nanoparticles all exhibit strong, tunable and stable photoluminescence. By adjusting the molar ratios of L-lactide (LA)/glycolide (GA) and (LA+GA)/BPLP, full degradation of BPLP-co-PLGA can be achieved in 8-16 weeks. The fluorescence decay behavior of BPLP-co-PLGA can be used for non-invasive monitoring of material degradation. In vitro cytotoxicity and in vivo foreign body response evaluations demonstrate that BPLP-co-PLGA exhibits similar biocompatibility to poly(lactide-co-glycolide) (PLGA). The imaging-enabled BPLP-co-PLGA was fabricated into porous scaffolds whose degradation can be monitored through non-invasive imaging and nanoparticles that show theranostic potential demonstrated by fluorescent cellular labeling, imaging and sustained 5-fluorouracil delivery. The development of inherently fluorescent PLGA copolymers is expected to impact the use of already widely accepted PLGA polymers for applications where fluorescent properties are highly desired but limited by the conventional use of cytotoxic quantum dots and photobleaching organic dyes. STATEMENT OF SIGNIFICANCE: This manuscript describes a novel strategy of conferring intrinsic photoluminescence to the widely used biodegradable polymers, poly(lactide-co-glycolide) without introducing any cytotoxic quantum dots or photo-bleaching organic dyes, which may greatly expand the applications of these polymers in where fluorescent properties are highly desired. Given the already significant impact generated by the use of PLGA and alike, this work contributes to fluorescence chemistry and new functional biomaterial design and will potentially generate significant impact on many fields of applications such as tissue engineering, molecular imaging and labeling, and drug delivery.

Osteogenic differentiation of MC3T3-E1 cells on poly(L-lactide)/Fe3O4 nanofibers with static magnetic field exposure.

Proliferation and differentiation of bone-related cells are modulated by many factors such as scaffold design, growth factor, dynamic culture system, and physical simulation. Nanofibrous structure and moderate-intensity (1 mT-1 T) static magnetic field (SMF) have been identified as capable of stimulating proliferation and differentiation of osteoblasts. Herein, magnetic nanofibers were prepared by electrospinning mixture solutions of poly(L-lactide) (PLLA) and ferromagnetic Fe3O4 nanoparticles (NPs). The PLLA/Fe3O4 composite nanofibers demonstrated homogeneous dispersion of Fe3O4 NPs, and their magnetism depended on the contents of Fe3O4 NPs. SMF of 100 mT was applied in the culture of MC3T3-E1 osteoblasts on pure PLLA and PLLA/Fe3O4 composite nanofibers for the purpose of studying the effect of SMF on osteogenic differentiation of osteoblastic cells on magnetic nanofibrous scaffolds. On non-magnetic PLLA nanofibers, the application of external SMF could enhance the proliferation and osteogenic differentiation of MC3T3-E1 cells. In comparison with pure PLLA nanofibers, the incorporation of Fe3O4 NPs could also promote the proliferation and osteogenic differentiation of MC3T3-E1 cells in the absence or presence of external SMF. The marriage of magnetic nanofibers and external SMF was found most effective in accelerating every aspect of biological behaviors of MC3T3-E1 osteoblasts. The findings demonstrated that the magnetic feature of substrate and microenvironment were applicable ways in regulating osteogenesis in bone tissue engineering.

Improving the miscibility of biodegradable polyester/polyphosphazene blends using cross-linkable polyphosphazene.

Biodegradable polyesters and polyphosphazenes are both promising biomaterials for tissue regeneration. A combination of both materials would provide additional advantages over the individual components in aspects of biocompatibility and osteocompatibility. Applications of polyester/polyphosphazene composites, however, were limited due to the severe phase separation. In this study, cross-linkable poly(glycine ethyl ester-co-hydroxyethyl methacrylate)phosphazene (PGHP) was synthesized. It was blended with poly(L-lactide) (PLLA) or poly(L-lactide-co-glycolide) (PLGA), using chloroform as a mutual solvent, and photo-crosslinked before solvent removal. The resulting PLLA (or PLGA)/PGHP composites demonstrated no significant phase separation due to the restricting function of the crosslinked PGHP polymeric network. In comparison with uncrosslinked blends, the mechanical properties of crosslinked composites were remarkably improved, which indicated their strong potential in bone regeneration applications.

Electrospun biodegradable polyorganophosphazene fibrous matrix with poly(dopamine) coating for bone regeneration.

Biodegradable polyphosphazenes were categorized as osteoinductive materials because of their phosphorus-containing feature; however, they were less supportive in cell attachment and proliferation at earlier points in comparison with biodegradable aliphatic polyesters. Therefore, mussel-inspired surface modification of poly(alanine ethyl ester-co-glycine ethyl ester)phosphazene (PAGP) was studied, intending to circumvent the above-mentioned disadvantage of polyphosphazene. To this end, PAGP and poly(L-lactide) (PLLA) were electrospun into nanofibrous substrates and surface treated with dopamine aqueous solution. With the analysis of scanning electron microscope, transmission electron microscope, X-ray photoelectron spectroscope, and Fourier transform infrared spectroscope, the successful poly(dopamine) coating was identified on both PAGP and PLLA nanofibers. MC3T3-E1 osteoblasts were found attaching and proliferating much well on poly(dopamine)-modified nanofibrous substrates in comparison with the pristine ones. In addition, the poly(dopamine) coating demonstrated high activity in promoting osteogenous differentiation. Because the phosphorus content on nanofiber surface was decreased with the poly(dopamine) coating, the poly(dopamine)-coated PAGP nanofibrous substrate was slightly inferior to pure PAGP nanofibrous substrate in osteogenous differentiation. In a summary, the results confirmed that poly(dopamine)-modified polyphosphazenes were promising scaffold materials with both high cell affinity and high osteocompatibility for bone regeneration.