Structure Of Natural Extracellular Matrix Research Articles

Development of mADM-collagen wound dressings for mimicking native skin architecture to enhance skin wound healing

Acellular dermal matrix (ADM) is one of the most promising scaffold materials due to its ability to retain natural extracellular matrix structure. Micronized acellular dermal matrix (mADM) was prepared with no intact cell nuclei and preserved growth factors by High Hydrostatic Pressure (HHP) approach. And mADM-collagen wound dressings were developed with different proportion of type I collagen and recombinant humanized type III collagen. The porous structure of the mADM-collagen wound dressings made them a good candidate for preventing excessive fluid accumulation, while the collagens with gel-like texture combined with mADM powder to form pasty texture wound dressing, which preserving the moisture at the wound site. Moreover, the paste texture of the mADM-collagen wound dressing was easy to reshape to conform any wound shapes and body contours. Furthermore, the resulted mADM-collagen wound dressings showed good biocompatibility by supporting fibroblasts adhesion and proliferation in vitro. Subsequently, a murine model of full-thickness skin wounds was employed to assess its effects on wound healing. Notably, mADM-75% Col-I exhibited superior effects throughout the wound healing process, specifically it promoted neovascularization, skin appendage growth and new skin regeneration. This formulation closely mimicked the collagen ratio found in healthy skin, facilitating the favorable wound repair. These results indicated the superior performance of this mADM-collagen wound dressing providing an optimal environment for wound healing.Graphical

Retention of Key Characteristics of Unprocessed Chorion Tissue Resulting in a Robust Scaffold to Support Wound Healing.

Placental membranes have been widely studied and used clinically for wound care applications, but there is limited published information on the benefits of using the chorion membrane. The chorion membrane represents a promising source of placental-derived tissue to support wound healing, with its native composition of extracellular matrix (ECM) proteins and key regulatory proteins. This study examined the impact of hypothermic storage on the structure of chorion membrane, ECM content, and response to degradation in vitro. Hypothermically stored chorion membrane (HSCM) was further characterized for its proteomic content, and for its functionality as a scaffold for cell attachment and proliferation in vitro. HSCM retained the native ECM structure, composition, and integrity of native unprocessed chorion membrane and showed no differences in response to degradation in an in vitro wound model. HSCM retained key regulatory proteins previously shown to be present in placental membranes and promoted the attachment and proliferation of fibroblasts in vitro. These data support the fact that hypothermic storage does not significantly impact the structure and characteristics of the chorion membrane compared to unprocessed tissue or its functionality as a scaffold to support tissue growth.

A native extracellular matrix material for tissue engineering applications: Characterization of pericardial fluid.

Tissue engineering applications are widely used to repair and regenerate damaged tissues and organs. A scaffold, which is an important component in tissue engineering, provides a 3D environment for cells. In this study, the usability of PF components for the production of an ideal scaffold was investigated. For this aim, pericardial fluid (PF) was harvested from the bovine heart, then its structure and components were characterized. The results of Raman spectroscopy analysis, histological staining, and scanning electron microscopy (SEM) shows that the pericardial fluid contains collagen type I and IV, elastin, fibrin, and glycosaminoglycan (GAG), which are native extracellular matrix (ECM) components. The results demonstrated that (i) PF contains native ECM proteins and GAG such as collagen types I, III, and IV, elastin, and fibrin. (ii) The PF is highly similar to the native ECM structure. (iii) PF can significantly contribute to many tissue engineering studies as a native ECM material to increase the biocompatibility of biomaterials and to several in vitro/in vivo cell culture studies. (iv) PF containing multiple ECM molecules, can be used alone or together with hyaluronic acid, poly(ethylene glycol) (PEG), alginate, chitosan, matrigel, and gelatin methacryloyl (GelMA) materials in bioprinting systems for eliminating the disadvantages of these materials.

Promoting bone regeneration via bioactive calcium silicate nanowires reinforced poly (ε-caprolactone) electrospun fibrous membranes

Bone defects arise from tumors, trauma and congenital disease cause permanent damage to patients. Electrospun technique has attracted great attentions since it can produce nano-/micro-fibers continuously, Furthermore, materials prepared by electrospun can mimic the structure of natural extracellular matrix which play a good biomimetic effect and affect cell behaviors. Our study aimed to fabricate bioactive calcium silicate nanowires reinforced poly (ε-caprolactone) (CS-PCL) composite electrospun fibrous membranes (EFMs) to promote bone regeneration. To prepare CS-PCL composite electrospun fibrous membranes, firstly, hydrothermal treatment was applied to prepare CS nanowires. Secondly, CS were added into PCL solution to fabricate CS-PCL EFMs. The results indicated that the addition of CS into PCL can improve the mechanical properties and hydrophilicity of EFMs. In addition, cell adhesion, proliferation, alkaline phosphatase (ALP) activity and the expression of osteogenic genes were also improved via FAK/JNK/p38 signaling pathways. Lastly, according to the bone regeneration results in skull defect areas, the bone healing effect was significantly enhanced after the addition of CS nanowires. In conclusion, the fabricated CS-PCL EFMs can be a great candidate for bone regeneration.

Decellularization of renal fibrosis by cyclic hydrostatic pressure to restore renal function

Natural extracellular matrices (ECM) are currently being studied as an alternative source for organ transplantation or as new solutions to treat end-stage renal disease. As the gap between donors and patients in need of an organ transplant continues to widen, research in regenerative medicine seeks to provide different strategies for treatment Tissue and organ failure is currently one of the biggest health issues our society faces [1]. Arising from disease or trauma, complete treatment typically requires the repair or replace the affected organ However, the unavailability of adequate organs for transplantation to meet the existing demand has resulted in major organ shortage crisis. As a result, there has been a major increase in the number of patients [2]. The stem cell therapy fails because of the toxic environment in the organ, the implanted cells unable to regenerate. Afterwards researchers are trying to prepare the lab made artificial organ in the laboratory with the help of artificial scaffold and the tissue specific stem cells. Then tried for the transplantation of animal organs. To overcome this organ shortage challenge is the use of organ-derived scaffolds obtained via decellularization techniques by removing all viable cells from native tissues and retaining 3D structure of natural extracellular matrix (ECM) and vascular network for regeneration. This is the most adequate method where scaffold thoroughly decellularizes, free of endotoxin or bacterial contamination. An appropriate macro and microstructure to support physiological function, intact vascular tree, specific location cues.

PVA/PEO/PVA-g-APEG nanofiber membranes with cytocompatibility and anti-cell adhesion for biomedical applications

To prepare novel medical dressings with excellent comprehensive properties, this work uses the polyvinyl alcohol-allyl polyethylene glycol graft copolymer (PVA-g-APEG) synthesized in our previous work as a modifier. The polyvinyl alcohol (PVA)/polyethylene oxide (PEO)/PVA-g-APEG nanofiber membranes with different PVA-g-APEG contents are successfully prepared by electrospinning technology. The biomimetic natural extracellular matrix structure of nanofiber membranes is achieved by regulating the PVA-g-APEG contents. As the content of PVA-g-APEG is 4 wt%, the diameter distribution of nanofibers is the narrowest. The average diameter of nanofibers reaches the minimum value of 267.18 nm, and the porosity of nanofiber membranes reaches the maximum value of 77.90%. Meanwhile, nanofiber membranes possess excellent biocompatibility. The absorption capacity of the nanofiber membranes for different liquids is improved with higher PVA-g-APEG content. The nanofiber membranes become soft and slippery after contact with liquid, effectively avoiding adhesion with cells. The cell proliferation rate is higher than 100%, and the cytotoxicity grade is 0. Additionally, the mechanisms of intermolecular interactions, crystallization and mechanical properties change of nanofiber membranes are discussed systematically. It provides a method and idea for preparing high-strength PVA/PEO nanofiber membranes and realizing the practical application of PVA/PEO composite systems in medical dressings.

Recent advances in smart‐responsive hydrogels for tissue repairing

AbstractThe rapid development of biomedical materials and tissue engineering technology has played an increasingly important role in the process of tissue repair in recent years. Smart‐responsive hydrogels are three‐dimensional network structures formed by cross‐linking of hydrophilic polymers. In addition to having conventional hydrogels that approximate the natural extracellular matrix structure and serve as delivery vehicles for functional molecules (drugs and proteins). More importantly, smart‐responsive hydrogels can achieve relevant changes in material morphology or properties under the conditions of changes in physical, chemical, and biological factors, thereby achieving controlled functional molecules release. It is more urgent to design and build smart‐responsive hydrogels to achieve precise tissue repair with the introduction of the concept of precision medicine and drug delivery. In this review, we highlight different types of smart‐responsive hydrogels and their mechanisms of response to different stimuli and discuss their potential for application in different types of tissue repair, such as chronic wound repair, damaged heart tissue repair, brain nerve tissue repair, and other fields. Finally, we present the prospects of smart‐responsive hydrogels in tissue repair. In general, the current progress in the application of smart‐responsive hydrogels in tissue repair lays the foundation for future applications in other diseases.

Bacterial cellulose reinforced chitosan-based hydrogel with highly efficient self-healing and enhanced antibacterial activity for wound healing

Biocompatible hydrogels with versatile functions are highly desired for demanding the complicated tissue issues, including irregular site and motional wound. Herein, a bio-based hydrogel with multifunctional properties is designed based on quaternized chitosan and dialdehyde bacterial cellulose. As a functional wound dressing, the hydrogel shows rapid self-healing performance and injectable behaviors due to dynamic Schiff-base interactions and presents superior antibacterial activity against E. coli (gram-negative) and S. aureus (gram-positive). The constructed 3D hydrogel also exhibits proper compressive property, desired water retention capacity. To be mentioned, the hydrogel could mimic the structure of natural extracellular matrix (ECM) in the presence of bacterial cellulose nanofibers. Thus, the biopolymer-based hydrogel shows good biocompatibility in terms of cell proliferation and cell spreading. The prepared chitosan-based hydrogel with self-healing, antibacterial, and low cost will become a promising biomaterial for wound healing.

Injectable and Self-Healing Probiotics-Loaded Hydrogel for Promoting Superbacteria-Infected Wound Healing.

Superbacteria-induced skin wound infections are huge health challenges, resulting in significant financial and medical costs due to notable morbidity and mortality worldwide. Probiotics are found in the skin and are effective in treating bacterial infection, moderating the microbial dysbiosis and inflammation induced by pathogens, regulating the immune system, as well as even promoting tissue repair. However, improving their colonization efficiency and viability remains a large obstacle for proper applications. Inspired by probiotic therapy and the natural extracellular matrix structure, hyaluronate-adipic dihydrazide/aldehyde-terminated Pluronic F127/fucoidan hydrogels loaded with Lactobacillus rhamnosus (HPF@L.rha) with unique (bio)physicochemical characteristics were developed through the dynamic Schiff-base reaction for superbacteria-infected trauma management. The developed HPF@L.rha exhibit a shortened gelation time, enhanced mechanical strength, and excellent self-healing and liquid-absorption abilities. Importantly, their anti-superbacteria (Pseudomonas aeruginosa) effect was greatly increased in a dose-dependent fashion. Additionally, in vitro evaluation shows that the prepared HPF@L.rha containing appropriate probiotic concentrations (less than 1 × 107 CFU/mL) possess satisfactory cytocompatibility and blood compatibility. Further, compared to the HPF hydrogel, in vivo the hydrogel combined with probiotics significantly inhibits P. aeruginosa infection and inflammation, promotes the formation of re-epithelialization and collagen, and thus accelerates full-thickness superbacteria-infected wound repair, which is comparable to commercial Prontosan gel formulation. This work suggests that the combination of biomimicking hydrogels and probiotic therapy displays the great potential to manage superbug-infected trauma.

Amorphous silica fiber matrix biomaterials: An analysis of material synthesis and characterization for tissue engineering.

Silica biomaterials including Bioglass offer great biocompatibility and bioactivity but fail to provide pore and degradation features needed for tissue engineering. Herein we report on the synthesis and characterization of novel amorphous silica fiber matrices to overcome these limitations. Amorphous silica fibers were fused by sintering to produce porous matrices. The effects of sacrificial polymer additives such as polyvinyl alcohol (PVA) and cellulose fibers (CF) on the sintering process were also studied. The resulting matrices formed between sintering temperatures of 1,350–1,550 °C retained their fiber structures. The matrices presented pores in the range of 50–200 μm while higher sintering temperatures resulted in increased pore diameter. PVA addition to silica significantly reduced the pore diameter and porosity compared with silica matrices with or without the addition of CF. The PVA additive morphologically appeared to fuse the silica fibers to a greater extent and resulted in significantly higher compressive modulus and strength than the rest of the matrices synthesized. These matrices lost roughly 30% of their original mass in an in vitro degradation study over 40 weeks. All matrices absorbed 500 wt% of water and did not change in their overall morphology, size, or shape with hydration. These fiber matrices supported human mesenchymal stem cell adhesion, proliferation, and mineralized matrix production. Amorphous silica fiber biomaterials/matrices reported here are biodegradable and porous and closely resemble the native extracellular matrix structure and water absorption capacity. Extending the methodology reported here to alter matrix properties may lead to a variety of tissue engineering, implant, and drug delivery applications.

3D Imaging of the Liver Extracellular Matrix in a Mouse Model of Non-Alcoholic Steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is the most common chronic liver disease in the United States, affecting more than 70 million Americans. NASH can progress to fibrosis and eventually to cirrhosis, a significant risk factor for hepatocellular carcinoma. The extracellular matrix (ECM) provides structural support and maintains liver homeostasis via matricellular signals. Liver fibrosis results from an imbalance in the dynamic ECM remodeling process and is characterized by excessive accumulation of structural elements and associated changes in glycosaminoglycans. The typical fibrosis pattern of NASH is called "chicken wire," which usually consists of zone 3 perisinusoidal/pericellular fibrosis, based on features observed by Masson's trichrome stain and Picrosirius Red stains. However, these traditional thin two-dimensional (2D) tissue slide-based imaging techniques cannot demonstrate the detailed three-dimensional (3D) ECM structural changes, limiting the understanding of the dynamic ECM remodeling in liver fibrosis. The current work optimized a fast and efficient protocol to image the native ECM structure in the liver via decellularization to address the above challenges. Mice were fed either with chow or fast-food diet for 14 weeks. Decellularization was performed after in situ portal vein perfusion, and the two-photon microscopy techniques were applied to image and analyze changes in the native ECM. The 3D images of the normal and NASH livers were reconstituted and analyzed. Performing in situ perfusion decellularization and analyzing the scaffold by two-photon microscopy provided a practical and reliable platform to visualize the dynamic ECM remodeling in the liver.

3D Imaging of the Liver Extracellular Matrix in a Mouse Model of Non-Alcoholic Steatohepatitis

Non-alcoholic steatohepatitis (NASH) is the most common chronic liver disease in the United States, affecting more than 70 million Americans. NASH can progress to fibrosis and eventually to cirrhosis, a significant risk factor for hepatocellular carcinoma. The extracellular matrix (ECM) provides structural support and maintains liver homeostasis via matricellular signals. Liver fibrosis results from an imbalance in the dynamic ECM remodeling process and is characterized by excessive accumulation of structural elements and associated changes in glycosaminoglycans. The typical fibrosis pattern of NASH is called "chicken wire," which usually consists of zone 3 perisinusoidal/pericellular fibrosis, based on features observed by Masson's trichrome stain and Picrosirius Red stains. However, these traditional thin two-dimensional (2D) tissue slide-based imaging techniques cannot demonstrate the detailed three-dimensional (3D) ECM structural changes, limiting the understanding of the dynamic ECM remodeling in liver fibrosis. The current work optimized a fast and efficient protocol to image the native ECM structure in the liver via decellularization to address the above challenges. Mice were fed either with chow or fast-food diet for 14 weeks. Decellularization was performed after in situ portal vein perfusion, and the two-photon microscopy techniques were applied to image and analyze changes in the native ECM. The 3D images of the normal and NASH livers were reconstituted and analyzed. Performing in situ perfusion decellularization and analyzing the scaffold by two-photon microscopy provided a practical and reliable platform to visualize the dynamic ECM remodeling in the liver.

Advances in Electrospun Nerve Guidance Conduits for Engineering Neural Regeneration.

Injuries to the peripheral nervous system result in devastating consequences with loss of motor and sensory function and lifelong impairments. Current treatments have largely relied on surgical procedures, including nerve autografts to repair damaged nerves. Despite improvements to the surgical procedures over the years, the clinical success of nerve autografts is limited by fundamental issues, such as low functionality and mismatching between the damaged and donor nerves. While peripheral nerves can regenerate to some extent, the resultant outcomes are often disappointing, particularly for serious injuries, and the ongoing loss of function due to poor nerve regeneration is a serious public health problem worldwide. Thus, a successful therapeutic modality to bring functional recovery is urgently needed. With advances in three-dimensional cell culturing, nerve guidance conduits (NGCs) have emerged as a promising strategy for improving functional outcomes. Therefore, they offer a potential therapeutic alternative to nerve autografts. NGCs are tubular biostructures to bridge nerve injury sites via orienting axonal growth in an organized fashion as well as supplying a supportively appropriate microenvironment. Comprehensive NGC creation requires fundamental considerations of various aspects, including structure design, extracellular matrix components and cell composition. With these considerations, the production of an NGC that mimics the endogenous extracellular matrix structure can enhance neuron–NGC interactions and thereby promote regeneration and restoration of function in the target area. The use of electrospun fibrous substrates has a high potential to replicate the native extracellular matrix structure. With recent advances in electrospinning, it is now possible to generate numerous different biomimetic features within the NGCs. This review explores the use of electrospinning for the regeneration of the nervous system and discusses the main requirements, challenges and advances in developing and applying the electrospun NGC in the clinical practice of nerve injuries.

Engineering Vascular Grafts with Multiphase Structures.

Blood vessels in the body are multiphasic organs with microenvironmental niches specific to the cells that inhabit each section. Electrospinning is a fabrication technique used to produce nano- to microfibrous architectures capable of mimicking native extracellular matrix structure. Likewise, polycitrate elastomers are favorable luminal materials for vascular applications because of their hemocompatibility and mechanical properties. Here we describe the procedure for fabricating a biphasic polycitrate elastomer, collagen, and elastin electrospun composite to spatially tailor both composition and architecture for recapitulating the intimal and medial layers of the blood vessel in a vascular graft.

Tissue engineered bovine saphenous vein extracellular matrix scaffolds produced via antigen removal achieve high in vivo patency rates

Diseases of small diameter blood vessels encompass the largest portion of cardiovascular diseases, with over 4.2 million people undergoing autologous vascular grafting every year. However, approximately one third of patients are ineligible for autologous vascular grafting due to lack of suitable donor vasculature. Acellular extracellular matrix (ECM) scaffolds derived from xenogeneic vascular tissue have potential to serve as ideal biomaterials for production of off-the-shelf vascular grafts capable of eliminating the need for autologous vessel harvest. A modified antigen removal (AR) tissue process, employing aminosulfabetaine-16 (ASB-16) was used to create off-the-shelf small diameter (< 3 mm) vascular graft from bovine saphenous vein ECM scaffolds with significantly reduced antigenic content, while retaining native vascular ECM protein structure and function. Elimination of native tissue antigen content conferred graft-specific adaptive immune avoidance, while retention of native ECM protein macromolecular structure resulted in pro-regenerative cellular infiltration, ECM turnover and innate immune self-recognition in a rabbit subpannicular model. Finally, retention of the delicate vascular basement membrane protein integrity conferred endothelial cell repopulation and 100% patency rate in a rabbit jugular interposition model, comparable only to Autograft implants. Alternatively, the lack of these important basement membrane proteins in otherwise identical scaffolds yielded a patency rate of only 20%. We conclude that acellular antigen removed bovine saphenous vein ECM scaffolds have potential to serve as ideal off-the-shelf small diameter vascular scaffolds with high in vivo patency rates due to their low antigen content, retained native tissue basement membrane integrity and preserved native ECM structure, composition and functional properties. Statement of significanceThe use of autologous vessels for the treatment of small diameter vascular diseases is common practice. However, the use of autologous tissue poses significant complications due to tissue harvest and limited availability. Developing an alternative vessel for use for the treatment of small diameter vessel diseases can potentially increase the success rate of autologous vascular grafting by eliminating complications related to the use of autologous vessel and increased availability. This manuscript demonstrates the potential of non-antigenic extracellular matrix (ECM) scaffolds derived from xenogeneic vascular tissue as off-the-shelf vascular grafts for the treatment of small diameter vascular diseases.

Preparation of multilayer electrospun nanofibrous scaffolds containing soluble eggshell membrane as potential dermal substitute.

Electrospinning of natural and synthetic polymers has shown to be a great candidate for the fabrication of tissue engineering scaffolds due to their similarity to the nanofibrous structure of natural extracellular matrix (ECM). Moreover, the addition of ECM-like proteins could enhance the biocompatibility of these scaffolds. In this study, soluble eggshell protein (SEP) was first extracted and synthesized from the raw eggshell membrane. The characteristics and biocompatibility of the extracted SEP were evaluated using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) analysis and 3-(4,5- dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) (MTT) assay. For scaffolds fabrication, a three-layer nanofibrous composite structure was produced using the electrospinning technique. The outer layers composed of polyvinyl alcohol, chitosan, and extracted SEP while the middle layer composed of polyethylene oxide, gelatin, and zinc oxide nanoparticles (ZnO-NPs). For each layer, the electrospinning parameters were adjusted to form bead-free fibers. To improve fibers' stability against body fluids, the produced fibers were crosslinked using glutaraldehyde vapor. Several techniques such as scanning electron microscopy (SEM), energy dispersive X-ray, ATR-FTIR, swelling, tensile test, in vitro biodegradation, and MTT assay were implemented to evaluate the physical, chemical, and biological characterization of the fabricated fibers. The results showed that crosslinked fibers have adequate stability in water, suitable mechanical properties, and promising water uptake capacity. The MTT results also revealed that SEP and ZnO-NPs could increase scaffolds biocompatibility. Moreover, SEM photographs of cultured fibroblasts cells on the scaffolds showed that cells were well attached on the scaffolds and preserve their natural spindle shapes. Altogether, our findings demonstrated that the produced three-layer composite scaffolds are potential candidates for skin tissue engineering.

Tissue Engineered Bovine Saphenous Vein Extracellular Matrix Scaffolds Produced Via Antigen Removal Achieve High &lt;i&gt;In Vivo&lt;/i&gt; Patency Rates

Diseases of small diameter blood vessels encompass the largest portion of cardiovascular diseases, with over 4.2 million people undergoing autologous vascular grafting every year. However, approximately one third of patients are ineligible for autologous vascular grafting due to lack of suitable donor vasculature. Acellular extracellular matrix (ECM) scaffolds derived from xenogeneic vascular tissue have potential to serve as ideal biomaterials for production of an off-the-shelf vascular graft capable of eliminating the need for autologous vessel harvest. Using the antigen removal tissue processing method an off-the-shelf small diameter (< 3 mm) vascular graft from bovine saphenous vein was produced with significantly reduced antigenic content, while retaining the structure and function of its native vascular ECM proteins. Elimination of native tissue antigen content conferred graft-specific adaptive immune avoidance. Retention of native ECM protein macromolecular structure, as assessed by collagen polarization, resulted in pro-regenerative cellular infiltration, ECM turnover and innate immune self-recognition. Finally, retention of the delicate vascular basement membrane protein integrity conferred endothelial cell repopulation and 100% patency rate in a rabbit jugular interposition model, comparable only to Autograft implants. Alternatively, the lack of these important basement membrane proteins in otherwise identical scaffolds yielded a patency rate of only 20%. We conclude that acellular antigen removed bovine saphenous vein ECM scaffolds have potential to serve as ideal off-the-shelf small diameter vascular scaffolds with high in vivo patency rates due to their low antigen content, retained native tissue basement membrane integrity and preserved native ECM structure, composition and functional properties.

Controlled Delivery of Growth Factor by Hierarchical Nanostructured Core-Shell Nanofibers for the Efficient Repair of Critical-Sized Rat Calvarial Defect.

Electrospun nanofibers have received much attention as bone tissue-engineered scaffolds for their capacity to mimic the structure of natural extracellular matrix (ECM). Most studies have reproduced nanofibers with smooth surface for tissue engineering. This is quite different from the triple-helical nanotopography of natural collagen nanofibrils. In this study, hierarchical nanostructures were coated on the surface of drug-loaded core-shell nanofibers to mimic natural collagen nanofibrils. The nanoshish-kebab (SK) structure was decorated regularly on the surface of the nanofibers, and the inner-loaded bone morphogenetic protein 2 (BMP2) exhibited a gentle release pattern, similar to a zero-order release pattern in kinetics. The in vitro study also showed that the SK structure could accelerate cell proliferation, attachment, and osteogenic differentiation. Four groups of scaffolds were implanted in vivo to repair critical-sized rat calvarial defects: (1) PCL/PVA (control); (2) SK-PCL/PVA; (3) PCL/PVA-BMP2; and (4) SK-PCL/PVA-BMP2. Much more bone was formed in the SK-PCL/PVA group (24.57 ± 3.81%) than in the control group (1.21 ± 0.23%). The BMP2-loaded core-shell nanofibers with nanopatterned structure (SK-PCL/PVA-BMP2) displayed the best repair efficacy (76.38 ± 4.13%), followed by the PCL/PVA-BMP2 group (39.86 ± 5.74%). It was believed that the hierarchical nanostructured core-shell nanofibers could promote osteogeneration and that the SK structure showed synergistic ability with nanofiber-loaded BMP2 in vivo for bone regeneration. Thus, this BMP2-loaded core-shell nanofiber scaffold with hierarchical nanostructure holds great potential for bone tissue engineering applications.

Manufacture of PCL scaffolds through electrospinning technology to accommodate Triple Negative Breast Cancer cells culture

Abstract Two-dimensional (2D) cell culture structures are demonstrated to differ from the in vivo environment. Therefore, cells adopt a flattened morphology that may lead to a non-physiological behaviour. For instance, 2D culture induces the differentiation of the cancer stem cells (CSCs), a tumorigenic cell niche whose study is crucial in tumors with a high relapse rate such as the triple negative breast cancer (TNBC). As an alternative, electrospun scaffolds which mimic the native extracellular matrix structure have emerged as a three-dimensional culture support. In this work, two different meshes of 7.5 and 15% of poly(e-caprolactone) (PCL) were fabricated, differentiating in their microstructure. Scaffolds exhibited similar DSC and TGA curves compared with raw PCL, indicating their purity. TNBC MDA-MB-468 cells were seeded on scaffolds and adopted a more elongated morphology when cultured on 15% PCL meshes. Hence, electrospinning PCL scaffolds may become a suitable tool to culture TNBC cells in a more physiological manner.

Extracellular matrix and biomimetic engineering microenvironment for neuronal differentiation.

Extracellular matrix (ECM) influences cell differentiation through its structural and biochemical properties. In nervous system, neuronal behavior is influenced by these ECMs structures which are present in a meshwork, fibrous, or tubular forms encompassing specific molecular compositions. In addition to contact guidance, ECM composition and structures also exert its effect on neuronal differentiation. This short report reviewed the native ECM structure and composition in central nervous system and peripheral nervous system, and their impact on neural regeneration and neuronal differentiation. Using topographies, stem cells have been differentiated to neurons. Further, focussing on engineered biomimicking topographies, we highlighted the role of anisotropic topographies in stem cell differentiation to neurons and its recent temporal application for efficient neuronal differentiation.