Tissue Engineering. Part A

Chondrocytes are typically known for their anaerobic metabolism both in vivo and under culture conditions in vitro. However, chondrocytes have been shown to display greater biosynthetic activity when subjected to conditions that elicit aerobic metabolism. We have previously shown that tissue formation by chondrocytes can be upregulated by controlling nutrient availability and that this response arises from changes in glucose metabolism. The aim of the present study was to further characterize these changes through 13C-metabolic flux analysis (13C-MFA) as well as to determine the most optimal response...

Tissue engineering strategies show great potential for repairing osteochondral defects in osteoarthritic joints; however, these approaches often rely on passaging cells multiple times to obtain enough cells to produce functional tissue. Unfortunately, monolayer expansion culture causes chondrocyte dedifferentiation, which is accompanied by a phenotypical and morphological shift in chondrocyte properties that leads to a reduction in the quality of de novo cartilage produced. Thus, the objective of this study was to evaluate transcriptional variations during in vitro expansion culture and determine how differences in cell phenotype from monolayer expansion alters development of functional engineered cartilage...

Cellular, compositional, and mechanical gradients are found throughout biological tissues, especially in transition zones between tissue types. Yet, strategies to engineer such gradients have proven difficult due to the complex nature of these tissues. Current strategies for tissue engineering complex gradients often utilize stem cells, however these multipotent cells require direction from environmental cues, which can be difficult to control both in vitro and in vivo. Here, we utilize CRISPR-guided gene-modulation to direct the differentiation of multipotent adipose-derived stem cells (ASCs) to demonstrate the effectiveness of CRISPR-engineered cells in tissue engineering applications...

Expansion of chondrocytes presents a major obstacle in the cartilage regeneration procedure matrix-induced autologous chondrocyte implantation (MACI). Dedifferentiation of chondrocytes during the expansion process leads to the emergence of a fibrotic (chondrofibrotic) phenotype that decreases the chondrogenic potential of the implanted cells. We aim to 1) determine the extent that chromatin architecture of H3K27me3 and H3K9me3 remodels during dedifferentiation and persists after the transfer to a 3D culture; and 2) to prevent this persistent remodeling to enhance the chondrogenic potential of expanded bovine chondrocytes, used as a model system...

Subchondral drilling (SD), a bone marrow stimulation technique, is used to repair cartilage lesions that lack regenerative potential. Cartilage repair outcomes upon SD are typically fibrocartilaginous in nature with inferior functionality. The lack of cues to foster the chondrogenic differentiation of egressed mesenchymal stromal cells (MSCs) upon SD, can be attributed for the poor outcomes. Continuous low-intensity ultrasound (cLIUS) at 3.8 MHz is proposed as a treatment modality for improving cartilage repair outcomes upon marrow stimulation...

Immune checkpoint signaling, such as Programmed cell death protein-1 (PD-1), is a key target for immunotherapy due to its role in dampening immune responses. PD-1 signaling in T cells is regulated by complex physicochemical and mechanical cues. However, how these mechanical forces are integrated with biochemical responses remains poorly understood. Our previous work demonstrated that the use of an immobilizing PEG linker on synthetic microgels for the presentation of a chimeric form of PD-L1, SA-PD-L1, lead to local regulatory responses capable of abrogating allograft rejection in a model of cell-based transplantation...

Successful in vitro culture of small-diameter tissue-engineered vascular grafts (TEVG) requires rapid deposition of biomacromolecules secreted by vascular smooth muscle cells (VSMCs) in a polyglycolic acid (PGA) mesh scaffold's three-dimensional (3D) porous environment. However, common media have lower crowding conditions than in vivo tissue fluids. Additionally, during the early stages of construction, most of the biomolecules secreted by the cells into the medium are lost, which negatively affects the TEVG culture process...

The global population is aging rapidly, posing unprecedented challenges to healthcare systems. This study investigates the often-overlooked role of macrophages in microvascular dysfunction associated with aging. We employ a 3D in vitro hydrogel model to assess the effects of both age and metformin, an anti-aging therapeutic, on macrophage interactions with microvasculature. Metformin's broad cellular impact is a subject of significant interest, yet its precise mechanisms remain unclear. Our research reveals that metformin treatment enhances genetic pathways associated with macrophage mediated support of angiogenesis, resulting in increased microvessel density...

No abstract text is available yet for this article.

Millions of people suffer from tracheal defect worldwide each year, while autograft and allograft cannot meet existing treatment needs. Tissue-engineered trachea substitutes represent a promising treatment for tracheal defect, while lack of precisely personalize treatment abilities. Therefore, development of an artificial trachea that can be used for personalized transplantation is highly desired. Here, we reported the design and fabrication of an artificial trachea based on sericin microsphere by microtissue engineering technology and 3D printing for personalized repair of tracheal defect...

Organoids are 3D in vitro tissue models that are derived from stem cells and can closely mimic the structure and function of human organs. The ability to create organoids that recapitulate the complex cellular architecture of organs has emerged as an innovative technique in biomedical research and drug development. However, traditional methods of organoid culture are time-consuming and often yield low quantities of cells, which has led to the development of 3D bioprinting of organoids from bioinks containing suspended cells and desired scaffolds...

Porous precision-templated scaffolds ( PTS ) with uniform, interconnected, 40 µm pores have shown favorable healing outcomes and a reduced foreign body reaction ( FBR ). Macrophage receptor with collagenous structure ( MARCO ) and toll-like receptors ( TLRs ) have been identified as key surface receptors in the initial inflammatory phase of wound healing. However, the role of MARCO and TLRs in modulating monocyte and macrophage phenotypes within PTS remains uncharacterized. Here, we demonstrate a synergetic relationship between MARCO and TLR signaling in cells inhabiting PTS, where induction with TLR3 or TLR4 agonists to 40 µm scaffold-resident cells upregulates the transcription of MARCO...

Bioprinting describes the printing of biomaterials and cell-laden or cell-free hydrogels with various combinations of embedded bioactive molecules. It encompasses the precise patterning of biomaterials and cells to create scaffolds for different biomedical needs. There are many requirements that bioprinting scaffolds face, and it is ultimately the interplay between the scaffold's structure, properties, processing, and performance that will lead to its successful translation. Among the essential properties that the scaffolds must possess - adequate and appropriate application-specific chemical, mechanical, and biological performance, the mechanical behavior of hydrogel-based bioprinted scaffolds is the key to their stable performance in vivo at the site of implantation...

Tissue engineering scaffolds are often made from the decellularization of tissues. The decellularization of tissues caused by prolonged contact with aqueous detergents might harm the microstructure and leave cytotoxic residues. In this research, we developed a new technique to use supercritical carbon dioxide (Sc-CO2) based decellularization for porcine nerve tissue. The effect of decellularization was analyzed by histological examination, including Hematoxylin and Eosin (H&E), Masson's trichrome (MT) staining, and 4',6-diamidino-2-phenylindole (DAPI) staining...

Fractures occur commonly with multiple injuries, and their incidence has increased in recent years. Trace amounts of cobalt are necessary for many living organisms as it stimulates hematopoiesis and improves bone health. However, cobalt is also toxic, as it might cause allergic reactions and tissue destruction. These factors limit the application of cobalt in some medical fields. We studied the polysaccharide cobalt complex (TPS-Co) prepared from Qingzhuan Dark Tea polysaccharides. We used six-week-old Sprague-Dawley rats to establish a femoral fracture model and evaluated the effects of CoCl2 and TPS-Co on the healing of femoral fractures...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Tissue engineering and wound-healing interventions are often designed for use in diseased and inflamed environments. In this space, endothelial cells (ECs) are crucial regulators of inflammation and healing, as they are the primary contact for recruitment of immune cells as well as production of pro-inflammatory cytokines, which can stimulate or reduce inflammation. Alternatively, proliferation and spreading of endothelial cells results in the formation of new vascular tissue or repair of damaged tissue, both critical for wound healing...

Many surgical tendon repairs fail despite advances in surgical materials and techniques. Tendon repair failure can be partially attributed to the tendon's poor intrinsic healing capacity and the repurposing of sutures from other clinical applications. Electrospun materials show promise as a biological scaffold to support endogenous tendon repair, but their relatively low tensile strength has limited their clinical translation. It is hypothesized that combining electrospun fibres with a stronger material may improve the suture's mechanical properties while retaining biophysical cues necessary to encourage cell-mediated repair...