An official website of the United States government
Hydrogel scaffolds that mimic the native extracellular matrix (ECM) environment play a crucial role in tissue engineering. It has been demonstrated that cell behaviors can be affected by not only the hydrogel's physical and chemical properties, but also its three dimensional (3D) geometrical structures. In order to study the influence of 3D geometrical cues on cell behaviors as well as the maturation and function of engineered tissues, it is imperative to develop 3D fabrication techniques for creating micro and nanoscale hydrogel constructs. Among existing techniques that can effectively pattern hydrogels, two-photon polymerization (2PP)-based femtosecond laser 3D printing technology allows one to produce hydrogel structures with a resolution of 100 nm. This article reviews the basics of this technique and some of its applications in tissue engineering.
more »
« less
From Simple to Architecturally Complex Hydrogel Scaffolds for Cell and Tissue Engineering Applications: Opportunities Presented by Two‐Photon Polymerization
Abstract Direct laser writing via two‐photon polymerization (2PP) is an emerging micro‐ and nanofabrication technique to prepare predetermined and architecturally precise hydrogel scaffolds with high resolution and spatial complexity. As such, these scaffolds are increasingly being evaluated for cell and tissue engineering applications. This article first discusses the basic principles and photoresists employed in 2PP fabrication of hydrogels, followed by an in‐depth introduction of various mechanical and biological characterization techniques used to assess the fabricated structures. The design requirements for cell and tissue related applications are then described to guide the engineering, physicochemical, and biological efforts. Three case studies in bone, cancer, and cardiac tissues are presented that illustrate the need for structured materials in the next generation of clinical applications. This paper concludes by summarizing the progress to date, identifying additional opportunities for 2PP hydrogel scaffolds, and discussing future directions for 2PP research.
more »
« less
- Award ID(s):
- 1647837
- PAR ID:
- 10458569
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Healthcare Materials
- Volume:
- 9
- Issue:
- 1
- ISSN:
- 2192-2640
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Bioprinting is an additive manufacturing technique that combines living cells, biomaterials, and biological molecules to develop biologically functional constructs. Three-dimensional (3D) bioprinting is commonly used as anin vitromodeling system and is a more accurate representation ofin vivoconditions in comparison to two-dimensional cell culture. Although 3D bioprinting has been utilized in various tissue engineering and clinical applications, it only takes into consideration the initial state of the printed scaffold or object. Four-dimensional (4D) bioprinting has emerged in recent years to incorporate the additional dimension of time within the printed 3D scaffolds. During the 4D bioprinting process, an external stimulus is exposed to the printed construct, which ultimately changes its shape or functionality. By studying how the structures and the embedded cells respond to various stimuli, researchers can gain a deeper understanding of the functionality of native tissues. This review paper will focus on the biomaterial breakthroughs in the newly advancing field of 4D bioprinting and their applications in tissue engineering and regeneration. In addition, the use of smart biomaterials and 4D printing mechanisms for tissue engineering applications is discussed to demonstrate potential insights for novel 4D bioprinting applications. To address the current challenges with this technology, we will conclude with future perspectives involving the incorporation of biological scaffolds and self-assembling nanomaterials in bioprinted tissue constructs.more » « less
-
Polyurethanes (PUs) are a highly adaptable class of biomaterials that are among some of the most researched materials for various biomedical applications. However, engineered tissue scaffolds composed of PU have not found their way into clinical application, mainly due to the difficulty of balancing the control of material properties with the desired cellular response. A simple method for the synthesis of tunable bioactive poly(ethylene glycol) diacrylate (PEGDA) hydrogels containing photocurable PU is described. These hydrogels may be modified with PEGylated peptides or proteins to impart variable biological functions, and the mechanical properties of the hydrogels can be tuned based on the ratios of PU and PEGDA. Studies with human cells revealed that PU–PEG blended hydrogels support cell adhesion and viability when cell adhesion peptides are crosslinked within the hydrogel matrix. These hydrogels represent a unique and highly tailorable system for synthesizing PU-based synthetic extracellular matrices for tissue engineering applications.more » « less
-
Abstract Bioprinting is an emerging approach for fabricating cell‐laden 3D scaffolds via robotic deposition of cells and biomaterials into custom shapes and patterns to replicate complex tissue architectures. Bioprinting uses hydrogel solutions called bioinks as both cell carriers and structural components, requiring bioinks to be highly printable while providing a robust and cell‐friendly microenvironment. Unfortunately, conventional hydrogel bioinks have not been able to meet these requirements and are mechanically weak due to their heterogeneously crosslinked networks and lack of energy dissipation mechanisms. Advanced bioink designs using various methods of dissipating mechanical energy are aimed at developing next‐generation cellularized 3D scaffolds to mimic anatomical size, tissue architecture, and tissue‐specific functions. These next‐generation bioinks need to have high print fidelity and should provide a biocompatible microenvironment along with improved mechanical properties. To design these advanced bioink formulations, it is important to understand the structure–property–function relationships of hydrogel networks. By specifically leveraging biophysical and biochemical characteristics of hydrogel networks, high performance bioinks can be designed to control and direct cell functions. In this review article, current and emerging approaches in hydrogel design and bioink reinforcement techniques are critically evaluated. This bottom‐up perspective provides a materials‐centric approach to bioink design for 3D bioprinting.more » « less
-
Hydrogels have emerged as a crucial class of materials within the field of tissue engineering. There is growing interest in matching the mechanical properties of hydrogel scaffolds to tissues in the human body and optimizing these properties for cell growth and differentiation. Gelatin methacrylate (GelMA) is a well-accepted, biocompatible hydrogel with tunable mechanical properties. However, the effects of various formulation parameters on its mechanical properties are not well understood. In this study, an array of GelMA scaffold fabrication parameters is evaluated by varying GelMA concentration and ultraviolet light exposure time. Our overarching goal is to characterize the mechanical properties through ultrasound and rheological measurements, providing a framework for GelMA scaffold selection. Pulse-echo ultrasound techniques were used to non-invasively determine the sound speed and attenuation of the scaffolds, revealing significant dependence on GelMA concentration. Steady shear rate and strain- and frequency-controlled oscillatory shear tests using a rotational rheometer (Model: DHR-2, TA Instruments) revealed a range in the levels of shear-thinning as well as viscoelasticity and showed moduli-dependence on both GelMA concentration and light exposure time. Together, this acoustic and rheological characterization can be used to inform the selection of GelMA scaffolds in tissue engineering applications.more » « less
