In vivo printing of growth factor-eluting adhesive scaffolds improves wound healing

Acute and chronic wounds affect millions of people around the world, imposing a growing financial burden on patients and hospitals. Despite the application of current wound management strategies, the physiological healing process is disrupted in many cases, resulting in impaired wound healing. Therefore, more efficient and easy-to-use treatment modalities are needed. In this study, we demonstrate the benefit of in vivo printed, growth factor-eluting adhesive scaffolds for the treatment of full-thickness wounds in a porcine model. A custom-made handheld printer is implemented to finely print gelatin-methacryloyl (GelMA) hydrogel containing vascular endothelial growth factor (VEGF) into the wounds. In vitro and in vivo results show that the in situ GelMA crosslinking induces a strong scaffold adhesion and enables printing on curved surfaces of wet tissues, without the need for any sutures. The scaffold is further shown to offer a sustained release of VEGF, enhancing the migration of endothelial cells in vitro. Histological analyses demonstrate that the administration of the VEGF-eluting GelMA scaffolds that remain adherent to the wound bed significantly improves the quality of healing in porcine wounds. The introduced in vivo printing strategy for wound healing applications is translational and convenient to use in any place, such as an operating room, and does not require expensive bioprinters or imaging modalities

Surface acoustic waves induced micropatterning of cells in gelatin methacryloyl (GelMA) hydrogels

Acoustic force patterning is an emerging technology that provides a platform to control the spatial location of cells in a rapid, accurate, yet contactless manner. However, very few studies have been reported on the usage of acoustic force patterning for the rapid arrangement of biological objects, such as cells, in a three-dimensional (3D) environment. In this study, we report on a bio-acoustic force patterning technique, which uses surface acoustic waves (SAWs) for the rapid arrangement of cells within an extracellular matrix-based hydrogel such as gelatin methacryloyl (GelMA). A proof-of-principle was achieved through both simulations and experiments based on the in-house fabricated piezoelectric SAW transducers, which enabled us to explore the effects of various parameters on the performance of the built construct. The SAWs were applied in a fashion that generated standing SAWs (SSAWs) on the substrate, the energy of which subsequently was transferred into the gel, creating a rapid, and contactless alignment of the cells (<10 s, based on the experimental conditions). Following ultraviolet radiation induced photo-crosslinking of the cell encapsulated GelMA pre-polymer solution, the patterned cardiac cells readily spread after alignment in the GelMA hydrogel and demonstrated beating activity in 5–7 days. The described acoustic force assembly method can be utilized not only to control the spatial distribution of the cells inside a 3D construct, but can also preserve the viability and functionality of the patterned cells (e.g. beating rates of cardiac cells). This platform can be potentially employed in a diverse range of applications, whether it is for tissue engineering, in vitro cell studies, or creating 3D biomimetic tissue structures

Aerobic Exercise and Scaffolds with Hierarchical Porosity Synergistically Promote Functional Recovery Post Volumetric Muscle Loss

Volumetric muscle loss (VML) is a composite loss of skeletal muscle tissue (greater than 20%) that heals with minimal muscle regeneration, substantial fibrosis, and subsequent functional deficits. Standard treatment, involving free functional muscle transfer and physical therapy, cannot restore full muscle function following VML. Tissue engineered scaffolds, 3D structural templates that mimic native extracellular matrix, are promising to enhance functional muscle formation and recovery. Bioprinted 3D scaffolds are engineered using bioinks, created from scaffolding material, cells, and growth factors, to replicate skeletal muscle architecture with precise control over their spatial deposition. METHODS: The present study evaluates a 3D-printed foam-like scaffold for the treatment of VML in a murine model. This colloidal foam-like scaffold was developed to have high porosity to improve tissue ingrowth, in contrast to dense polymeric scaffolds that routinely resulted in very poor tissue ingrowth, and sufficient stiffness to maintain its shape

Approximating Scaffold Printability Utilizing Computational Methods

Bioprinting facilitates the generation of complex, three-dimensional (3D), cell-based constructs for various applications. Although multiple bioprinting technologies have been developed, extrusion-based systems have become the dominant technology due to the diversity of materials (bioinks) that can be utilized, either individually or in combination. However, each bioink has unique material properties and extrusion characteristics that affect bioprinting utility, accuracy, and precision. Here, we have extended our previous work to achieve high precision (i.e. repeatability) and printability across samples by optimizing bioink-specific printing parameters. Specifically, we hypothesized that a fuzzy inference system (FIS) could be used as a computational method to address the imprecision in 3D bioprinting test data and uncover the optimal printing parameters for a specific bioink that result in high accuracy and precision. To test this hypothesis, we have implemented a FIS model consisting of four inputs (bioink concentration, printing flow rate, speed, and temperature) and two outputs to quantify the precision (scaffold bioprinted linewidth variance) and printability. We validate our use of the bioprinting precision index with both standard and normalized printability factors. Finally, we utilize optimized printing parameters to bioprint scaffolds containing up to 30 × 1

Colloidal multiscale porous adhesive (bio)inks facilitate scaffold integration.

Poor cellular spreading, proliferation, and infiltration, due to the dense biomaterial networks, have limited the success of most thick hydrogel-based scaffolds for tissue regeneration. Here, inspired by whipped cream production widely used in pastries, hydrogel-based foam bioinks are developed for bioprinting of scaffolds. Upon cross-linking, a multiscale and interconnected porous structure, with pores ranging from few to several hundreds of micrometers, is formed within the printed constructs. The effect of the process parameters on the pore size distribution and mechanical and rheological properties of the bioinks is determined. The developed foam bioinks can be easily printed using both conventional and custom-built handheld bioprinters. In addition, the foam inks are adhesive upon in situ cross-linking and are biocompatible. The subcutaneous implantation of scaffolds formed from the engineered foam bioinks showed their rapid integration and vascularization in comparison with their non-porous hydrogel counterparts. In addition, in vivo application of the foam bioink into the non-healing muscle defect of a murine model of volumetric muscle loss resulted in a significant functional recovery and higher muscle forces at 8 weeks post injury compared with non-treated controls

Nanofibrous Silver-Coated Polymeric Scaffolds with Tunable Electrical Properties.

Electrospun micro- and nanofibrous poly(glycerol sebacate)-poly(ε-caprolactone) (PGS-PCL) substrates have been extensively used as scaffolds for engineered tissues due to their desirable mechanical properties and their tunable degradability. In this study, we fabricated micro/nanofibrous scaffolds from a PGS-PCL composite using a standard electrospinning approach and then coated them with silver (Ag) using a custom radio frequency (RF) sputtering method. The Ag coating formed an electrically conductive layer around the fibers and decreased the pore size. The thickness of the Ag coating could be controlled, thereby tailoring the conductivity of the substrate. The flexible, stretchable patches formed excellent conformal contact with surrounding tissues and possessed excellent pattern-substrate fidelity. In vitro studies confirmed the platform's biocompatibility and biodegradability. Finally, the potential controlled release of the Ag coating from the composite fibrous scaffolds could be beneficial for many clinical applications

Nanofibrous Silver-Coated Polymeric Scaffolds with Tunable Electrical Properties

Electrospun micro- and nanofibrous poly(glycerol sebacate)-poly(ε-caprolactone) (PGS-PCL) substrates have been extensively used as scaffolds for engineered tissues due to their desirable mechanical properties and their tunable degradability. In this study, we fabricated micro/nanofibrous scaffolds from a PGS-PCL composite using a standard electrospinning approach and then coated them with silver (Ag) using a custom radio frequency (RF) sputtering method. The Ag coating formed an electrically conductive layer around the fibers and decreased the pore size. The thickness of the Ag coating could be controlled, thereby tailoring the conductivity of the substrate. The flexible, stretchable patches formed excellent conformal contact with surrounding tissues and possessed excellent pattern-substrate fidelity. In vitro studies confirmed the platform’s biocompatibility and biodegradability. Finally, the potential controlled release of the Ag coating from the composite fibrous scaffolds could be beneficial for many clinical applications

Nanofibrous Silver-Coated Polymeric Scaffolds with Tunable Electrical Properties

Electrospun micro- and nanofibrous poly(glycerol sebacate)-poly(ε-caprolactone) (PGS-PCL) substrates have been extensively used as scaffolds for engineered tissues due to their desirable mechanical properties and their tunable degradability. In this study, we fabricated micro/nanofibrous scaffolds from a PGS-PCL composite using a standard electrospinning approach and then coated them with silver (Ag) using a custom radio frequency (RF) sputtering method. The Ag coating formed an electrically conductive layer around the fibers and decreased the pore size. The thickness of the Ag coating could be controlled, thereby tailoring the conductivity of the substrate. The flexible, stretchable patches formed excellent conformal contact with surrounding tissues and possessed excellent pattern-substrate fidelity. In vitro studies confirmed the platform’s biocompatibility and biodegradability. Finally, the potential controlled release of the Ag coating from the composite fibrous scaffolds could be beneficial for many clinical applications. Keywords: electrospinning; electrical properties; nanocoatings; flexible electronic

miRNA‐encapsulated abiotic materials and biovectors for cutaneous and oral wound healing: Biogenesis, mechanisms, and delivery nanocarriers

Abstract MicroRNAs (miRNAs) as therapeutic agents have attracted increasing interest in the past decade owing to their significant effectiveness in treating a wide array of ailments. These polymerases II‐derived noncoding RNAs act through post‐transcriptional controlling of different proteins and their allied pathways. Like other areas of medicine, researchers have utilized miRNAs for managing acute and chronic wounds. The increase in the number of patients suffering from either under‐healing or over‐healing wound demonstrates the limited efficacy of the current wound healing strategies and dictates the demands for simpler approaches with greater efficacy. Various miRNA can be designed to induce pathway beneficial for wound healing. However, the proper design of miRNA and its delivery system for wound healing applications are still challenging due to their limited stability and intracellular delivery. Therefore, new miRNAs are required to be identified and their delivery strategy needs to be optimized. In this review, we discuss the diverse roles of miRNAs in various stages of wound healing and provide an insight on the most recent findings in the nanotechnology and biomaterials field, which might offer opportunities for the development of new strategies for this chronic condition. We also highlight the advances in biomaterials and delivery systems, emphasizing their challenges and resolutions for miRNA‐based wound healing. We further review various biovectors (e.g., adenovirus and lentivirus) and abiotic materials such as organic and inorganic nanomaterials, along with dendrimers and scaffolds, as the delivery systems for miRNA‐based wound healing. Finally, challenges and opportunities for translation of miRNA‐based strategies into clinical applications are discussed