A highly porous type II collagen containing scaffold for the treatment of cartilage defects enhances MSC chondrogenesis and early cartilaginous matrix deposition.

A major challenge in cartilage tissue engineering (TE) is the development of instructive and biomimetic scaffolds capable of driving effective mesenchymal stem cell (MSC) chondrogenic differentiation and robust de novo...

Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Features

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease often associated with severe complications that may result in patient morbidity or death. One T2DM etiological agent is chronic hyperglycemia, a condition that induces damaging biological processes, including impactful extracellular matrix (ECM) modifications, such as matrix components accumulation. The latter alters ECM stiffness, triggering fibrosis, inflammation, and pathological angiogenesis. Hence, studying ECM biochemistry and biomechanics in the context of T2DM, or obesity, is highly relevant. With this in mind, we examined both native and decellularized tissues of obese B6.Cg-Lepob/J (ob/ob) and diabetic BKS.Cg-Dock7m+/+LeprdbJ (db/db) mice models, and extensively investigated their histological and biomechanical properties. The tissues analyzed herein were those strongly affected by diabetes—skin, kidney, adipose tissue, liver, and heart. The referred organs and tissues were collected from 8-week-old animals and submitted to classical histological staining, immunofluorescence, scanning electron microscopy, rheology, and atomic force microscopy. Altogether, this systematic characterization has identified significant differences in the architecture of both ob/ob and db/db tissues, namely db/db skin presents loose epidermis and altered dermis structure, the kidneys have clear glomerulopathy traits, and the liver exhibits severe steatosis. The distribution of ECM proteins also pinpoints important differences, such as laminin accumulation in db/db kidneys and decreased hyaluronic acid in hepatocyte cytoplasm in both obese and diabetic mice. In addition, we gathered a significant set of data showing that ECM features are maintained after decellularization, making these matrices excellent biomimetic scaffolds for 3D in vitro approaches. Importantly, mechanical studies revealed striking differences between tissue ECM stiffness of control (C57BL/6J), obese, and diabetic mice. Notably, we have unveiled that the intraperitoneal adipose tissue of diabetic animals is significantly stiffer (G* ≈ 10,000 Pa) than that of ob/ob or C57BL/6J mice (G* ≈ 3000–5000 Pa). Importantly, this study demonstrates that diabetes and obesity selectively potentiate severe histological and biomechanical alterations in different matrices that may impact vital processes, such as angiogenesis, wound healing, and inflammation.

Microfluidic 3D printing polyhydroxyalkanoates-based bionic skin for wound healing

Biomimetic scaffolds with extracellular matrix (ECM)-mimicking structure have been widely investigated in wound healing applications, while insufficient mechanical strength and limited biological activity remain major challenges. Here, we present a microfluidic 3D printing biomimetic polyhydroxyalkanoates-based scaffold with excellent mechanical properties and hierarchical porous structures for enhanced wound healing. This scaffold is composed of poly(3-hydroxybutyrate-4-hydroxybutyrate) (P34HB) and polycaprolactone (PCL), endowing it with excellent tensile strength (2.99 MPa) and degradability (80% of weight loss within 7 days). The ECM-mimicking hierarchical porous structure allows bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) to proliferate and adhere on the scaffolds. Besides, anisotropic composite scaffolds loaded with BMSCs and HUVECs can significantly promote re-epithelization, collagen deposition and capillary formation in rat wound defects, indicating their satisfactory in vivo tissue regenerative activity. These results indicate the feasibility of polyhydroxyalkanoates-based biomimetic scaffolds for skin repair and regeneration, which also provide a promising therapeutic strategy in diverse tissue engineering applications.

Additive manufacturing of cartilage-mimetic scaffolds as off-the-shelf implants for joint regeneration

Biomimetic scaffolds that provide a tissue-specific environment to cells are particularly promising for tissue engineering and regenerative medicine applications. The goal of this study was to integrate emerging additive manufacturing and biomaterial design strategies to produce articular cartilage (AC) mimetic scaffolds that could be used as ‘off-the-shelf’ implants for joint regeneration. To this end alginate sulfate, a sulfated glycosaminoglycan (sGAG) mimic, was used to functionalize porous alginate-based scaffolds and to support the sustained release of transforming growth factor-β3 (TGF-β3). Covalent crosslinking dramatically improved the elasticity of the alginate/alginate sulfate scaffolds, while scaffold architecture could be tailored using a directional freezing technique. Introducing such an anisotropic architecture was found to promote mesenchymal stem cell (MSC) infiltration into the scaffold and to direct the orientation of the deposited extracellular matrix, leading to the development of cartilage tissue with a biomimetic zonal architecture. In vitro experiments also demonstrated the capacity of the sulfated scaffolds to both enhance chondrogenesis of MSCs and to control the release of TGF-β3, leading to the development of a tissue rich in sGAG and type II collagen. The scaffolds were further reinforced with a 3D printed PLCL framework, leading to composite implants that were more elastic than those reinforced with PCL, and which better mimicked the bulk mechanical properties of native cartilage tissue. The ability of this composite scaffold to support chondrogenesis was then confirmed within a dynamic culture system. Altogether, these findings demonstrate the potential of such biomimetic scaffolds as putative ‘single-stage’ or ‘off-the-shelf’ strategies for articular cartilage regeneration.

Bioactive molecules for regenerative pulp capping

Since the discovery of bioactive molecules sequestered in dentine, researchers have been exploring ways to harness their activities for dental regeneration. One specific area, discussed in this review, is that of dental-pulp capping. Dental-pulp caps are placed when the dental pulp is exposed due to decay or trauma in an attempt to enhance tertiary dentine deposition. Several materials are used for dental-pulp capping; however, natural biomimetic scaffolds may offer advantages over manufactured materials such as improved aesthetic, biocompatibility and success rate. The present review discusses and appraises the current evidence surrounding biomimetic dental-pulp capping, with a focus on bioactive molecules sequestered in dentine. Molecules covered most extensively in the literature include transforming growth factors (TGF-βs, specifically TGF-β1) and bone morphogenetic proteins (BMPs, specifically BMP-2 and BMP-7). Further studies would need to explore the synergistic use of multiple peptides together with the development of a tailored scaffold carrier. The roles of some of the molecules identified in dentine need to be explored before they can be considered as potential bioactive molecules in a biomimetic scaffold for dental-pulp capping. Future in vivo work needs to consider the inflammatory environment of the dental pulp in pulpal exposures and compare pulp-capping materials.

Biocompatibility Computation of Muscle Cells on Polyhedral Oligomeric Silsesquioxane-Grafted Polyurethane Nanomatrix

This study was performed to appraise the biocompatibility of polyhedral oligomeric silsesquioxane (POSS)-grafted polyurethane (PU) nanocomposites as potential materials for muscle tissue renewal. POSS nanoparticles demonstrate effectual nucleation and cause noteworthy enhancement in mechanical and thermal steadiness as well as biocompatibility of resultant composites. Electrospun, well-aligned, POSS-grafted PU nanofibers were prepared. Physicochemical investigation was conducted using several experimental techniques, including scanning electron microscopy, energy dispersive X-ray spectroscopy, electron probe microanalysis, Fourier transform infrared spectroscopy, and X-ray diffraction pattern. Adding POSS molecules to PU did not influence the processability and morphology of the nanocomposite; however, we observed an obvious mean reduction in fiber diameter, which amplified specific areas of the POSS-grafted PU. Prospective biomedical uses of nanocomposite were also appraised for myoblast cell differentiation in vitro. Little is known about C2C12 cellular responses to PU, and there is no information regarding their interaction with POSS-grafted PU. The antimicrobial potential, anchorage, proliferation, communication, and differentiation of C2C12 on PU and POSS-grafted PU were investigated in this study. In conclusion, preliminary nanocomposites depicted superior cell adhesion due to the elevated free energy of POSS molecules and anti-inflammatory potential. These nanofibers were non-hazardous, and, as such, biomimetic scaffolds show high potential for cellular studies and muscle regeneration.