Direct Laser Writing: From Materials Synthesis and Conversion to Electronic Device Processing.

Direct Laser Writing (DLW) has been increasingly selected as a microfabrication route for efficient, cost-effective, high-resolution material synthesis and conversion. Concurrently, lasers participate in the patterning and assembly of functional geometries in several fields of application, of which electronics stand out. In this review, recent advances and strategies based on DLW for electronics microfabrication are surveyed and outlined, based on laser material growth strategies.

Evaluation of a co-culture of rapidly isolated chondrocytes and stem cells seeded on tri-layered collagen-based scaffolds in a caprine osteochondral defect model.

Cartilage has poor regenerative capacity and thus damage to the joint surfaces presents a major clinical challenge. Recent research has focussed on the development of tissue-engineered and cell-based approaches for the treatment of cartilage and osteochondral injuries, with current clinically available cell-based approaches including autologous chondrocyte implantation and matrix-assisted autologous chondrocyte implantation. However, these approaches have significant disadvantages due to the requirement for a two-stage surgical procedure and an in vitro chondrocyte expansion phase which increases logistical challenges, hospital times and costs.

Unveiling Human Proteome Signatures of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent but still poorly understood clinical entity. Its current pathophysiological understanding supports a critical role of comorbidities and their chronic effect on cardiac function and structure. Importantly, despite the replication of some HFpEF phenotypic features, to this day, experimental models have failed to bring new effective therapies to the clinical setting.

Human Extracellular-Matrix Functionalization of 3D hiPSC-Based Cardiac Tissues Improves Cardiomyocyte Maturation.

Human induced pluripotent stem cells (hiPSC) possess significant therapeutic potential due to their high self-renewal capability and potential to differentiate into specialized cells such as cardiomyocytes. However, generated hiPSC-derived cardiomyocytes (hiPSC-CM) are still immature, with phenotypic and functional features resembling the fetal rather than their adult counterparts, which limits their application in cell-based therapies, cardiac disease modeling, and drug cardiotoxicity screening. Recent discoveries have demonstrated the potential of the extracellular matrix (ECM) as a critical regulator in development, homeostasis, and injury of the cardiac microenvironment.

Layer-specific stem cell differentiation in tri-layered tissue engineering biomaterials: Towards development of a single-stage cell-based approach for osteochondral defect repair.

Successful repair of osteochondral defects is challenging, due in part to their complex gradient nature. Tissue engineering approaches have shown promise with the development of layered scaffolds that aim to promote cartilage and bone regeneration within the defect. The clinical potential of implanting these scaffolds cell-free has been demonstrated, whereby cells from the host bone marrow MSCs infiltrate the scaffolds and promote cartilage and bone regeneration within the required regions of the defect.

Interindividual heterogeneity affects the outcome of human cardiac tissue decellularization.

The extracellular matrix (ECM) of engineered human cardiac tissues corresponds to simplistic biomaterials that allow tissue assembly, or animal derived off-the-shelf non-cardiac specific matrices. Decellularized ECM from human cardiac tissue could provide a means to improve the mimicry of engineered human cardiac tissues. Decellularization of cardiac tissue samples using immersion-based methods can produce acceptable cardiac ECM scaffolds; however, these protocols are mostly described for animal tissue preparations.

Toward a Microencapsulated 3D hiPSC-Derived Cardiac Microtissue for Recapitulation of Human Heart Microenvironment Features.

The combination of cardiomyocytes (CM) and non-myocyte cardiac populations, such as endothelial cells (EC), and mesenchymal cells (MC), has been shown to be critical for recapitulation of the human heart tissue for cell-based modeling. However, most of the current engineered cardiac microtissues still rely on either (i) murine/human limited primary cell sources, (ii) animal-derived and undefined hydrogels/matrices with batch-to-batch variability, or (iii) culture systems with low compliance with pharmacological high-throughput screenings. In this work, we explored a culture platform based on alginate microencapsulation and suspension culture systems to develop three-dimensional (3D) human cardiac microtissues, which entails the co-culture of human induced pluripotent stem cell (hiPSC) cardiac derivatives including aggregates of hiPSC-CM and single cells of hiPSC-derived EC and MC (hiPSC-EC+MC).

Tissue-specific extracellular matrix scaffolds for the regeneration of spatially complex musculoskeletal tissues.

Biological scaffolds generated from tissue-derived extracellular matrix (ECM) are commonly used clinically for soft tissue regeneration. Such biomaterials can enhance tissue-specific differentiation of adult stem cells, suggesting that structuring different ECMs into multi-layered scaffolds can form the basis of new strategies for regenerating damaged interfacial tissues such as the osteochondral unit. In this study, mass spectrometry is used to demonstrate that growth plate (GP) and articular cartilage (AC) ECMs contain a unique array of regulatory proteins that may be particularly suited to bone and cartilage repair respectively.

Infrapatellar Fat Pad Stem Cells: From Developmental Biology to Cell Therapy.

The ideal cell type to be used for cartilage therapy should possess a proven chondrogenic capacity, not cause donor-site morbidity, and should be readily expandable in culture without losing their phenotype. There are several cell sources being investigated to promote cartilage regeneration: mature articular chondrocytes, chondrocyte progenitors, and various stem cells. Most recently, stem cells isolated from joint tissue, such as chondrogenic stem/progenitors from cartilage itself, synovial fluid, synovial membrane, and infrapatellar fat pad (IFP) have gained great attention due to their increased chondrogenic capacity over the bone marrow and subcutaneous adipose-derived stem cells.

Scaffolds Derived from ECM Produced by Chondrogenically Induced Human MSC Condensates Support Human MSC Chondrogenesis.

Osteoarthritis is a leading cause of disability affecting an increasing number of individuals. However, cartilage replacement therapies are inadequate, and better cartilage regeneration products must be developed. In this work, we describe a human mesenchymal stem cell (hMSC)-based approach for fabricating extracellular matrix (ECM) scaffolds from tissue-engineered cartilage sheets and then for inducing chondrogenesis of reseeded hMSCs within the ECM scaffolds.

Porous Scaffolds Derived from Devitalized Tissue Engineered Cartilaginous Matrix Support Chondrogenesis of Adult Stem Cells.

ECM-derived scaffolds have previously been developed from devitalized native cartilage and successfully used in tissue engineering. Such ECM-based biomaterials are commonly derived from animal tissue, which may not represent the ideal source for applications in human. Native human ECM can be used as an alternative to xenogeneic tissue; however, its supply may be limited, leading to the need for a more readily available source of such biomaterials.

Anisotropic Shape-Memory Alginate Scaffolds Functionalized with Either Type I or Type II Collagen for Cartilage Tissue Engineering.

Regenerating articular cartilage and fibrocartilaginous tissue such as the meniscus is still a challenge in orthopedic medicine. While a range of different scaffolds have been developed for joint repair, none have facilitated the development of a tissue that mimics the complexity of soft tissues such as articular cartilage. Furthermore, many of these scaffolds are not designed to function in mechanically challenging joint environments.

Stem cells display a donor dependent response to escalating levels of growth factor release from extracellular matrix-derived scaffolds.

Numerous growth factor delivery systems have been developed for tissue engineering. However, little is known about how the dose of a specific protein will influence tissue regeneration, or how different patients will respond to altered levels of growth factor presentation. The objective of the present study was to assess stem cell chondrogenesis within extracellular-matrix (ECM)-derived scaffolds loaded with escalating levels of transforming growth factor (TGF)-β3.

Coupling Freshly Isolated CD44(+) Infrapatellar Fat Pad-Derived Stromal Cells with a TGF-β3 Eluting Cartilage ECM-Derived Scaffold as a Single-Stage Strategy for Promoting Chondrogenesis.

An alternative strategy to the use of in vitro expanded cells in regenerative medicine is the use of freshly isolated stromal cells, where a bioactive scaffold is used to provide an environment conducive to proliferation and tissue-specific differentiation in vivo. The objective of this study is to develop a cartilage extracellular matrix (ECM)-derived scaffold that could facilitate the rapid proliferation and chondrogenic differentiation of freshly isolated stromal cells. By freeze-drying cryomilled cartilage ECM of differing concentrations, it is possible to produce scaffolds with a range of pore sizes.

Controlled release of transforming growth factor-β3 from cartilage-extra-cellular-matrix-derived scaffolds to promote chondrogenesis of human-joint-tissue-derived stem cells.

The objective of this study was to develop a scaffold derived from cartilaginous extracellular matrix (ECM) that could be used as a growth factor delivery system to promote chondrogenesis of stem cells. Dehydrothermal crosslinked scaffolds were fabricated using a slurry of homogenized porcine articular cartilage, which was then seeded with human infrapatellar-fat-pad-derived stem cells (FPSCs). It was found that these ECM-derived scaffolds promoted superior chondrogenesis of FPSCs when the constructs were additionally stimulated with transforming growth factor (TGF)-β3.

Infrapatellar fat pad-derived stem cells maintain their chondrogenic capacity in disease and can be used to engineer cartilaginous grafts of clinically relevant dimensions.

A therapy for regenerating large cartilaginous lesions within the articular surface of osteoarthritic joints remains elusive. While tissue engineering strategies such as matrix-assisted autologous chondrocyte implantation can be used in the repair of focal cartilage defects, extending such approaches to the treatment of osteoarthritis will require a number of scientific and technical challenges to be overcome. These include the identification of an abundant source of chondroprogenitor cells that maintain their chondrogenic capacity in disease, as well as the development of novel approaches to engineer scalable cartilaginous grafts that could be used to resurface large areas of damaged joints.