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Research on essential performance of oxidized chitosan-crosslinked acellular porcine aorta modified with bioactive SCPP/DOPA for esophageal scaffold with enhanced mechanical strength, biocompatibility and anti-inflammatory

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Abstract

Acellular porcine aorta (APA) is an excellent candidate for an implanted scaffold but needs to be modified with appropriate cross-linking agent to increase its mechanical property and storage time in vitro as well as to give itself some bioactivities and eliminate its antigenicity for acting as a novel esophageal prosthesis. In this paper, a polysaccharide crosslinker (oxidized chitosan, OCS) was prepared by oxidizing chitosan using NaIO4 and further used to fix APA to prepare a novel esophageal prosthesis (scaffold). And then the surface modification with dopamine (DOPA) and strontium-doped calcium polyphosphate (SCPP) were performed one after another to prepare DOPA/OCS-APA and SCPP-DOPA/OCS-APA to improve the biocompatibility and inhibit inflammation of the scaffolds. The results showed that the OCS with a feeding ratio of 1.5:1.0 and a reaction time of 24 h had a suitable molecular weight and oxidation degree, almost no cytotoxicity and good cross-linking effect. Compared with glutaraldehyde (GA) and genipin (GP), OCS-fixed APA could provide a more suitable microenvironment for cell proliferation. The vital cross-linking characteristics and cytocompatibility of SCPP-DOPA/OCS-APA were evaluated. Results suggested that SCPP-DOPA/OCS-APA exhibited suitable mechanical properties, excellent resistance to enzymatic degradation/acid degradation, suitable hydrophilicity, and the ability to promote the proliferation of Human normal esophageal epithelial cells (HEECs) and inhibit inflammation in vitro. In vivo tests also confirmed that SCPP-DOPA/OCS-APA could diminish the immunological response to samples and had a positive impact on bioactivity and anti-inflammatory. In conclusion, SCPP-DOPA/OCS-APA could act as an effective, bioactive artificial esophageal scaffold and be expected to be used for clinical in the future.

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Bovine pericardium(BP)is one of the biological membranes with extensive application in tissue engineering. To fully investigate the potential clinical applications of this natural biological material, a suitable cross-linking reagent is hopefully adopted for modification. Glutaraldehyde (GA) is a clinically most common synthetic cross-linking reagent. In the study, oxidized hyaluronic acid (AHA) was developed to substitute GA to fix acellular bovine pericardium (ABP) for lower cytotoxicity, aiming to evaluate the feasibility of AHA as a cross-linking reagent and develop AHA-fixed ABP as a biological patch for abdominal wall repair. The AHA with the feeding ratio (1.8:1.0) has an appropriate molecular weight and oxidation degree, almost no cytotoxicity and good cross-linking effect. The critical cross-linking characteristics and cytocompatibility of AHA-fixed ABP were also investigated. The results demonstrated that 2.0% AHA-fixed ABP had the most suitable mechanical properties, thermal stability, resistance to enzymatic degradation and hydrophilicity. Moreover, 2.0% AHA-fixed samples exhibited an excellent cytocompatibility with human peritoneal mesothelial cells (HPMC) and low antigenicity. It also showed a prominent anti-calcification ability required for abdominal wall repair. Our data provided experimental basis for future research on AHA as a new cross-linking reagent and AHA-fixed ABP for abdominal wall repair.
Article
Vascularized bone tissue engineering is regarded as one of the optimal treatment options for large bone defects. The lack of angiogenic properties and unsatisfactory physicochemical performance restricts calcium phosphate cement (CPC) from application in vascularized bone tissue engineering. Our previous studies have developed a starch and BaSO4 incorporated calcium phosphate hybrid cement (CPHC) with improved mechanical strength and handling properties. However, the bioactivity-especially the angiogenic ability-is still absent and requires further improvement. Herein, based on the reported CPHC and the osteogenic and angiogenic properties of strontium (Sr) ions, a strontium-enhanced calcium phosphate hybrid cement (Sr-CPHC) was developed to improve both biological and physicochemical properties of CPC. Compared to CPC, the initial setting time of Sr-CPHC was prolonged from 2.2 min to 20.7 min. The compressive strength of Sr-CPHC improved from 11.21 MPa to 45.52 MPa compared with CPC as well. Sr-CPHC was biocompatible and showed promotion of alkaline phosphatase (ALP) activity, calcium nodule formation and osteogenic relative gene expression, suggesting high osteogenic-inductivity. Sr-CPHC also facilitated the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro and up-regulated the expression of the vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1). In vivo evaluation showed marked new bone formation in a rat calvarial defect model with Sr-CPHC implanted. Sr-CPHC also exhibited enhancement of neovascularization in subcutaneous connective tissue in a rat subcutaneous implantation model. Thus, the Sr-CPHC with the dual effects of osteogenesis and angiogenesis shows great potential for clinical applications such as the repair of ischemic osteonecrosis and critical-size bone defects.
Article
Tissue repair can be induced subsequently by the early inflammatory response after biomaterial implantation. However, the accomplishment of late regeneration process requires inhibit inflammation. This study aims to realize the gradient regulation of osteogenic immune micro-environment regenerating lost bone tissues by utilizing the synergistic effect of chitooligosaccharides (COS) and inorganic ions. Zinc (Zn)-Calcium (Ca)-Strontium (Sr) doped mesoporous silica nanoparticles (MSN) (denoted as MSNion) was successfully produced by cetyltrimethylammonium-bromide-mediated template method and its phase, morphology, structure, physicochemical properties, in vitro degradability were studied here. Results indicated that Si⁴⁺, Zn²⁺, Ca²⁺ and Sr²⁺ were incorporated into MSN and significant improvement can be viewed on the degradation performance of MSNion. COS was successfully loaded into MSNion (MSNion-COS), and the ability to gradient regulation of osteo-immune environment was investigated. Noticeably, the inflammatory cell was activated by MSNion-COS in early stage because of ions release, showing the pro-inflammatory property. In the latter stage, we can clearly observe the anti-inflammatory property of the MSNion-COS with upregulating the anti-inflammatory cytokines secretion, which further activated the osteogenic differentiation. Specifically, osteogenesis-related genes (Alkaline phosphatase (ALP), Osteocalcin (OCN), Osterix (OSX), and runt-related transcription factor 2 (RUNX2)) and the degree of calcium deposition of bone marrow mesenchymal stem cells (BMSCs) were significantly upregulated in the later anti-inflammation environment of macrophages modulated by MSNion-COS. Results suggested that MSNion-COS fully demonstrated the gradient regulation of osteo-immune environment, benefiting for accelerating osteogenesis.
Article
This review focuses on vascularization and strategies involved in its evaluation and modulation. Clinical issues associated with engineered tissues of an atomically relevant size that require a vascular network to supply their cells with nutrients and oxygen are analyzed in terms of vascular network formation within scaffolds, which can be produced from varying biomaterials, with the capability of connecting to the vasculature of the patient. Developing angiogenesis techniques and monitoring of angiogenesis development as well as how these methods can be further utilized to tailor vascularization within large tissue engineered constructs are also discussed. Finally, we offer a glimpse toward the future by providing an outlook for vascularization and associated emerging bioprinting concepts in tissue engineering applications.
Article
Silk fibroin (SF) is increasingly needed in tissue engineering for its superior biocompatibility. However, the practical applications of pure SF biomaterials confront bacterial infection problems. In this study, chitosan (CS) and polydopamine (PDA) were introduced into electrospun nanofibrous SF mats through layer-by-layer self-assembly (LBL) to obtain enhanced antibacterial ability and cytocompatibility. The surface morphology and composition analysis confirmed the successful deposition. After depositing 15 bilayers, the tensile modulus of the mats in wet condition increased from 2.16 MPa (pristine SF mats) to 4.89 MPa. A trend towards better hydrophilicity performance was also recorded with more bilayers coating on the mats. Besides, LBL structured mats showed improved antibacterial ability of more than 98 % against E. coli and S. aureus. In addition, advancement in biocompatibility was observed during the proliferation experiment of L929 cells. Overall, the deposition of CS and PDA may further expand the use of SF in biomedical field.
Article
Biomaterials are a cornerstone technology of the biomedical device, tissue engineering, and regenerative medicine industries. While traditional biomaterials are fully defined synthetics, growing evidence supports the use of extracellular matrix-based biomaterials produced through the decellularization of organs, tissues, or cell cultures. These materials are particularly advantageous as they largely retain the structure and the biochemical nature of the original tissue, properties that are often difficult to reproduce with synthetics. Indeed, there are many FDA-approved and clinically used extracellular matrix-based materials that are generated through decellularization processes. In this review, we first describe methods of decellularization used to produce these materials and their associated advantages and limitations, discuss the current use of extracellular matrix-based materials in regenerative engineering applications, describe the areas where current research is occurring, and forecast areas where impactful research may appear. The regeneration of tissues often requires a scaffold material to support and guide the cells that are performing the repair. Often, these materials are manmade and lack many of the key features present in native tissue. However, a tissue can be processed to remove its cells (a process called decellularization), leaving behind a scaffold of proteins and polysaccharides known as the extracellular matrix. These decellularized matrices are attractive scaffolds for use in regenerative medicine applications, and they are the subject of this review.
Article
Hydrogel can provide a favorable moisture environment for skin wound healing. In this study, a novel in-situ crosslinked injectable hydrogel was prepared using the water-soluble amidated pectin (AP) and oxidized chitosan (OC) through Schiff-base reaction without any chemical crosslinker. The influence of AP content on the properties of the hydrogel was systemically investigated. It showed that gelation time, pore structure, swelling capability and degradability of the hydrogel can be tuned by varying the content of amine and aldehyde groups from AP and OC. All the porous hydrogels with various AP contents (65%, 70%, and 80%) presented desirable gelation time, swelling property, high hemocompatibility and biocompatibility. Particularly, AP-OC-65 hydrogel presented superior swelling capability and better hemo- and bio-compatibility, owing to more residual amine sites in the hydrogel. Therefore, the injectable AP-OC-65 hydrogel has a greater potential for application to wound dressing or skin substitute.
Article
Chitosan is an antimicrobial, biodegradable and biocompatible natural polymer, commercially derived from the partial deacetylation of chitin. Currently modified chitosan has occupied a major part of scientific research. Modified chitosan has excellent biotic characteristics like biodegradation, antibacterial, immunological, metal-binding and metal adsorption capacity and wound-healing ability. Chitosan is an excellent candidate for drug delivery, food packaging and wastewater treatment and is also used as a supporting object for cell culture, gene delivery and tissue engineering. Modification of pure chitosan via grafting improves the native properties of chitosan. Chitosan grafted copolymers exhibit high significance and are extensively used in numerous fields. In this review, modifications of chitosan through several graft copolymerization techniques such as free radical, radiation, and enzymatic were reported and the properties of grafted chitosan were discussed. This review also discussed the applications of grafted chitosan in the fields of drug delivery, food packaging, antimicrobial, and metal adsorption as well as dye removal.
Article
Chitosan has fascinating antibacterial activity, good biodegradation, outstanding biocompatibility, non-toxicity and excellent physical and chemical properties. As a result, chitosan has been widely used in the field of antibacterial. Chitosan and its derivatives show antibacterial activity against fungi, gram-positive bacteria and gram-negative bacteria. In recent years, there have been some reviews about the antibacterial activity of chitosan and its derivatives. This review adds many valuable concerns on the basis of those previous reviews. For example, composite of chitosan and metal, composite of chitosan and metal oxide, etc. This review will systematically analyze various influencing factors of chitosan, so as to clearly summarize the antibacterial mechanism of chitosan. Finally, the challenges and prospects of chitosan-based materials as antimicrobial agents are assessed and commented.
Article
Traditional CPC cements have attracted wide attentions in repairing bone defects for injectability, easy plasticity and good osseointegration. However, its further application was limited by poor mechanical properties, long setting time and unsatisfactory biocompatibility. To solve these problems, polydopamine (DOPA) coated strontium-doped calcium polyphosphate (SCPP) fibers were added into CPC cements for the first time. A doping amount at fiber weight fraction of 0%, 1%, 2% and 5% was designed to develop a multifunctional composite fitting for bone tissues' regeneration and reconstruction and the optimum amount was selected through subsequent physicochemical and biological characterizations. The results implied DOPA coating successfully formed stable connections between SCPP fibers and CPC matrix, which simultaneously reinforced biomechanical strength and tenacity (5% SCPP/D/CPC samples exhibited more prominent mechanical property than others). In addition, 5% D/SCPP fibers doped composite cements were characterized as markedly-improved cytocompatibility: Sr2+ introduction induced cytoactive and significantly accelerated proliferation, attachment and spreading of osteoblasts. Besides, it also stimulated the secretion of OT, Col-I and ALP from seeded MG63, which was a critical character for further inducing osteogenic process, mineralization and bone tissues formation. The promoted cytocompatibility and improved osteogenesis-related growth factors' secretion could be attributed to constant and controllable release of Sr2+ and this deduction was approved by ICP analysis. In addition, Sr doping made this novel cement had a potential efficacy to inhibit aseptic loosening. In a word, present studies all demonstrated 5% SCPP/D/CPC composites could be a potential candidate material employed in bone regeneration and reconstruction for excellent mechanical property and cytocompatibility.
Article
Bacteriocins, which are antimicrobial peptides, are a potential alternative to current ineffective antimicrobial therapies. They can inhibit the growth of clinically relevant pathogens but their proteinaceous nature renders them susceptible to degradation and deactivation in vivo. We have designed injectable polysaccharide hydrogels for the controlled release of an incorporated bacteriocin, nisin. Nisin was encapsulated into these hydrogels which were composed of varying percentages of oxidised dextran, alginate functionalised with hydrazine groups and glycol chitosan. The nisin gels exhibited antimicrobial activity against Staphylococcus aureus up to 10 days. The incorporation of a deacetylated chitosan and the reduction of alginate-hydrazine could be used to tune the gel’s swelling behaviour, strength and the subsequent release profile of nisin. Glycol chitosan also shows synergistic inhibition of S. aureus with nisin.
Article
Metal stent implantation is usually applied to alleviate non-operative palliative esophageal obstruction for esophageal cancer in the later period. However, in-stent restenosis after stent implantation limits the esophageal stents' performance due to lack of effective suppression of pathological cells from cancer microenvironment. In previous work, we modified the esophageal stent material 317 L stainless steel (317LSS) surface with a poly-dopamine/poly-ethylenimine/5-fluorouracil layer (PDA/PEI/5-Fu), which had strong anti-tumor and anti-restenosis functions. Nevertheless, the mechanism of PDA/PEI/5-Fu layer against tumor and inflammation remains unclear. In this work, we revealed the mechanism of PDA/PEI/5-Fu suppressing the esophageal cancer related pathological cells (esophageal tumor cells, epithelial cells and fibroblast) and inflammatory cells (macrophages) via series of experiments. Our data suggested that the PEI inhibited viability and E-cadherin expression of the pathological cells, and blocked the NF-κB signal pathway (reducing levels of p-NF-κB proteins); The loaded 5-Fu inhibited the inflammatory factors (TNF-α and IL-1β) release and promoted the anti-inflammation/anti-tumor factors (IL-10 and IL-4) release from macrophages, and also suppressed pathological cells migration; Both the PEI and 5-Fu contributed to the upregulation of Bax and Caspase-3 (pro-tumor-apoptosis factor), as well as the downregulation of Bcl-2 (anti-tumor-apoptosis factor) in esophageal tumor cells. All the results showed that PDA/PEI/5-Fu coating had potential multipath anti-cancer and anti-inflammatory effects in the surface modification of esophageal stents. This article is protected by copyright. All rights reserved.
Article
The development of biodegradable scaffolds able to support cell growth has recently become of great importance. Therefore, the main objective of this work was the development of hybrid scaffolds made from the mixture of two biopolymers (collagen and chitosan) and the comparison of the effect of glutaraldehyde as crosslinking agent with three different crosslinking methods (chemical: genipin; physical: temperature and enzymatic: transglutaminase) in order to look for a promising candidate to substitute it. To achieve this purpose, the mechanical properties, structure, porosity, degree of crosslinking and swelling of the different scaffolds were assessed. The best ratio of biopolymers (collagen:chitosan) to form hybrid scaffolds was 1:1, which improve their mechanical and morphological properties compared to unitary scaffolds (only collagen or chitosan). In addition, the incorporation of 10% w/w transglutaminase (crosslinking agent) with respect to the mass of biopolymers made these scaffolds a good structure for the growth and proliferation of cells.
Article
Polyurethane is a good matrix material with wide application prospects in tissue engineering because of its adjustable and mechanical properties. A novel biodegradable crosslinked poly(ester urethane) (CPU) with flexible poly(caprolactone) (PCL) and hydrophilic poly(ethylene glycol) (PEG) components has been synthesized using a ferric iron catalyst in our laboratory. In the present study, to promote the interaction between the CPU material and cells, the material was superficially modified by silk fibroin (SF) grafting using an aminolysis and glutaraldehyde crosslinking method to achieve a biocompatible material, CPU-SF. Considering the esophageal-specific architecture, three types of scaffolds were fabricated. S1 was a CPU-SF channel (200 μm in diameter and 30 μm in depth with 30 μm of wall thickness) to support muscle regeneration; S2 was the decellularized matrix of the esophageal mucosa/submucosa obtained by enzyme treatment; and S3 was a combination of S1 and S2, aiming to promote esophageal regeneration with histological structure and function. The biological properties and functions of the materials and scaffolds were investigated by qualitative and quantitative analyses using scanning electron microscopy, immunofluorescence staining, cell adhesion and proliferation measurements, and western blotting technology. The results showed that esophageal smooth muscle cells (SMCs) and epithelial cells (ECs) were very well supported by the scaffolds. In particular, SMCs exhibited guided directional growth and ECs infiltrated the acellular mucosa with retained biological functions when co-cultured on the composite scaffold S3. These findings suggest that the composite bionic scaffold will be a good alternative for esophageal replacement.
Article
The original intention for building a tissue-engineered heart valve (TEHV) was to simulate a normal heart valve and overcome the insufficiency of the commonly used heart valve replacement in the clinic. The endothelialization of the TEHV is very important as the endothelialized TEHV can decrease platelet adhesion and delay the valvular calcification decline process. In this work, we encapsulated vascular endothelial growth factor (VEGF) into polycaprolactone (PCL) nanoparticles. Then, through the Michael addition reaction, PCL nanoparticles were introduced onto the decellularized aortic valve to prepare a hybrid valve. The encapsulation efficiency of the PCL nanoparticles for VEGF was up to 82%, and the in vitro accumulated release rate was slow without an evident initial burst release. In addition, the hybrid valve had a decreased hemolysis ratio and possessed antiplatelet adhesion capacity, and it was able to promote the adhesion and proliferation of endothelial cells, covering the surface with a dense cell layer to accelerate endothelialization. An experiment involving the subcutaneous implant in SD rats showed that at week 8, lots of blood capillaries were formed in the hybrid valve. Mechanics performance testing indicated that the mechanical property of the hybrid valve was partly improved. Taken together, we applied a nano-drug controlled release system to fabricate TEHV, and provide an approach for the biofunctionalization of the TEHV scaffold for accelerating endothelialization.
Article
As a novel class of noncoding RNAs (ncRNAs), circular RNAs (circRNAs) have been verified to be potential biomarkers and therapeutic targets for human malignant tumors. However, the thorough understanding of circRNAs in the progression of esophageal squamous cell carcinoma (ESCC) still needs to be improved. This study focused on exploring the function and mechanism of circVRK1 in ESCC. At first, we examined the expression level of circVRK1 in ESCC tissues and cell lines with qRT-PCR. We found that circVRK1 was downregulated in ESCC tissues and cell lines. Kaplan-Meier method was used to analyze the correlation between circVRK1 expression and the overall survival of ESCC patients. Functionally, overexpression of circVRK1 suppressed the cell proliferation, migration and epithelial-mesenchymal transition (EMT) and reversed the radioresistance. Therefore, we identified the tumor suppressive role of circVRK1 in ESCC progression. Mechanistically, circVRK1 positively regulated PTEN by acting as a molecular sponge of miR-624-3p. Moreover, circVRK1 decreased the activity of PI3K/AKT signaling pathway by upregulating PTEN. Rescue assays were carried out to confirm the function of circVRK1-miR-624-3p-PTEN axis in ESCC progression. Our findings showed that circVRK1 suppressed ESCC progression by regulating miR-624-3p/PTEN axis and PI3K/AKT signaling pathway, suggesting the potential therapeutic value of circVRK1 for ESCC.
Article
For various esophageal diseases, the search for alternative techniques for tissue repair has led to significant developments in basic and translational research in the field of tissue engineering. Applied to the esophagus, this concept is based on the in vitro combination of elements judged necessary for in vivo implantation to promote esophageal tissue remodeling. Different methods are currently being explored to develop substitutes using cells, scaffolds, or a combination of both, according to the severity of lesions to be treated. In this review, we discuss recent advances in (1) cell sheet technology for preventing stricture after extended esophageal mucosectomy and (2) full‐thickness circumferential esophageal replacement using tissue‐engineered substitutes. Alternative techniques for repair of the esophagus has led to developments in tissue engineering. Different methods are currently being explored to develop esophageal substitutes using cells, scaffolds, or a combination of both. Our review discusses recent advances in (1) cell sheet technology for preventing stricture after extended esophageal mucosectomy and (2) full‐thickness circumferential esophageal replacement using tissue‐engineered substitutes.
Article
Although mussel-inspired surface chemistry is one of the most utilized strategies for surface functionalization, its practical and/or industrial applications are rather limited, because dip coating can only treat small surface areas and is dependent on the coating vessel. Herein a mussel-inspired, polymer-based, multifunctional, and substrate-independent spray coating strategy for surface modification under extremely mild conditions using mussel-inspired polyglycerol is described. The postfunctionalization of the obtained surface via spray coating with silver nanoparticles results in a nanoparticle embedded coating with excellent, long-term antibacterial properties. Furthermore, a simple method for preparing a superhydrophobic, highly water-repellent coating by coformulation of the mussel-inspired spray coating with hydrophobic nanoparticles is presented.
Article
The pleiotropic pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), represents an important link between chronic inflammation and tumorigenesis. Although accumulating evidence demonstrates that MIF overexpression is implicated in the development and progression of multiple cancers, including esophageal squamous cell carcinoma (ESCC), the molecular mechanisms underlying its tumor-promoting roles in ESCC remain unclear. In the present study, we observed that MIF is overexpressed in ESCC and correlated significantly with lymph node metastasis, advanced clinical stage, and poor survival of ESCC. MIF knockdown attenuated the proliferation, migration, and invasion of ESCC cells in vitro and in vivo. Moreover, blockage of MIF expression decreased the activation of the Akt, MEK/ERK, and NF-κB pathways and enhanced sensitivity to apoptosis. Meanwhile, repression of MIF expression resulted in activation of glycogen synthase kinase 3 beta (GSK3β) and subsequent decrease of active β-catenin, as well as its downstream targets including cyclin D1, matrix metalloproteinase (MMP)-7, c-myc, and c-Jun. Collectively, our results provided mechanistic insights into the tumor-promoting role of MIF in ESCC, and suggested that MIF represents a potential therapeutic target for treatment of ESCC.
Article
After more than four billion years of evolution, nature has created a large number of fascinating living organisms, which show numerous peculiar structures and wonderful properties. Nature can provide sources of plentiful inspiration for scientists to create various materials and devices with special functions and uses. Since Messersmith proposed the fabrication of multifunctional coatings through mussel-inspired chemistry, this field has attracted considerable attention for its promising and exiciting applications. Polydopamine (PDA), an emerging soft matter, has been demonstrated to be a crucial component in mussel-inspired chemistry. In this review, the recent developments of PDA for mussel-inspired surface modification are summarized and discussed. The biomedical applications of PDA-based materials are also highlighted. We believe that this review can provide important and timely information regarding mussel-inspired chemistry and will be of great interest for scientists in the chemistry, materials, biology, medicine and interdisciplinary fields.
Article
The purpose of this study is to investigate the crosslinking interaction between a natural derived oxidized chitosan oligosaccharide (OCOS) and porcine acellular dermal matrix (pADM), and further evaluate the variational properties of the pADM after cross-linked. The shrinkage temperature (Ts) and cross-link density study indicate that the amino groups of lysine or hydroxylysine side groups of collagen could predominantly react with the available aldehyde group of OCOS to form more stable Schiff’s base leading to the improved hydrothermal stability of pADM. Fourier transform infrared (FTIR) spectroscopy, scanning electronic microscopy (SEM), atomic force microscopy (AFM) and X-ray diffraction (XRD) analysis indicate that the structural integrity of collagen (i.e. D-periodicity structure and triple helix) is still maintained after the OCOS treatment. Meanwhile, mechanical properties, hydrophilicity, collagenase degradation and cytotoxicity of pADM after cross-linked have been all promoted obviously Above all, the cytocompatibility analysis implies that when the dosage of OCOS is less than 8%, introducing OCOS into pADM might be favorable for the cell’s adhesion, growth and proliferation. Taken as a whole, the present study demonstrates that OCOS could serve as an ideal cross-linker for the chemical fixation of pADM, which are compatible with its potential applications in biomaterials.
Article
For bioceramic scaffolds employed in clinical applications, excellent bioactivity and tenacity were of great importance. Modifying inorganic SCPP scaffolds with biological macromolecules could obviously improve its bioactivity and eliminate its palpable brittleness. However, it was hard to execute directly due to extremely bad interfacial compatibility between them. In this research, dopamine (DOPA) was introduced onto strontium-doped calcium polyphosphate (SCPP) scaffolds, subsequently the preliminary material was successfully further modified by silk fibroin (SF). SCPP/D/SF possessed suitable biomechanical properties, ability to stimulate angiogenic factor secretion and excellent biocompatibility. Biomechanical examination demonstrated that SCPP/D/SF scaffolds yielded better compressive strength because of improved interfacial compatibility. MTT assay and CLSM observation showed that SCPP/D/SF scaffolds had good cytocompatibility and presented better inducing-cell-migration potential than pure SCPP scaffolds. Meanwhile, its ability to stimulate angiogenic factor secretion was measured through the ELISA assay and immunohistological analysis in vitro and in vivo respectively. The results revealed, superior to SCPP, SCPP/D/SF could effectively promote VEGF and bFGF expression, possibly leading to enhancing angiogenesis and osteogenesis. In a word, SCPP/D/SF could serve as a potential bone tissue engineering scaffold for comparable biomechanical properties and excellent bioactivity. It provided a novel idea for modification of inorganic materials to prepare promising bone tissue engineering scaffolds with the ability to accelerate bone regeneration and vascularization.
Article
In order to induce esophageal muscle cells’ orientation, the silicon wafer with prototype 1 and prototype 2 was designed. Prototype 1 has micro-channels of 200 µm width and 30 µm depth with 30 µm wide wall as the interval. Prototype 2 has channels of 100 µm width and 30 µm depth with a discontinuous wall which has 30 µm gap for each 100 µm channel. The poly(ester urethane) scaffolds with pattern prototype 1 and prototype 2 were fabricated using solution casting method and abbreviated as PU1 and PU2, respectively. Silk fibroin was grafted individually on PU1 and PU2 surface (PU1-SF, PU2-SF) using our previous protocol, aiming at improving scaffolds’ biocompatibility. The primary esophageal smooth muscle cell was seeded to evaluate the scaffolds’ cytocompatibility in vitro. Characterizations like MTT assay, immunocytochemistry, scanning electron microscope, and Western blotting were applied. After that, poly(ester urethane) scaffolds with double patterns, prototype 1 on the exterior, and prototype 2 in the lumen were implanted into the rabbit esophagous to test the regeneration of the muscle tissue. Results from these preliminary tests showed that the growth and differentiation of primary smooth muscle cells were promoted, but also the muscle tissue with endocircular and exolongitudinal architecture was in regenerating, against non-constitution in the animals without the patterned scaffold or with poly(ester urethane) plane membrane at the defaulted sites. This micro-channel pattern together with silk fibroin grafting and vascular endothelial growth factor coating greatly promoted the regeneration of esophageal muscle with normal histological structure.
Article
Tissue engineering, which consists of the combination and in vivo implantation of elements required for tissue remodeling toward a specific organ phenotype, could be an alternative for classical techniques of esophageal replacement. The current hybrid approach entails creation of an esophageal substitute composed of an acellular matrix and autologous epithelial and muscle cells provides the most successful results. Current research is based on the use of mesenchymal stem cells, whose potential for differentiation and proangioogenic, immune-modulator and anti-inflammatory properties are important assets. In the near future, esophageal substitutes could be constructed from acellular "intelligent matrices" that contain the molecules necessary for tissue regeneration; this should allow circumvention of the implantation step and still obtain standardized in vivo biological responses. At present, tissue engineering applications to esophageal replacement are limited to enlargement plasties with absorbable, non-cellular matrices. Nevertheless, the application of existing clinical techniques for replacement of other organs by tissue engineering in combination with a multiplication of translational research protocols for esophageal replacement in large animals should soon pave the way for health agencies to authorize clinical trials.