Supplementation of GelMA with Minimally Processed Tissue Promotes the Formation of Densely Packed Skeletal-Muscle-Like Tissues.

We present a simple and cost-effective strategy for developing gelatin methacryloyl (GelMA) hydrogels supplemented with minimally processed tissue (MPT) to fabricate densely packed skeletal-muscle-like tissues. MPT powder was prepared from skeletal muscle by freeze-drying, grinding, and sieving. Cell-culture experiments showed that the incorporation of 0.5-2.0% (w/v) MPT into GelMA hydrogels enhances the proliferation of murine myoblasts (C2C12 cells) compared to proliferation in pristine GelMA hydrogels and GelMA supplemented with decellularized skeletal-muscle tissues (DCTs). MPT-supplemented constructs also preserved their three-dimensional (3D) integrity for 28 days. By contrast, analogous pristine GelMA constructs only maintained their structure for 14 days or less. C2C12 cells embedded in MPT-supplemented constructs exhibited a higher degree of cell alignment and reached a significantly higher density than cells loaded in pristine GelMA constructs. Our results suggest that the addition of MPT incorporates a rich source of biochemical and topological cues, such as growth factors, glycosaminoglycans (GAGs), and structurally preserved proteins (e.g., collagen). In addition, GelMA supplemented with MPT showed suitable rheological properties for use as bioinks for extrusion bioprinting. We envision that this simple and cost-effective strategy of hydrogel supplementation will evolve into an exciting spectrum of applications for tissue engineers, primarily in the biofabrication of relevant microtissues for in vitro models and cultured meat and ultimately for the biofabrication of transplant materials using autologous MPT.

Structural and biological engineering of 3D hydrogels for wound healing.

Chronic wounds have become one of the most important issues for healthcare systems and are a leading cause of death worldwide. Wound dressings are necessary to facilitate wound treatment. Engineering wound dressings may substantially reduce healing time, reduce the risk of recurrent infections, and reduce the disability and costs associated. In the path of engineering of an ideal wound dressing, hydrogels have played a leading role. Hydrogels are 3D hydrophilic polymeric structures that can provide a protective barrier, mimic the native extracellular matrix (ECM), and provide a humid environment. Due to their advantages, hydrogels (with different architectural, physical, mechanical, and biological properties) have been extensively explored as wound dressing platforms. Here we describe recent studies on hydrogels for wound healing applications with a strong focus on the interplay between the fabrication method used and the architectural, mechanical, and biological performance achieved. Moreover, we review different categories of additives which can enhance wound regeneration using 3D hydrogel dressings. Hydrogel engineering for wound healing applications promises the generation of smart solutions to solve this pressing problem, enabling key functionalities such as bacterial growth inhibition, enhanced re-epithelialization, vascularization, improved recovery of the tissue functionality, and overall, accelerated and effective wound healing.

Bioinks for 3D Bioprinting: A Scientometric Analysis of Two Decades of Progress.

This scientometric analysis of 393 original papers published from January 2000 to June 2019 describes the development and use of bioinks for 3D bioprinting. The main trends for bioink applications and the primary considerations guiding the selection and design of current bioink components (i.e., cell types, hydrogels, and additives) were reviewed. The cost, availability, practicality, and basic biological considerations (e.g., cytocompatibility and cell attachment) are the most popular parameters guiding bioink use and development. Today, extrusion bioprinting is the most widely used bioprinting technique. The most reported use of bioinks is the generic characterization of bioink formulations or bioprinting technologies (32%), followed by cartilage bioprinting applications (16%). Similarly, the cell-type choice is mostly generic, as cells are typically used as models to assess bioink formulations or new bioprinting methodologies rather than to fabricate specific tissues. The cell-binding motif arginine-glycine-aspartate is the most common bioink additive. Many articles reported the development of advanced functional bioinks for specific biomedical applications; however, most bioinks remain the basic compositions that meet the simple criteria: Manufacturability and essential biological performance. Alginate and gelatin methacryloyl are the most popular hydrogels that meet these criteria. Our analysis suggests that present-day bioinks still represent a stage of emergence of bioprinting technology.