ABSTRACT
Immune evasion of Mycobacterium tuberculosis (Mtb) facilitates intracellular bacterial growth. The mechanisms of immune evasion, however, are still not fully understood. In this study, we reveal that tristetraprolin (TTP), one of the best characterized RNA-binding proteins controlling the stability of targeted mRNAs, mediates innate immune evasion of mycobacteria. We found that TTP knockout mice displayed reduced bacterial burden in the early stage after Mtb aerosol challenge. Macrophages deficient in TTP also showed an inhibition in intracellular mycobacterial growth. Live mycobacteria induced TTP protein expression in macrophages, which was blocked by the mTOR inhibitor rapamycin. Rapamycin and AZD8055 specifically blocked 4EBP1 phosphorylation in infected macrophages and suppressed intracellular BCG growth. Rapamycin promoted TTP protein degradation through the ubiquitination pathway, whereas the proteasome inhibitor MG-132 blocked rapamycin function and thus stabilized TTP protein. TTP induction suppressed the expression of iNOS/TNF-α/IL-12/IL-23, and weakened protective immune responses in macrophages, whereas rapamycin enhanced the bactericidal effects through TTP inhibition. Moreover, blocking TTP binding increased the expression of TNF-α and iNOS and suppressed intracellular mycobacterial growth. Overall, our study reveals a novel role for RNA-binding protein TTP in Mtb immune evasion mechanisms and provides a potential target for host-directed therapy against tuberculosis (TB).
ABSTRACT
Osteoinductive supplements without side effects stand out from the growth factors and drugs widely used in bone tissue engineering. Lithium magnesium sodium silicate hydrate (laponite) nanoflake is a promising bioactive component for bone regeneration, attributed to its inherent biosafety and effective osteoinductivity. Up to now, the in vivo osteogenic potential and mechanisms of laponite-encapsulated fibrous membranes remain largely unexplored. This study presents a unique method for homogeneously integrating high concentrations of laponite RDS into a polycaprolactone (PCL) matrix by dispersing laponite RDS sol into the polymer solution. Subsequently, a core-shell fibrous membrane (10RP-PG), embedding laponite-loaded PCL in its core, was crafted using coaxial electrospinning. The PCL core's slow degradation and the shell's gradient degradation enabled the sustained release of bioactive ions (Si and Mg) from laponite. In vivo studies on a critical-sized calvarial bone defect model demonstrated that the 10RP-PG membrane markedly enhanced bone formation and remodeling by accelerating the process of endochondral ossification. Further transcriptome analysis suggested that osteogenesis in the 10RP-PG membrane is driven by Mg and Si from endocytosed laponite, activating pathways related to ossification and endochondral ossification, including Hippo, Wnt and Notch. The fabricated nanocomposite fibrous membranes hold great promise in the fields of critical-sized bone defect repair.
ABSTRACT
Polymer-based scaffolds with different degradability have been investigated to screen the matrix whose degradation rate is more closely matched with the bone regeneration rate. However, these comparisons are inclined to be compromised by the animal individual differences. In this study, we constructed an integrated scaffold model comprising four parts with different degradability and bioactivity to achieve an in situ comparison of bone regeneration ability of different scaffolds. Slow-degradable polycaprolactone (PCL), fast-degradable poly (lactic-co-glycolic acid) (PLGA), and silica-coated PCL and PLGA scaffolds were assembled into a round sheet to form a hydroxyapatite (HA)-free integrated scaffold. HA-doped PCL, PLGA, and silica-coated PCL and PLGA scaffolds were assembled to create an HA-incorporated integrated scaffold. The in vivo experimental results demonstrated that the local acid microenvironment caused by the rapid degradation of PLGA interfered with the osteogenic process promoted by PCL-based scaffolds in defect areas implanted with HA-free integrated scaffolds. Since the incorporation of HA alleviated the acidic microenvironment to some extent, each scaffold in HA-incorporated scaffolds exhibited its expected bone regeneration capacity. Consequently, it is feasible to construct an integrated structure for comparing the osteogenic effects of various scaffolds in situ, when there is no mutual interference between the materials. The strategy presented in this study inspired the structure design of biomaterials to enable in situ comparison of bone regeneration capacity of scaffolds.
Subject(s)
Durapatite , Osteogenesis , Polyesters , Polylactic Acid-Polyglycolic Acid Copolymer , Tissue Scaffolds , Tissue Scaffolds/chemistry , Osteogenesis/drug effects , Animals , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polyesters/chemistry , Durapatite/chemistry , Bone Regeneration/drug effects , Polymers/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Polyglycolic Acid/chemistry , Tissue Engineering/methods , Lactic Acid/chemistryABSTRACT
With the increasing application of lithium-ion batteries, the demand for high energy density, high-rate performance and high stability lithium-ion batteries is becoming more and more urgent. Ti2CO2 MXene, as a two-dimensional material with multilayer atomic structure and multiple active sites, has great advantages in lithium-ion battery electrode materials. However, the original Ti2CO2 MXene has been unable to meet the requirements of lithium-ion batteries due to its semiconductor properties. Doping is an effective means to regulate the conductivity and electrochemical properties of Ti2CO2 and improve the capacity of lithium-ion batteries and other energy storage devices. Hence, we use first-principles calculations to study the effect of V atom doping on the adsorption and diffusion of Li on the MXene surface. The density of states (DOS) and partial density of states (PDOS) of TiVCO2 and Ti2CO2 MXene indicated the transition of their conductive types from semiconductors to conductors. In addition, we observed that TiVCO2 has higher electrical conductivity and ion transport speed than the original Ti2CO2 MXene, and at the same time, Li atoms can be adsorbed well on the surface of MXene and show a lower diffusion energy barrier. Therefore, TiVCO2 is expected to become the anode material for the next generation of lithium-ion batteries and has good lithium storage performance.
ABSTRACT
Effective tissue repair relies on the orchestration of different macrophage phenotypes, both the M2 phenotype (promotes tissue repair) and M1 phenotype (pro-inflammatory) deserve attention. In this study, we propose a sequential immune activation strategy to mediate bone regeneration, by loading lipopolysaccharide (LPS) onto the surface of a strontium (Sr) ions -contained composite scaffold, which was fabricated by combining Sr-doped micro/nano-hydroxyapatite (HA) and dual degradable matrices of polycaprolactone (PCL) and poly (lactic-co-glycolic acid) (PLGA). Our strategy involves the sequential release of LPS to promote macrophage homing and induce the expression of the pro-inflammatory M1 phenotype, followed by the release of Sr ions to suppress inflammation. In vitro and in vivo experiments demonstrated that, the appropriate pro-inflammatory effects at the initial stage of implantation, along with the anti-inflammatory effects at the later stage, as well as the structural stability of the scaffolds conferred by the composition, can synergistically promote the regeneration and repair of bone defects.
ABSTRACT
Due to the decomposition temperature of Polyamide 66 (PA66) in the environment is close to its thermoforming temperature, it is difficult to construct porous scaffolds of PA66/nanohydroxyapatite (PA66/HAp) by fused deposition modeling (FDM) three-dimensional (3D) printing. In this study, we demonstrated for the first time a method for 3D printing PA66/HAp composites at room temperature, prepared PA66/HAp printing ink using a mixed solvent of formic acid/dichloromethane (FA/DCM), and constructed a series of composite scaffolds with varying HAp content. This printing system can print composite materials with a high HAp content of 60 wt %, which is close to the mineral content in natural bone. The physicochemical evaluation presented that the hydroxyapatite was uniformly distributed within the PA66 matrix, and the PA66/HAp composite scaffold with 30 wt % HAp content exhibited optimal mechanical properties and printability. The results of in vitro cell culture experiments indicated that the incorporation of HAp into the PA66 matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs) cultured on the scaffold. In vivo animal experiments suggested that the PA66/HAp composite material with 30 wt % HAp content had the best structural maintenance and osteogenic performance. The three-dimensional PA66/HAp composite scaffold prepared by low temperature printing in the current study holds great potential for the repair of large-area bone defects.
Subject(s)
Durapatite , Mesenchymal Stem Cells , Nylons , Printing, Three-Dimensional , Tissue Scaffolds , Durapatite/chemistry , Tissue Scaffolds/chemistry , Nylons/chemistry , Animals , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Bone Regeneration/drug effects , Osteogenesis/drug effects , Tissue Engineering/methods , Cell Proliferation/drug effects , Cell Differentiation/drug effects , Temperature , Cell AdhesionABSTRACT
Prussian blue analogs (PBAs) show great promise as anode materials for potassium-ion batteries (PIBs) due to their high specific capacity. However, PBAs still suffer from the drawbacks of low electronic conductivity and poor structural stability, leading to inadequate rate and cyclic performance. To address these limitations, CoFe PBA nanocubes wrapped with N/S doped carbon network (CoFe PBA@NSC) as anode for PIBs is designed by using thermal-induced in situ conversion strategy. As expected, the structural advantages of nanosized PBA cubes, such as abundant interfaces and large surface area, enable the CoFe PBA@NSC electrode to demonstrate superior rate properties (557 and 131 mAh g-1 at 0.05 and 10 A g-1) and low capacity degradation (0.093% per cycle over 1000 cycles at 0.5 A g-1). Furthermore, several ex situ characterizations revealed the K-ion storage mechanism. Fe+ and Co0 are generated during potassicization, followed by a completely reversible chemical state of iron while some cobalt monomers remained during depotassication. Additionally, the as-built potassium-ion hybrid capacitor based on CoFe PBA@NSC anode exhibits a high energy density of 118 Wh kg-1. This work presents an alternative but promising synthesis route for Prussian blue analogs, which is significant for the advancement of PIBs and other related energy storage devices.
ABSTRACT
The combined design of scaffold structure and multi-biological factors is a prominent strategy to promote bone regeneration. Herein, a composite scaffold of mesoporous hydroxyapatite (HA) microspheres loaded with the bone morphogenetic protein-2 (BMP-2) and a poly(DL-lactic-co-glycolic acid) (PLGA) matrix is constructed by 3D printing. Furthermore, the chemokine stromal cell-derived factor-1α (SDF-1α) is adsorbed on a scaffold surface to achieve the sequential release of the dual-biofactors. The results indicate that the rapid release of SDF-1α chemokine on the scaffold surface effectively recruits bone marrow-derived mesenchymal stem cells (BMSCs) to the target defect area, whereas the long-term sustained release of BMP-2 from the HA microspheres in the degradable PLGA matrix successfully triggers the osteogenic differentiation in the recruited BMSCs, significantly promoting bone regeneration and reconstruction. In addition, these structures/biofactors specially combining scaffold exhibit significantly better biological performance than that of other combined scaffolds, including the bare HA/PLGA scaffold, the scaffold loaded with SDF-1α or BMP-2 biofactor alone, and the scaffold with surface SDF-1α and BMP-2 dual-biofactors. The utilization of mesoporous HA, the assembly method, and sequential release of the two biofactors in the 3D printed composite scaffold present a new method for future design of high-performance bone repairing scaffolds.
Subject(s)
Durapatite , Osteogenesis , Durapatite/pharmacology , Durapatite/chemistry , Microspheres , Tissue Scaffolds/chemistry , Chemokine CXCL12/pharmacology , Lactic Acid/chemistry , Bone RegenerationABSTRACT
Bone tissue engineering scaffolds with similar composition, structure, and mechanical properties to natural bone are conducive to bone regeneration. The objective of this study was to prepare hydroxyapatite/poly (lactic-co-glycolic acid) (HA/PLGA) three-dimensional porous scaffolds with HA content close to natural bone and strong mechanical strength to promote osteogenesis. To achieve this, we modified HA microspheres with polyvinyl alcohol to create an inorganic filler to endow the HA/PLGA printing ink with higher HA content and excellent printing fluidity for 3D printing. We successfully printed a series of HA/PLGA scaffolds with different HA contents. The highest HA content reached 60 wt%, which is close to the mineral percentage in natural bone. The composition, structure, mechanical properties, and in vitro degradability of the fabricated scaffolds were systematically characterized. The cytocompatibility and osteogenic activity of the fabricated HA/PLGA scaffolds were evaluated by in vitro cell culture and rabbit femoral defect repair experiments in vivo. The results indicated that the HA/PLGA composite scaffold with 45 wt% HA had the highest compressive strength of more than 40 MPa, which was six times higher than that of the pure PLGA scaffold. The incorporation of HA microspheres into the PLGA matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stem cells (BMSCs) cultured on the surface of the scaffolds. Animal experiments showed that the HA/PLGA composite with 45 wt% HA exhibited the best structure maintenance and osteogenic performance in vivo. The prepared HA/PLGA composite 3D scaffold with HA microsphere reinforcement has considerable application potential in the field of large bone defect repair.
Subject(s)
Durapatite , Osteogenesis , Animals , Bone Regeneration , Durapatite/pharmacology , Microspheres , Printing, Three-Dimensional , RabbitsABSTRACT
With the global outbreak of coronavirus disease 2019 (COVID-19), public health has received unprecedented attention. The cultivation of emergency and compound professionals is the general trend through public health education. However, current public health education is limited to traditional teaching models that struggle to balance theory and practice. Fortunately, the development of artificial intelligence (AI) has entered the stage of intelligent cognition. The introduction of AI in education has opened a new era of computer-assisted education, which brought new possibilities for teaching and learning in public health education. AI-based on big data not only provides abundant resources for public health research and management but also brings convenience for students to obtain public health data and information, which is conducive to the construction of introductory professional courses for students. In this review, we elaborated on the current status and limitations of public health education, summarized the application of AI in public health practice, and further proposed a framework for how to integrate AI into public health education curriculum. With the rapid technological advancements, we believe that AI will revolutionize the education paradigm of public health and help respond to public health emergencies.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Artificial Intelligence , Curriculum , Health EducationABSTRACT
BACKGROUND: Transbronchial cryobiopsy (TBCB), a novel way of obtaining a specimen of lung tissue using a flexible cryoprobe, can obtain large lung biopsies without crush artifacts. The freezing time of TBCB was empirically selected from 3 to 7 s in the previous studies. However, no consensus has yet been reached regarding the optimal freezing time used in TBCB. OBJECTIVES: The primary endpoint was biopsy size in different freezing times. The secondary endpoints included sample histological quality, diagnostic confidence, and complications in different freezing times. METHODS: Patients who were suspected of DPLD requiring histopathological examination for further evaluation were enrolled in this study. Distinct biopsies were obtained by using different freezing times increased from 3 to 6 s sequentially. Samples were reviewed by 2 external expert pathologists. RESULTS: A total of 33 patients were enrolled, and 143 transbronchial cryobiopsies were taken in this trial. An average of 4.33 samples were taken from each patient. The mean biopsy size of different freezing times from 3 to 6 s was 9.10 ± 4.37, 13.23 ± 5.83, 16.26 ± 5.67, and 18.83 ± 7.50 mm2, respectively. A strong correlation between freezing time and biopsy size was observed (r = 0.99, p < 0.01). Statistically significant difference of biopsy size was detected in the freezing time of 3 s versus 4 s (p < 0.01) and 4 s versus 5 s (p = 0.02), but not in the freezing time of 5 s versus 6 s (p = 0.10). Overall bleeding in different freezing times from 3 to 6 s was 53.33%, 67.50%, 89.47%, and 77.14%, respectively. A significantly higher overall bleeding was observed when the freezing time exceeded 4 s (RR = 1.67, p < 0.01). Pneumothorax occurred in 4 cases (12.12%). One lethal case (3.03%) was noted 25 days after TBCB. Lung parenchyma was preserved well in all cryobiopsy samples. Thirty-one (93.94%) patients' histopathological findings were identified as sufficient to establish a CRP diagnosis. There was no statistical difference in diagnostic confidence between different freezing times. CONCLUSION: A longer freezing time was associated with a larger size of the biopsy sample but a higher risk of bleeding. The optimal transbronchial cryobiopsy freezing time is 3-4 s, which is easily achievable and provides an adequate biopsy size whilst creating a safety threshold from complications.
Subject(s)
Bronchoscopy , Lung , Biopsy/adverse effects , Bronchoscopy/adverse effects , Freezing , Hemorrhage , Humans , Incidence , Lung/pathology , Prospective StudiesABSTRACT
The deformation shrinkage of a poly(lactide-co-glycolide) (PLGA) fibrous material seriously affects its biomedical application. To demonstrate the underlying shrinking mechanism and to find a method to prevent the shrinkage of an electrospun PLGA membrane, we investigated the shrinking behavior of PLGA electrospun membranes under various test conditions and discussed the underlying shrinking mechanism. The results indicated that the shrinkage of the electrospun PLGA membrane was mainly regulated by the glass transition of its polymer fiber; the temperature and liquid environment were found to be the two main factors leading to the shrinkage of the electrospun PLGA membrane through affecting its glass transition. Then a heat stretching (HS) technique was proposed by us to stabilize the electrospun PLGA membrane. After HS treatment, the glass transition temperature (Tg) of the electrospun PLGA membrane could increase from 48.38 °C to 54.55 °C. Our results indicated that the HS-treated membranes could maintain a high area percentage of 90.89 ± 2.27% and 84.78 ± 3.36% after immersion respectively in PBS and blood at 37 °C for 2 hours. Further experiments confirmed that the HS technique could also stabilize the dimensional structure of the electrospun PDLLA membrane in PBS and blood at 37 °C. This study provides an effective strategy for preventing the shrinkage of electrospun polyester biomaterials in a physiological environment that may benefit both the material structural stability and the in vivo biological performance.
Subject(s)
Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Animals , Dimethylformamide/chemistry , Glass/chemistry , Methylene Chloride/blood , Methylene Chloride/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/blood , Rats , Temperature , Tensile StrengthABSTRACT
The ideal scaffold for bone repair should have a hierarchical pore structure and gradient degradation performance to satisfy the uniform adhesion and proliferation of cells in the scaffold at the early stage of implantation, as well as providing space for the subsequent regeneration of bone tissue. To this end, we developed a hierarchical polylactic acid glycolic acid copolymer (PLGA)/nano-hydroxyapatite (n-HA)/gelatin (Gel) (PHG) scaffold with a printed PLGA/n-HA (PH) framework and a Gel network filler for bone regeneration by the combination of 3D printing and freeze-drying technologies. The fabricated PHG scaffold features large front hole size (>1100 µm × 1100 µm) and side hole size (>500 µm) to provide sufficient open space and reliable integrated support for cell and tissue ingrowth. The gelatin network filled in the PH framework played the role of a cell holder just like an extracellular matrix (ECM) in the early stage. In vitro degradation experiments revealed that the gelatin network completely degraded within 5 weeks while the structural integrity of the framework still remained at the 32nd week. The results of cell culture confirmed that the PHG scaffold was more conducive to cell attachment. In vivo assessments in a rat femoral defect model showed that PHG scaffolds were more favored for new bone formation and achieving a tighter bond between the scaffold and the original tissues. The hierarchical PHG scaffold has great application potential in bone tissue engineering and will provide a reference for the model design of bone scaffolds.
Subject(s)
Bone Regeneration , Durapatite/chemistry , Extracellular Matrix/metabolism , Printing, Three-Dimensional , Tissue Scaffolds , Cell Adhesion , Polylactic Acid-Polyglycolic Acid CopolymerABSTRACT
Doxorubicin (Dox)-loaded or selenium-substituted hydroxyapatite (HA) has been developed to achieve anti-osteosarcoma or bone regeneration in a number of studies. However, currently, there is a lack of studies on the combination of Dox and selenium loading in/on HA and comparative research studies on which form and size of HA are more suitable for drug loading and release in the treatment osteogenesis after osteosarcoma resection. Herein, selenium-doped rod-shaped nano-HA (n-HA) and spherical mesoporous HA (m-HA) were successfully prepared. The doping efficiency of selenium and the Dox loading capacity of selenium-doped HA with different morphologies were studied. The release kinetics of Dox and the selenium element in phosphate-buffered saline with different pH values was also comparatively investigated. The drug loading results showed that n-HA exhibited 3 times higher selenium doping amount than m-HA, and the Dox entrapment efficiency of selenium-doped n-HA (0.1Se-n-HA) presented 20% higher than that of selenium-doped m-HA (0.1Se-m-HA). The Dox release behaviors of HA in two different morphologies showed similar release kinetics, with almost the same Dox releasing ratio but slightly more Dox releasing amount in selenium-doped HA than in HA without selenium. The selenium release from selenium-doped n-HA-D (0.1Se-n-HA-D) particles was 2 times as much as that of selenium-doped m-HA-D (0.1Se-m-HA) particles. Our study indicated that n-HA loaded with Dox and selenium may be a promising drug delivery strategy for inhibition of osteosarcoma recurrence and promoting osteogenesis simultaneously.
ABSTRACT
BACKGROUND: The recurrence of positive SARS-CoV-2 RT-PCR is frequently found in discharged COVID-19 patients but its clinical significance remains unclear. The potential cause, clinical characteristics and infectiousness of the recurrent positive RT-PCR patients need to be answered. METHODS: A single-centered, retrospective study of 51 discharged COVID-19 patients was carried out at a designated hospital for COVID-19. The demographic data, clinical records and laboratory findings of 25 patients with recurrent positive RT-PCR from hospitalization to follow-up were collected and compared to 26 patients with negative RT-PCR discharged regularly during the same period. Discharged patients' family members and close contacts were also interviewed by telephone to evaluate patients' potential infectiousness. RESULTS: The titer of both IgG and IgM antibodies was significantly lower (p = 0.027, p = 0.011) in patients with recurrent positive RT-PCR. Median duration of viral shedding significantly prolonged in patients with recurrent positive RT-PCR (36.0 days vs 9.0 days, p = 0.000). There was no significant difference in demographic features, clinical features, lymphocyte subsets count and inflammatory cytokines levels between the two groups of patients. No fatal case was noted in two groups. As of the last day of follow-up, none of the discharged patients' family members or close contact developed any symptoms of COVID-19. CONCLUSIONS: Patients with low levels of IgG and IgM are more likely to have recurrent positive SARS-CoV-2 RT-PCR results and lead to a prolonged viral shedding. The recurrent positive of SARS-CoV-2 RT-PCR may not indicate the recurrence or aggravation of COVID-19. The detection of SARS-CoV-2 by RT-PCR in the patients recovered from COVID-19 is not necessarily correlated with the ability of transmission.
Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , RNA, Viral/genetics , Reinfection/virology , SARS-CoV-2/isolation & purification , Adult , COVID-19/blood , COVID-19/immunology , Case-Control Studies , China , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Patient Discharge , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Time Factors , Virus SheddingABSTRACT
To guide sustainable development in the hospitality industry requires hotel staff engagement, so what causes and how to facilitate the implementation of low-carbon behaviors should be high priorities. However, most prior studies focused on hotel guest behavior or discussed, on an individual level, the psychological aspects of the factors of the low-carbon behavior of either managers or employees. Therefore, this research aims to examine the effect of influencing factors inside and outside of the hotel context on hotel staff's low-carbon behaviors in star-rated hotels. A set of influencing factors were identified by using literature retrieval, ground theory and in-depth interviews. Structural equation modelling was then applied with 440 valid questionnaires collected from representative star-rated hotels in Eastern China. The results revealed that low-carbon managerial activities, strategic orientation, social norms, and perceived behavior control were four key factors affecting the low-carbon behavior adoption of staff from star-rated hotels. Among them, low-carbon managerial activities were found to be the strongest factor affecting hotel staff's low-carbon behaviors. Consumer attitude, however, exerted no significant impact. Targeted strategies were finally proposed for the improvement of hotel staff's low-carbon behavior from the perspectives of hoteliers and governments. This study contributes to the generation mechanism of low-carbon behavior among staff and, in practice, towards behavioral improvement by providing comprehensive insights about the attribution of factors belonging to multiple dimensions related to the low-carbon behavior of staff in the hotel industry.
Subject(s)
Carbon , Industry , China , Commerce , Conservation of Natural Resources , Empirical Research , Female , Humans , MaleABSTRACT
Attributed to their structure and composition manipulated to mimic natural bone tissue, porous scaffolds composed of inorganic nano-hydroxyapatite (n-HA) and organic polymers with different degrees of degradability have been proven to be a promising bone regeneration strategy. However, long-term and in-depth comparative research on the effects of scaffolds with different matrices and degrees of degradability on bone reconstruction is still lacking. In this study, the ultralong-term osteogenic performance of three polymeric composite scaffolds based on non-degradable polyamide 66 (PA66), slowly degradable polycaprolactone (PCL) and fast degradable poly (lactic-co-glycolic acid) (PLGA) were investigated comparatively after implanting the scaffolds into rabbit femoral defects for 12, 15, 18 and 21 months. The results demonstrated that the structural integrity of the scaffolds played a positive role in long-term bone reconstruction. Thus the n-HA/PA66 and n-HA/PCL scaffolds have a higher relative bone volume and bone density than the n-HA/PLGA scaffolds from 12 to 21 months. In addition, the favorable surface wettability and collagen-like molecular structure should endow the n-HA/PA66 scaffold with the best long-term osteogenic property among the three scaffolds. The ultralong-term comparative study reveals that a relatively stable scaffold integrity, together with favorable matrix molecular characteristics and hydrophilicity, may be more important for long-term osteogenesis besides the effect of scaffold pore structure, rather than the pursuit of fast scaffold degradation. The results also show that the space left by scaffold degradation is not easily occupied by new bone tissue, especially after bone tissue has formed a stable structure or the bone interface has become inert.
Subject(s)
Biocompatible Materials/chemistry , Nylons/chemistry , Polyesters/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Tissue Scaffolds/chemistry , Animals , Femur/injuries , Femur/pathology , Femur/physiology , Femur/surgery , Osteogenesis , RabbitsABSTRACT
A novel bilayer fibrous membrane for guided tissue regeneration (GTR) was prepared via two-step electrospinning process, subsequent crosslinking and surface conjugation with heparin. The bilayer membrane consists of upper layer polycaprolactone/gelatin (PCL/Gel) membrane for soft tissue regeneration and lower layer PCL/Gel/nano-hydroxyapatite (PCL/Gel/n-HA) membrane for hard tissue regeneration. The results indicated that the physicochemical and biological properties of the membrane were strongly influenced by the crosslinking time and by the heparin conjugation. Crosslinking effectively prolonged the degradation time while maintaining the membrane barrier function, and the surface heparin conjugation obviously improved the biological performance of the membrane. An enhanced cell adhesion and proliferation were observed on the heparin-conjugated fibrous membranes, which also showed good histocompatibility and favorable in vivo degradability. The electrospun bilayer fibrous membrane may have promising prospect for modulation of cell response and simultaneous regeneration of soft and hard tissues.