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The burden of bone fractures demands development of effective biomaterial solutions, while additional acute events such as noncompressible bleeding further motivate the search for multi-functional implants to avoid complications including osseous hemorrhage, infection, and nonunion. Bone wax has been widely used in orthopedic bleeding control due to its simplicity of use and conformation to irregular defects; however, its nondegradability results in impaired bone healing, risk of infection, and significant inflammatory responses. Herein, a class of intrinsically fluorescent, osteopromotive citrate-based polymer/hydroxyapatite (HA) composites (BPLP-Ser/HA) as a highly malleable press-fit putty is designed. BPLP-Ser/HA putty displays mechanics replicating early nonmineralized bone (initial moduli from ≈2-500 kPa), hydration induced mechanical strengthening in physiological conditions, tunable degradation rates (over 2 months), low swelling ratios (<10%), clotting and hemostatic sealing potential (resistant to blood pressure for >24 h) and significant adhesion to bone (≈350-550 kPa). Simultaneously, citrate's bioactive properties result in antimicrobial (≈100% and 55% inhibition of S. aureus and E. coli) and osteopromotive effects. Finally, BPLP-Ser/HA putty demonstrates in vivo regeneration in a critical-sized rat calvaria model equivalent to gold standard autograft. BPLP-Ser/HA putty represents a simple, off-the-shelf solution to the combined challenges of acute wound management and subsequent bone regeneration.
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Sustitutos de Huesos , Ácido Cítrico , Animales , Regeneración Ósea , Huesos , Citratos , Durapatita , Escherichia coli , Ratas , Staphylococcus aureusRESUMEN
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.
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Embedded printing has emerged as a valuable tool for fabricating complex structures and microfluidic devices. Currently, an ample of amount of research is going on to develop new materials to advance its capabilities and increase its potential applications. Here, we demonstrate a novel, transparent, printable, photocrosslinkable, and tuneable silicone composite that can be utilized as a support bath or an extrudable ink for embedded printing. Its properties can be tuned to achieve ideal rheological properties, such as optimal self-recovery and yield stress, for use in 3D printing. When used as a support bath, it facilitated the generation microfluidic devices with circular channels of diameter up to 30 µm. To demonstrate its utility, flow focusing microfluidic devices were fabricated for generation of Janus microrods, which can be easily modified for multitude of applications. When used as an extrudable ink, 3D printing of complex-shaped constructs were achieved with integrated electronics, which greatly extends its potential applications towards soft robotics. Further, its biocompatibility was tested with multiple cell types to validate its applicability for tissue engineering. Altogether, this material offers a myriad of potential applications (i.e., soft robotics, microfluidics, bioprinting) by providing a facile approach to develop complicated 3D structures and interconnected channels.
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Citrate-based biodegradable polymers have emerged as a distinctive biomaterial platform with tremendous potential for diverse medical applications. By harnessing their versatile chemistry, these polymers exhibit a wide range of material and bioactive properties, enabling them to regulate cell metabolism and stem cell differentiation through energy metabolism, metabonegenesis, angiogenesis, and immunomodulation. Moreover, the recent US Food and Drug Administration (FDA) clearance of the biodegradable poly(octamethylene citrate) (POC)/hydroxyapatite-based orthopedic fixation devices represents a translational research milestone for biomaterial science. POC joins a short list of biodegradable synthetic polymers that have ever been authorized by the FDA for use in humans. The clinical success of POC has sparked enthusiasm and accelerated the development of next-generation citrate-based biomaterials. This review presents a comprehensive, forward-thinking discussion on the pivotal role of citrate chemistry and metabolism in various tissue regeneration and on the development of functional citrate-based metabotissugenic biomaterials for regenerative engineering applications.
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Materiales Biocompatibles , Ácido Cítrico , Humanos , Ácido Cítrico/química , Materiales Biocompatibles/química , Animales , Ingeniería de Tejidos/métodos , Polímeros/química , Durapatita/química , Durapatita/metabolismoRESUMEN
The revolutionary role of tissue adhesives in wound closure, tissue sealing, and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing. In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators (exemplified by sodium periodate and silver nitrate), herein, the natural polyphenolic compound tannic acid (TA) was used to achieve near instantaneous (<25s), hydrogen bond mediated gelation of citrate-based mussel-inspired bioadhesives combining anti-oxidant, anti-inflammatory, and antimicrobial activities (3A-TCMBAs). The resulting materials were self-healing and possessed low swelling ratios (<60%) as well as considerable mechanical strength (up to â¼1.0 MPa), elasticity (elongation â¼2700%), and adhesion (up to 40 kPa). The 3A-TCMBAs showed strong in vitro and in vivo anti-oxidant ability, favorable cytocompatibility and cell migration, as well as photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli (>90% bacterial death upon near-infrared (NIR) irradiation). In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs + NIR treatment could promote wound closure and collagen deposition and improve the collagen I/III ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines. Further, phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation & remodeling of the extracellular matrix (ECM) in the late stage (supported by phased CD31 (platelet endothelial cell adhesion molecule-1) PDGF (platelet-derived growth factor) and VEGF (vascular endothelial growth factor) expression as well as elevated matrix metalloprotein-9 (MMP-9) expression on day 21), resulting in scarless wound healing. The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant, new class of bioadhesive.
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The high demand for rapid wound healing has spurred the development of multifunctional and smart bioadhesives with strong bioadhesion, antibacterial effect, real-time sensing, wireless communication, and on-demand treatment capabilities. Bioadhesives with bio-inspired structures and chemicals have shown unprecedented adhesion strengths, as well as tunable optical, electrical, and bio-dissolvable properties. Accelerated wound healing has been achieved via directly released antibacterial and growth factors, material or drug-induced host immune responses, and delivery of curative cells. Most recently, the integration of biosensing and treatment modules with wireless units in a closed-loop system yielded smart bioadhesives, allowing real-time sensing of the physiological conditions (e.g., pH, temperature, uric acid, glucose, and cytokine) with iterative feedback for drastically enhanced, stage-specific wound healing by triggering drug delivery and treatment to avoid infection or prolonged inflammation. Despite rapid advances in the burgeoning field, challenges still exist in the design and fabrication of integrated systems, particularly for chronic wounds, presenting significant opportunities for the future development of next-generation smart materials and systems.
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Embedded printing has emerged as a valuable tool for fabricating complex structures and microfluidic devices. Currently, an ample of amount of research is going on to develop new materials to advance its capabilities and increase its potential applications. Here, we demonstrate a novel, transparent, 3D printable, photocrosslinkable, and tuneable silicone composite that can be utilized as a support bath or an extrudable ink for embedded printing. The proposed silicone composite can be tuned to achieve ideal rheological properties, such as optimal self-recovery and yield stress, for use in 3D printing. When used as a support bath, it facilitated the generation microfluidic devices with circular channels of diameter up to 30 µm. To demonstrate its utility, flow focusing microfluidic devices were fabricated for generation of Janus microrods, which can be easily modified for multitude of applications. When used as an extrudable ink, 3D printing of complex-shaped micro- and macro-constructs were achieved with integrated electronics, which greatly extends its potential applications towards developing complex flexible parts for soft robotics and prosthetics. Further, its biocompatibility was tested with multiple cell types to validate its applicability for medical and tissue engineering use. Altogether, this material offers a myriad of potential applications in material and medical fields by providing a facile approach to develop complicated 3D structures and interconnected channels that can further advance microfluidics and soft-robotics research.
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Tissue adhesives are commonly used in surgeries and regenerative engineering for the repair and regeneration of topical and internal wounds on tissues and organs such as skin, heart, blood vessels, and bone. However, achieving rapid crosslinking, strong wet adhesion and cohesion strengths, and minimal cytotoxicity remains a critical roadblock for clinical translation. Herein, in contrast to harsh and cytotoxic oxidants, magnesium oxide (MgO) particles were found to facilitate rapid crosslinking for injectable citrate-based mussel-inspired tissue bioadhesives synthesized by reacting citric acid, PEG-PPG-PEG diol and dopamine (iC-EPE). Our results confirmed the role of MgO particles as both crosslinkers and composite fillers to concurrently enhance bioadhesive cohesion and adhesion. iC-EPE crosslinked by MgO with/without sodium periodate (PI) exhibit enhanced mechanical strengths (1.0 Mpa < tensile strength ≤ 4.5 MPa) compared to that of iC-EPE crosslinked only by PI (~0.75 MPa), high adhesion strength (up to 125 kPa, 8 fold that of fibrin glue (~15 kPa)), tunable degradability (full degradation from <1 week to > 1 month), excellent in vitro and in vivo biocompatibility, encouraging anti-bacterial performance, and favorable wound closure efficacy. Thus, MgO crosslinked bioadhesives possess great potential for a wide range of applications in surgery and regenerative engineering.
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Bivalvos , Adhesivos Tisulares , Adhesivos , Animales , Citratos , Ácido Cítrico , Óxido de MagnesioRESUMEN
Leveraging the multifunctional nature of citrate in chemistry and inspired by its important role in biological tissues, a class of highly versatile and functional citrate-based materials (CBBs) has been developed via facile and cost-effective polycondensation. CBBs exhibiting tunable mechanical properties and degradation rates, together with excellent biocompatibility and processability, have been successfully applied in vitro and in vivo for applications ranging from soft to hard tissue regeneration, as well as for nanomedicine designs. We summarize in the review, chemistry considerations for CBBs design to tune polymer properties and to introduce functionality with a focus on the most recent advances, biological functions of citrate in native tissues with the new notion of degradation products as cell modulator highlighted, and the applications of CBBs in wound healing, nanomedicine, orthopedic, cardiovascular, nerve and bladder tissue engineering. Given the expansive evidence for citrate's potential in biology and biomaterial science outlined in this review, it is expected that citrate based materials will continue to play an important role in regenerative engineering.
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Materiales Biocompatibles/síntesis química , Ácido Cítrico/química , Ácido Cítrico/farmacología , Materiales Biomiméticos/química , Ácido Cítrico/sangre , Ácido Cítrico/líquido cefalorraquídeo , Química Clic , Humanos , Polímeros/síntesis química , Polímeros/química , Ingeniería de TejidosRESUMEN
Citrate based polymer poly(octamethylene citrate) (POC) has shown promise when formulated into composite material containing up to 65 wt% hydroxylapatite (HA) for orthopedic applications. Despite significant research into POC, insufficient information about the biocompatibility of the monomers 1,8-Octanediol and Citrate used in its synthesis is available. Herein, we investigated the acute cytotoxicity, immune response, and long-term functionality of both monomers. Our results showed a cell-type dependent cytotoxicity of the two monomers: 1,8-Octanediol induced less acute toxicity to 3T3 fibroblasts than Citrate while presenting comparable cytotoxicity to MG63 osteoblast-like cells; however, Citrate demonstrated enhanced compatibility with hMSCs compared to 1,8-Octanediol. The critical cytotoxic concentration values EC30 and EC50, standard for comparing cytotoxicity of chemicals, were also provided. Additionally, Citrate showed slower and less inhibitory effects on long-term hMSC cell proliferation compared with 1,8-Octanediol. Furthermore, osteogenic differentiation of hMSCs exposure to Citrate resulted in less inhibitory effect on alkaline phosphatase (ALP) production. Neither monomer triggered undesired pro-inflammatory responses. In combination with diffusion model analysis of monomer release from cylindrical implants, based on which the maximum concentration of monomers in contact with bone tissue was estimated to be 2.2 × 10-4 mmol/L, far lower than the critical cytotoxic concentrations as well as the 1,8-Octanediol concentration (0.4 mg/mL or 2.7 mmol/L) affecting hMSCs differentiation, we provide strong evidence for the cytocompatibility of the two monomers degraded from citrate-based composites in the orthopedic setting.
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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.
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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.
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Luminiscencia , Micelas , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Fagocitosis , Poliuretanos/química , Receptores de Neuropéptido Y/metabolismo , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Doxorrubicina/farmacología , Liberación de Fármacos , Humanos , Concentración de Iones de Hidrógeno , Ligandos , Células MCF-7 , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestructura , Ratones Desnudos , Péptidos/química , Fagocitosis/efectos de los fármacos , Análisis de Supervivencia , Células THP-1 , Factores de TiempoRESUMEN
Mitochondria serve as both "energy factories" and "suicide weapon stores" of cells. Targeted delivery of cytotoxic drugs to the mitochondria of tumor cells and tumor vascular cells is a promising strategy to improve the efficacy of chemotherapy. Here, multistage tumor-targeting liposomes containing two targeted peptide-modified lipids, cRGD-PEG2000-DSPE and KLA-PEG2000-DSPE, were developed for encapsulation of the anticancer drug paclitaxel (PTX, RGD-KLA/PTX-Lips). Compared with Taxol (free PTX), RGD/PTX-Lips and KLA/PTX-Lips, the half-maximal inhibitory concentration (IC50) value of RGD-KLA/PTX-Lips in vitro was 1.9-, 36.7- and 22.7-fold lower with 4T1 cells, respectively, because of higher levels of cellular uptake. Similar results were also observed with human umbilical vascular endothelial cells (HUVECs). An apoptosis assay showed that the total apoptotic ratio of RGD-KLA/PTX-Lips was the highest because of the mitochondria-targeted drug delivery and the activation of mitochondrial apoptosis pathways, as evidenced by visible mitochondrial localization, decreased mitochondrial membrane potential, release of cytochrome c and increased activities of caspase-9 and caspase-3. The strongest tumor growth inhibition (TGI; 80.6%) and antiangiogenesis effects without systemic toxicity were also observed in RGD-KLA/PTX-Lip-treated 4T1 tumor xenograft BALB/c mice. In conclusion, these multistage tumor-targeting liposomes represent a promising anticancer drug delivery system (DDS) capable of maximizing anticancer therapeutic efficacy and minimizing systemic toxicity.
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Liposomas/química , Neoplasias Mamarias Experimentales/patología , Paclitaxel/farmacología , Péptidos/química , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Células Cultivadas , Citocromos c/metabolismo , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular , Liposomas/administración & dosificación , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/metabolismo , Ratones , Ratones Endogámicos BALB C , Mitocondrias/metabolismo , Células 3T3 NIH , Paclitaxel/administración & dosificación , Fosfatidiletanolaminas/química , Polietilenglicoles/químicaRESUMEN
The field of tissue engineering and regenerative medicine relies heavily on materials capable of implantation without significant foreign body reactions and with the ability to promote tissue differentiation and regeneration. The field of bone tissue engineering in particular requires materials capable of providing enhanced mechanical properties and promoting osteogenic cell lineage commitment. While bone repair has long relied almost exclusively on inorganic, calcium phosphate ceramics such as hydroxyapatite and their composites or on non-degradable metals, the organically derived shell and pearl nacre generated by mollusks has emerged as a promising alternative. Nacre is a naturally occurring composite material composed of inorganic, calcium carbonate plates connected by a framework of organic molecules. Similar to mammalian bone, the highly organized microstructure of nacre endows the composite with superior mechanical properties while the organic phase contributes to significant bioactivity. Studies, both in vitro and in vivo, have demonstrated nacre's biocompatibility, biodegradability, and osteogenic potential, which are superior to pure inorganic minerals such as hydroxyapatite or non-degradable metals. Nacre can be used directly as a bulk implant or as part of a composite material when combined with polymers or other ceramics. While nacre has demonstrated its effectiveness in multiple cell culture and animal models, it remains a relatively underexplored biomaterial. This review introduces the formation, structure, and characteristics of nacre, and discusses the present and future uses of this biologically-derived material as a novel biomaterial for orthopedic and other tissue engineering applications. STATEMENT OF SIGNIFICANCE: Mussel derived nacre, a biological composite composed of mineralized calcium carbonate platelets and interplatelet protein components, has recently gained interest as a potential alternative ceramic material in orthopedic biomaterials, combining the integration and mechanical capabilities of calcium phosphates with increased bioactivity derived from proteins and biomolecules; however, there is limited awareness of this material's potential. Herein, we present, to our knowledge, the first comprehensive review of nacre as a biomaterial. Nacre is a highly promising yet overlooked biomaterial for orthopedic tissue engineering with great potential in a wide variety of material systems. It is our hope that publication of this article will lead to increased community awareness of the potential of nacre as a versatile, bioactive ceramic capable of improving bone tissue regeneration and will elicit increased research effort and innovation utilizing nacre.
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Materiales Biocompatibles/química , Sustitutos de Huesos/química , Ensayo de Materiales/métodos , Nácar/química , Animales , Materiales Biocompatibles/farmacología , Sustitutos de Huesos/farmacología , Huesos/metabolismo , Durapatita/química , Durapatita/farmacología , Humanos , Nácar/farmacologíaRESUMEN
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.
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Implantes Absorbibles , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Medios de Contraste/síntesis química , Técnicas de Diagnóstico Molecular/métodos , Nanocápsulas/química , Ultrasonografía/métodos , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Luminiscencia , Ratones , Ratones Endogámicos BALB C , Nanocápsulas/efectos de la radiación , Receptores de Neuropéptido Y , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Hernia repair is one of the most commonly performed surgical procedures worldwide, with a multi-billion dollar global market. Implant design remains a critical challenge for the successful repair and prevention of recurrent hernias, and despite significant progress, there is no ideal mesh for every surgery. This review summarizes the evolution of prostheses design toward successful hernia repair beginning with a description of the anatomy of the disease and the classifications of hernias. Next, the major milestones in implant design are discussed. Commonly encountered complications and strategies to minimize these adverse effects are described, followed by a thorough description of the implant characteristics necessary for successful repair. Finally, available implants are categorized and their advantages and limitations elucidated, including non-absorbable and absorbable (synthetic and biologically derived) prostheses, composite prostheses, and coated prostheses. This review not only summarizes the state of the art in hernia repair, but also suggests future research directions toward improved hernia repair utilizing novel materials and fabrication methods.
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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.
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Colorantes Fluorescentes , Ensayo de Materiales , Imagen Óptica/métodos , Poliglactina 910 , Animales , Femenino , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacocinética , Colorantes Fluorescentes/farmacología , Humanos , Poliglactina 910/química , Poliglactina 910/farmacocinética , Poliglactina 910/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
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.
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Antibacterianos/síntesis química , Antifúngicos/síntesis química , Bivalvos/química , Ácido Cítrico/química , Adhesivos Tisulares/química , Animales , Antibacterianos/farmacología , Antifúngicos/farmacología , Materiales Biocompatibles/química , Candida albicans/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Escherichia coli/efectos de los fármacos , Humanos , Hidrogeles , Espectroscopía de Resonancia Magnética , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Nanopartículas del Metal/química , Pruebas de Sensibilidad Microbiana , Plata/química , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus/efectos de los fármacos , Adhesivos Tisulares/farmacologíaRESUMEN
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 (â¼28 MPa) than that of normal PED (â¼8 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.
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Attempts to replicate native tissue architecture have led to the design of biomimetic scaffolds focused on improving functionality. In this study, biomimetic citrate-based poly (octanediol citrate)-click-hydroxyapatite (POC-Click-HA) scaffolds were developed to simultaneously replicate the compositional and architectural properties of native bone tissue while providing immediate structural support for large segmental defects following implantation. Biphasic scaffolds were fabricated with 70% internal phase porosity and various external phase porosities (between 5 and 50%) to mimic the bimodal distribution of cancellous and cortical bone, respectively. Biphasic POC-Click-HA scaffolds displayed compressive strengths up to 37.45 ± 3.83 MPa, which could be controlled through the external phase porosity. The biphasic scaffolds were also evaluated in vivo for the repair of 10-mm long segmental radial defects in rabbits and compared to scaffolds of uniform porosity as well as autologous bone grafts after 5, 10, and 15 weeks of implantation. The results showed that all POC-Click-HA scaffolds exhibited good biocompatibility and extensive osteointegration with host bone tissue. Biphasic scaffolds significantly enhanced new bone formation with higher bone densities in the initial stages after implantation. Biomechanical and histomorphometric analysis supported a similar outcome with biphasic scaffolds providing increased compression strength, interfacial bone ingrowth, and periosteal remodeling in early time points, but were comparable to all experimental groups after 15 weeks. These results confirm the ability of biphasic scaffold architectures to restore bone tissue and physiological functions in the early stages of recovery, and the potential of citrate-based biomaterials in orthopedic applications.