Matrix Scaffold Research Articles

Bioscaffolds of graphene based-polymeric hybrid materials for myocardial tissue engineering.

Biomaterials currently utilized for the regeneration of myocardial tissue seem to associate with certain restrictions, including deficiency of electrical conductivity and sufficient mechanical strength. These two factors play an important role in cardiac tissue engineering and regeneration. The contractile property of cardiomyocytes depends on directed signal transmission over the electroconductive systems that happen inside the innate myocardium. Because of their distinctive electrical behavior, electroactive materials such as graphene might be used for the regeneration of cardiac tissue. In this review, we aim to provide deep insight into the applications of graphene and graphene derivative-based hybrid polymeric scaffolds in cardiomyogenic differentiation and cardiac tissue regeneration. Synthetic biodegradable polymers are considered as a platform because their degradation can be controlled over time and easily functionalized. Therefore, graphene-polymeric hybrid scaffolds with anisotropic electrical behavior can be utilized to produce organizational and efficient constructs for macroscopic cardiac tissue engineering. In cardiac tissue regeneration, natural polymer based-scaffolds such as chitosan, gelatin, and cellulose can provide a permissive setting significantly supporting the differentiation and growth of the human induced pluripotent stem cells -derived cardiomyocytes, in large part due to their negligible immunogenicity and suitable biodegradability. Cardiac tissue regeneration characteristically utilizes an extracellular matrix (scaffold), cells, and growth factors that enhance cell adhesion, growth, and cardiogenic differentiation. From the various evaluated electroactive polymeric scaffolds for cardiac tissue regeneration in the past decade, graphene and its derivatives-based materials can be utilized efficiently for cardiac tissue engineering.

Matrix scaffolds for endometrium-derived organoid models.

The uterus-lining endometrium is essential to mammalian reproduction, receiving and accommodating the embryo for proper development. Despite its key role, mechanisms underlying endometrial biology (menstrual cycling, embryo interaction) and disease are not well understood. Its hidden location in the womb, and thereby-associated lack of suitable research models, contribute to this knowledge gap. Recently, 3D organoid models have been developed from both healthy and diseased endometrium. These organoids closely recapitulate the tissue's epithelium phenotype and (patho)biology, including in vitro reproduction of the menstrual cycle. Typically, organoids are grown in a scaffold made of surrogate tissue extracellular matrix (ECM), with mouse tumor basement membrane extracts being the most commonly used. However, important limitations apply including their lack of standardization and xeno-derivation which strongly hinder clinical translation. Therefore, researchers are actively seeking better alternatives including fully defined matrices for faithful and efficient growth of organoids. Here, we summarize the state-of-the-art regarding matrix scaffolds to grow endometrium-derived organoids as well as more advanced organoid-based 3D models. We discuss remaining shortcomings and challenges to advance endometrial organoids toward defined and standardized tools for applications in basic research and translational/clinical fields.

Efficacy of a novel self-assembling peptide gel for hemostasis in refractory neoplastic bleeding.

Video 1Outline of how self-assembling peptide gel can be used exvivo.

A Bioglass-Poly(lactic-co-glycolic Acid) Scaffold@Fibrin Hydrogel Construct to Support Endochondral Bone Formation.

Bone tissue engineering using stem cells to build bone directly on a scaffold matrix often fails due to lack of oxygen at the injury site. This may be avoided by following the endochondral ossification route; herein, a cartilage template is promoted first, which can survive hypoxic environments, followed by its hypertrophy and ossification. However, hypertrophy is so far only achieved using biological factors. This work introduces a Bioglass-Poly(lactic-co-glycolic acid@fibrin (Bg-PLGA@fibrin) construct where a fibrin hydrogel infiltrates and encapsulates a porous Bg-PLGA. The hypothesis is that mesenchymal stem cells (MSCs) loaded in the fibrin gel and induced into chondrogenesis degrade the gel and become hypertrophic upon reaching the stiffer, bioactive Bg-PLGA core, without external induction factors. Results show that Bg-PLGA@fibrin induces hypertrophy, as well as matrix mineralization and osteogenesis; it also promotes a change in morphology of the MSCs at the gel/scaffold interface, possibly a sign of osteoblast-like differentiation of hypertrophic chondrocytes. Thus, the Bg-PLGA@fibrin construct can sequentially support the different phases of endochondral ossification purely based on material cues. This may facilitate clinical translation by decreasing in-vitro cell culture time pre-implantation and the complexity associated with the use of external induction factors.

Bioactive Phenylboronic Acid-Functionalized Hyaluronic Acid Hydrogels Induce Chondro-Aggregates and Promote Chondrocyte Phenotype.

Hydrogels have been extensively investigated as biomimetic extracellular matrix (ECM) scaffolds in tissue engineering. The physiological properties of ECM affect cellular behaviors, which is an inspiration for cell-based therapies. Photocurable hyaluronic acid (HA) hydrogel (AHAMA-PBA) modified with 3-aminophenylboronic acid, sodium periodate and methacrylic anhydride simultaneously is constructed in this study. Chondrocytes are then cultured on the surface of the hydrogels to evaluate the effect of the physicochemical properties of the hydrogels on modulating cellular behaviors. Cell viability assays demonstrate that the hydrogel is non-toxic to chondrocytes. The existence of phenylboronic acid (PBA) moieties enhances the interaction of chondrocytes and hydrogel, promoting cell adhesion and aggregation through filopodia. RT-PCR indicates that the gene expression levels of type II collagen, Aggrecan and Sox9 are significantly up-regulated in chondrocytes cultured on hydrogels. Moreover, the mechanical properties of the hydrogels have a significant effect on the cell phenotype, with soft gels (∼2kPa) promoting chondrocytes to exhibit a hyaline phenotype. Overall, PBA-functionalized HA hydrogel with low stiffness exhibits the best effect on promoting the chondrocyte phenotype, which is a promising biomaterial for cartilage regeneration. This article is protected by copyright. All rights reserved.

An extracellular matrix hydrogel from porcine urinary bladder for tissue engineering: In vitro and in vivo analyses.

The necessity to manufacture scaffolds with superior capabilities of biocompatibility and biodegradability has led to the production of extracellular matrix (ECM) scaffolds. Among their advantages, they allow better cell colonization, which enables its successful integration into the hosted tissue, surrounding the area to be repaired and their formulations facilitate placing it into irregular shapes. The ECM from porcine urinary bladder (pUBM) comprises proteins, proteoglycans and glycosaminoglycans which provide support and enable signals to the cells. These properties make it an excellent option to produce hydrogels that can be used in regenerative medicine. The goal of this study was to assess the biocompatibility of an ECM hydrogel derived from the porcine urinary bladder (pUBMh) in vitro using fibroblasts, macrophages, and adipose-derived mesenchymal stem cells (AD-MCSs), as well as biocompatibility in vivo using Wistar rats. Effects upon cells proliferation/viability was measured using MTT assay, cytotoxic effects were analyzed by quantifying lactate dehydrogenase release and the Live/Dead Cell Imaging assay. Macrophage activation was assessed by quantification of IL-6, IL-10, IL-12p70, MCP-1, and TNF-α using a microsphere-based cytometric bead array. For in vivo analysis, Wistar rats were inoculated into the dorsal sub-dermis with pUBMh. The specimens were sacrificed at 24h after inoculation for histological study. The pUBMh obtained showed good consistency and absence of cell debris. The biocompatibility tests in vitro revealed that the pUBMh promoted cell proliferation and it is not cytotoxic on the three tested cell lines and induces the production of pro-inflammatory cytokines on macrophages, mainly TNF-α and MCP-1. In vivo, pUBMh exhibited fibroblast-like cell recruitment, without tissue damage or inflammation. The results show that pUBMh allows cell proliferation without cytotoxic effects and can be considered an excellent biomaterial for tissue engineering.

Decellularized Lung Extracellular Matrix Scaffold Promotes Human Embryonic Stem Cell Differentiation towards Alveolar Progenitors.

Efficient production of functional and mature alveolar epithelial is a major challenge for developing any cell replacement therapy for lung degenerative diseases. The extracellular matrix (ECM) pro-vides a dynamic environment and mediates cellular responses during development and maintenance of tissue functions. The decellularized ECM (dECM) which retains its native-like structure and bio-chemical composition can provide the induction of embryonic stem cell (ESC) differentiation toward the tissue-specific lineages during in vitro culture. Therefore, the aim of this study was to evaluate the effect of sheep lung dECM-derived scaffold on differentiation and further maturation of ESC-derived lung progenitor cells. This study was an experimental study. In the first step, a sheep lung was decellularized to achieve dECM scaffolds and hydrogels. Afterwards, the obtained dECM scaffold was evaluated for collagen and glycosaminoglycan contents, DNA quantification, and its ultrastructure. Next, the three experimental groups: i. Sheep lung dECM-derived scaffold, ii. Sheep lung dECM-derived hydrogel, and iii. Fibronectin-coated plates were compared in their abilities to induce further differentiation of human embryonic stem cells (hESCs)-derived definitive endoderm (DE) into lung progenitor cells. The comparison was evaluated by immuno-staining and real-time polymerase chain reaction (PCR) assessments. We found that the dECM-derived scaffold preserved its composition and native porous structures while lacking nuclei and intact cells. All experimental groups displayed lung progenitor cell differen-tiation as revealed by the RNA and protein expression of NKX2.1, P63 and CK5. DE cells differenti-ated on dECM-derived scaffold and dECMderived hydrogel showed significant upregulation of SOX9 gene expression, a marker of the distal airway epithelium. DE cells differentiated on the dECM-derived scaffold compared to the two other groups, showed enhanced expression of SFTPC (type 2 alveolar epithelial [AT2] cell marker), FOXJ1 (ciliated cell marker), and MUC5A (secretory cell marker) genes. Overall, our results suggest that dECM-derived scaffold improves the differentiation of DE cells towards lung alveolar progenitor cells in comparison with dECM-derived hydrogel and fibronectin-coated plates.

Electrospun decellularized extracellular matrix scaffolds promote the regeneration of injured neurons

Traumatic injury to the spinal cord (SCI) causes the transection of neurons, formation of a lesion cavity, and remodeling of the microenvironment by excessive extracellular matrix (ECM) deposition and scar formation leading to a regeneration-prohibiting environment. Electrospun fiber scaffolds have been shown to simulate the ECM and increase neural alignment and neurite outgrowth contributing to a growth-permissive matrix. In this work, electrospun ECM-like fibers providing biochemical and topological cues are implemented into a scaffold to represent an oriented biomaterial suitable for the alignment and migration of neural cells in order to improve spinal cord regeneration. The successfully decellularized spinal cord ECM (dECM), with no visible cell nuclei and dsDNA content < 50 ng/mg tissue, showed preserved ECM components, such as glycosaminoglycans and collagens. Serving as the biomaterial for 3D printer-assisted electrospinning, highly aligned and randomly distributed dECM fiber scaffolds (< 1 µm fiber diameter) were fabricated. The scaffolds were cytocompatible and supported the viability of a human neural cell line (SH-SY5Y) for 14 days. Cells were selectively differentiated into neurons, as confirmed by immunolabeling of specific cell markers (ChAT, Tubulin ß), and followed the orientation given by the dECM scaffolds. After generating a lesion site on the cell-scaffold model, cell migration was observed and compared to reference poly-ε-caprolactone fiber scaffolds. The aligned dECM fiber scaffold promoted the fastest and most efficient lesion closure, indicating superior cell guiding capabilities of dECM-based scaffolds. The strategy of combining decellularized tissues with controlled deposition of fibers to optimize biochemical and topographical cues opens the way for clinically relevant central nervous system scaffolding solutions.

Assessment of biological properties for decellularized human umbilical cord tissue: Biomaterials in regenerative medicine

Human placental tissues are used as raw materials for applications in regenerative medicine. The extracellular matrix scaffolds which are abundant in collagen, glycosaminoglycans, proteoglycans, growth factors and cytokines are effective in accelerating the healing process. In this study, the processed umbilical cord was assessed for morphological and functional characteristics to assess its competence for regenerative properties in wound healing. The histological analysis of the umbilical cord was assessed with hematoxylin and eosin and immunohistochemistry for type-IV collagen. Physical properties such as ball burst, thickness and moisture were examined. ELISA and multiplex assays were performed to estimate the growth factors and cytokines. Anti-inflammatory properties were assessed using RAW 264.7 cell line. Further, functional aspects were determined through cell proliferation, cell migration and tube formation studies. Histological results revealed the scaffold had retained its structural features like an amnion layer with epithelial cells and sparsely distributed stromal cells in Wharton jelly. Physical properties were consistently maintained across the tissues. Functional analysis showed reduced macrophage proliferation, increased cell proliferation and cell migration validating its efficacy towards wound healing. Altogether data suggest that the umbilical cord is an effective remedial biological cover for wound healing applications with therapeutic potential for tissue repair and regeneration.

Electrospun manuka honey@PVP nanofibers enclosing chitosan-titanate for highly effective wound healing

The major challenge in skin tissue engineering is the creation of physically and functionally suitable extracellular matrix (ECM) scaffolds. A manuka honey-treated polyvinyl pyrrolidine (Mh@PVP) composite was successfully electrospun to produce nanofibrous scaffold that aids in the rapid growth of ECM and serves as a vehicle for drug delivery. Different characterizations namely SEM, XRD, and FTIR were utilized to elucidate the fabricated electrospun nanofibrous scaffolds (ENS). By increasing the concentration of manuka honey (Mh) in the formula, the mechanical, tensile, and conductivity properties of the polyvinyl pyrrolidine (PVP) solutions were significantly improved. As the concentration of honey rose, the width and direction of the ENS produced altered. For wound healing, honey’s ability to heal wounds faster may be boosted by a higher PVP concentration, which makes honey more easily incorporated. Because of its burst-and-continuous methylglyoxal release patterns, which may last for up to seven days, Mh is an excellent choice for helping the body’s healing process. The in vivo assessment of the Mh@PVP nanocomposite nanofiber mat demonstrated a rapid and substantial increase in keratinocyte expression, reflecting great ability for high regenerative wound healing. Most significantly, there is no scarring associated with hair regrowth. This scaffold can mimic skin characteristics and stimulate keratinocyte development.Graphical abstract

Three-dimensional polymer-nanoparticle-liquid ternary composite for ultrahigh augmentation of piezoelectric nanogenerators

The development of flexible nanogenerators that can convert passively generated environmental energy into electricity is crucial for sustainable energy generation. Herein, we rationally designed a polymer-nanoparticle-liquid (PNL) ternary composite, comprising polydopamine-modified barium titanate nanoparticles (PDA-BTO NPs) doped polyvinylidene fluoride (PVDF), and 1H,1H,2H,2H-perfluorodecyltriethoxysilane (PFOES) liquid nanodroplets, for application in piezoelectric nanogenerators (PENGs). The inter-discrete PFOES nanodroplets enabled the formation of a three-dimensional (3D) scaffold matrix in the ternary composite, which is highly beneficial for the stress transfer of PENGs. Finite-element analysis revealed that the ternary composite had a remarkably improved stress transfer ability due to the incorporation of highly deformable PFOES liquid nanodroplets, which increased the net stress exerted on PDA-BTO NPs and the PVDF matrix. The PNL composite-based PENG (PNL-PENG) device exhibited an enhanced piezoelectric performance, achieving an output voltage, current, and power density of 102 V, 10 µA, and 70 μW/cm2, respectively, which are record-high results compared to those achieved by binary composite-based PENGs. Moreover, the PNL-PENG also demonstrated tremendous potential to function as a highly sensitive tactile perception tool for shape recognition. The concept of PNL-PENG devices represents a milestone in the domain of human-machine interaction, taking a significant step toward the advancement of flexible and wearable electronics.

Incompletely Decellularized Tracheal Matrix Scaffold for Tissue Engineering.

Dense cartilaginous extracellular matrix makes decellularization and repopulation of tracheal cartilage difficult. However, the dense matrix isolates cartilaginous antigens from the recipient's immune system. Therefore, allorejection may be avoided by removing antigens from noncartilaginous tissues. In this study, incompletely decellularized tracheal matrix scaffolds were developed for tracheal tissue engineering. Brown Norway rat tracheae were decellularized with 4% sodium deoxycholate treatment. The cell and antigen removal efficacy, histoarchitecture, surface ultrastructure, glycosaminoglycan, collagen contents, mechanical properties, and chondrocyte viability of the scaffold were evaluated in vitro. Brown Norway rat tracheal matrix scaffolds ( n = 6) were implanted subcutaneously into Lewis rats and observed for 4 weeks. Brown Norway rat tracheae ( n = 6) and Lewis rat scaffolds ( n = 6) were implanted as controls. Histologic analysis of macrophage and lymphocyte infiltration was performed. One decellularization cycle removed all cells and antigens from noncartilaginous tissue. Incomplete decellularization preserved the structural integrity of the tracheal matrix and chondrocyte viability. Except for 31% glycosaminoglycan loss, the scaffold had comparable collagen content and tensile and compressive mechanical properties to those of the native trachea. The allogeneic scaffold showed remarkably reduced CD68 + , CD8 + , and CD4 + cell infiltration compared with the allografts and demonstrated similar cell infiltration to the syngeneic scaffold. It also maintained the three-dimensional tracheal structure and cartilage viability in vivo. Incompletely decellularized trachea did not induce immunorejection and maintained the integrity and viability of cartilage in vivo. Tracheal decellularization and repopulation can be simplified for urgent tracheal replacement. The present study describes the development of an incomplete decellularization protocol that creates a decellularized matrix scaffold for tracheal tissue engineering, aiming to provide preliminary data that this method may generate suitable tracheal scaffolds for use in tracheal replacement.

Suspension-cultured taste bud organoids recapitulate &lt;i&gt;in vivo&lt;/i&gt; taste buds

Background: Taste buds are a complex organ and require a plethora of growth factors for their development, homeostasis, and regeneration. Taste bud organoids provide a platform for understanding their development, disease and regeneration.Methods: In this study, we focused on identifying the localization of receptors involved during taste bud development in taste bud organoids, either in an extracellular matrix scaffold (Matrigel) or in the absence of a scaffold with suspension culture.Results: Compared to Matrigel-cultured organoids, suspension organoids showed stable expression of nerve growth factor receptor (NGFR) cells, which are important for innervation. Transporters for glucose metabolism, such as GLUT1, GLUT2, and the insulin receptor (IGF1R), were observed in suspension-cultured organoids. Furthermore, immunostaining for downstream phosphorylated signaling molecules indicated that the NGFR and IGFR pathways were functional and active in the organoids.Conclusion: Based on these results, suspension-cultured organoids may provide an efficient model for mimicking in vivo taste buds compared to conventional Matrigel organoids.

The role of ADAM8 in the mechanophenotype of MDA-MB-231 breast cancer cells in 3D extracellular matrices.

The majority of investigations of cancer cells have been performed in an oversimplified 2D in vitro environment. In the last decade there is a trend toward more sophisticated 3D in vitro cell culture model systems that can bridge the existing gap between 2D in vitro and in vivo experiments in the field of biophysical and cell biological cancer cell research. Here, we hypothesize that the bidirectional interplay between breast cancer cells and their tumor microenvironment is critical for the outcome of the disease. Thereby, the tissue remodeling processes evoked by cancer cells are important for cancer cell-driven mechanical probing of their matrix environment and on cancer cell adhesion and motility. When remodeling processes have been explored, the emphasis was placed on matrix metalloproteinases and rather not on a disintegrin and metalloproteases (ADAMs). However, the role of ADAM8 in cell mechanics regulating cellular motility in 3D collagen matrices is still unclear. Thus, in this study, we focus on the function of ADAM8 in matrix remodeling and migration of 3D extracellular matrix scaffolds. Therefore, human MDA-MB-231 breast carcinoma cells with ADAM8 knocked down, referred to as ADAM8-KD cells, as well as MDA-MB-231 scrambled control cells, referred to as ADAM8-Ctrl cells, have been used to examine their ability to interact with and migrate in dense extracellular 3D matrices. The fiber displacements, as the capacity of cells to deform the environmental 3D matrix scaffold, has been observed. ADAM8-KD cells displace collagen fibers more strongly than ADAM8-Ctrl cells. Moreover, ADAM8-KD cells migrated more numerous in 3D collagen matrices compared to ADAM8-Ctrl cells. The impairment of ADAM8 using the ADAM8 inhibitor BK-1361 led to significantly increased fiber displacements of ADAM8-Ctrl cells to the levels of ADAM8-KD cells. In contrast, the inhibitor had no effect on ADAM8-KD cells in terms of fiber displacements as well as on the quantitative characteristics of cell invasion of ADAM8-Ctrl cells, albeit the cells that were found in the matrix invaded considerably deeper. When matrix remodeling by cells is impaired through GM6001, a broad-band metalloproteinase inhibitor, the fiber displacements of both cell types increased. In fact, ADAM8 is known to degrade fibronectin in a direct and/or indirect manner. The supplementation of fibronectin before polymerization of the 3D collagen matrices caused an enhancement in fiber displacements as well as in cell invasion into fibronectin-collagen matrices of ADAM8-Ctrl cells, whereas the fiber displacements of ADAM8-KD cells did not change. However, fibrinogen and laminin supplementation induced an increase in fiber displacements of both cell types. Thus, the impact of fibronectin on selective increase in fiber displacement of ADAM8-Ctrl cells appears to be ADAM8-dependent. As a consequence, the presence of ADAM8 may provide an explanation for the longstanding controversial results of fibronectin enrichment on malignant progression of cancers such as breast cancer. Finally, ADAM8 is apparently essential for providing cell-driven fiber displacements of the extracellular matrix microenvironment, which fosters 3D motility in a fibronectin-rich environment. Contribution to the field. Currently, the role of ADAM8 has been explored in 2D or at maximum 2.5D in vitro cell culture motility assays. However, the mechanical characteristics of these two cell types have not been examined. In this study, the function of ADAM8 in breast cancer is refined by providing in vitro cell investigations in 3D collagen fiber matrices of various conditions. ADAM8 has been shown to be involved in the reduced generation of fiber displacements and in influencing breast cancer cell migration. However, especially in the presence of fibronectin in 3Dcollagen fiber matrices, the fiber displacements of ADAM8-Ctrl cells are increased.

67 Development of a Physiologically-Relevant in Vitro Model of the Lung, Incorporating Novel Peptide Hydrogels as Biomimetic Extracellular Matrix Scaffolds

Abstract The vast number of different nanomaterials (NMs) in production and under development precludes the complete hazard assessment of each individual substance according to current regulatory standards which require long term in vivo studies. To reduce the burden of in vivo toxicity testing more physiologically relevant in vitro pulmonary models are required to predict the inhalation hazard posed by aerosolized particles, including NMs. Recently significant progress has been made in the development of multi-cell 3D models which mimic the cellular constituents of tissues and organs, few models under development concomitantly take into account the functional role of the extracellular matrix (ECM) in determining the tissue microenvironment and behaviour of cells. This project specifically aims to develop an in vitro model composed of multiple cells-types grown directly in contact with hydrogel scaffolds which mimic the ECM to better replicate the in vivo microenvironment. We hypothesize the novel addition of an ECM mimetic will influence cell phenotype and activation after exposure to NMs. Preliminary data summarising the process of model building and characterisation including selection of appropriate cell lines and gel formulations, optimisation of culture conditions and evaluation of the integrity of the hydrogel scaffolds is presented. This application of this model will then be evaluated for use in toxicology testing of NMs and predictivity of hazard compared to existing data from both simple 2D in vitro systems and in vivo toxicology studies. In future the potential advantages and limitations of the approach will be evaluated and relevant adaptions to be further explored.

OC-065 THE USE OF CAROLINAS COMFORT SCALE TO COMPARE MESH-RELATED SENSATION BETWEEN BIOSYNTHETIC AND SYNTHETIC MESH: A PILOT STUDY

Abstract Aim Bio-synthetic meshes potentially disappear from the body after certain timeframe leaving behind strengthening scaffold matrix when used for Complex Abdominal Wall Reconstruction (CAWR). We used Carolinas comfort scale (CCS) to assess mesh sensation differences between biosynthetic and synthetic mesh at different time points. Material and Methods This pilot study focusses on patients having undergone CAWR within the unit in the last 3 years. Patients were categorised into four groups of 10 patients each; those repaired with synthetic mesh or biosynthetic mesh within the last 8 months and beyond 18 months. All 40 patients answered all questions of the Carolinas CCS. Decision of mesh type was governed by patient characteristics. Results 10 patients were included in each group (total 40 patients) consecutive retrospective enrolment. We excluded those who had further abdominal surgery or clinical recurrence since. 20 patients repaired with biosynthetic and 20 with synthetic were included. Two-way ANOVA and post HOC Turkey's difference test showed significant difference (p&amp;lt;0.05) in scores in favour of less scores for patients repaired with biosynthetic mesh. This was more pronounced in the beyond 18 month group. Component separation did not make a significant difference in mesh sensation. Logistic Regression analysis revealed patients scored higher on questions related to bending, sitting up and exercise and these were linked. Conclusions This outcome provides a review of current surgical practises and meshes, helping surgeons &amp; patients make better informed decisions. Bio-synthetic meshes have better comfort outcomes for patients with lower CCS scores in the long term.

Production of polylactic acid/chitosan polymer matrix scaffold reinforced with zinc oxide particles by 3D printing additive/welding manufacturing method and investigating their properties

Production of polylactic acid/chitosan polymer matrix scaffold reinforced with zinc oxide particles by 3D printing additive/welding manufacturing method and investigating their properties

Responding to ACL Injury and its Treatments: Comparative Gene Expression between Articular Cartilage and Synovium.

The relationship between cartilage and synovium is a rapidly growing area of osteoarthritis research. However, to the best of our knowledge, the relationships in gene expression between these two tissues have not been explored in mid-stage disease development. The current study compared the transcriptomes of these two tissues in a large animal model one year following posttraumatic osteoarthritis induction and multiple surgical treatment modalities. Thirty-six Yucatan minipigs underwent transection of the anterior cruciate ligament. Subjects were randomized to no further intervention, ligament reconstruction, or ligament repair augmented with an extracellular matrix (ECM) scaffold, followed by RNA sequencing of the articular cartilage and synovium at 52 weeks after harvest. Twelve intact contralateral knees served as controls. Across all treatment modalities, the primary difference in the transcriptomes was that the articular cartilage had greater upregulation of genes related to immune activation compared to the synovium-once baseline differences between cartilage and synovium were adjusted for. Oppositely, synovium featured greater upregulation of genes related to Wnt signaling compared to articular cartilage. After adjusting for expression differences between cartilage and synovium seen following ligament reconstruction, ligament repair with an ECM scaffold upregulated pathways related to ion homeostasis, tissue remodeling, and collagen catabolism in cartilage relative to synovium. These findings implicate inflammatory pathways within cartilage in the mid-stage development of posttraumatic osteoarthritis, independent of surgical treatment. Moreover, use of an ECM scaffold may exert a chondroprotective effect over gold-standard reconstruction through preferentially activating ion homeostatic and tissue remodeling pathways within cartilage.

Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate

Longitudinal bone growth relies on endochondral ossification in the cartilaginous growth plate, where chondrocytes accumulate and synthesize the matrix scaffold that is replaced by bone. The chondroprogenitors in the resting zone maintain the continuous turnover of chondrocytes in the growth plate. Malnutrition is a leading cause of growth retardation in children; however, after recovery from nutrient deprivation, bone growth is accelerated beyond the normal rate, a phenomenon termed catch-up growth. Although nutritional status is a known regulator of long bone growth, it is largely unknown whether and how chondroprogenitor cells respond to deviations in nutrient availability. Here, using fate-mapping analysis in Axin2CreERT2 mice, we showed that dietary restriction increased the number of Axin2+ chondroprogenitors in the resting zone and simultaneously inhibited their differentiation. Once nutrient deficiency was resolved, the accumulated chondroprogenitor cells immediately restarted differentiation and formed chondrocyte columns, contributing to accelerated growth. Furthermore, we showed that nutrient deprivation reduced the level of phosphorylated Akt in the resting zone and that exogenous IGF-1 restored the phosphorylated Akt level and stimulated differentiation of the pooled chondroprogenitors, decreasing their numbers. Our study of Axin2CreERT2 revealed that nutrient availability regulates the balance between accumulation and differentiation of chondroprogenitors in the growth plate and further demonstrated that IGF-1 partially mediates this regulation by promoting the committed differentiation of chondroprogenitor cells.

Decellularized Liver Nanofibers Enhance and Stabilize the Long-Term Functions of Primary Human Hepatocytes In Vitro.

Owing to significant differences across species in liver functions, in vitro human liver models are used for screening the metabolism and toxicity of compounds, modeling diseases, and cell-based therapies. However, the extracellular matrix (ECM) scaffold used for such models often does not mimic either the complex composition or the nanofibrous topography of native liver ECM. Thus, here novel methods are developed to electrospin decellularized porcine liver ECM (PLECM) and collagen I into nano- and microfibers (≈200-1000nm) without synthetic polymer blends. Primary human hepatocytes (PHHs) on nanofibers in monoculture or in coculture with nonparenchymal cells (3T3-J2 embryonic fibroblasts or primary human liver endothelial cells) display higher albumin secretion, urea synthesis, and cytochrome-P450 1A2, 2A6, 2C9, and 3A4 enzyme activities than on conventionally adsorbed ECM controls. PHH functions are highest on the collagen/PLECM blended nanofibers (up to 34-fold higher CYP3A4 activity relative to adsorbed ECM) for nearly 7 weeks in the presence of the fibroblasts. In conclusion, it is shown for the first time that ECM composition and topography synergize to enhance and stabilize PHH functions for several weeks in vitro. The nanofiber platform can prove useful for the above applications and to elucidate cell-ECM interactions in the human liver.