skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Extrusion‐Based 3D Bioprinting of Adhesive Tissue Engineering Scaffolds Using Hybrid Functionalized Hydrogel Bioinks
Abstract Adhesive tissue engineering scaffolds (ATESs) have emerged as an innovative alternative means, replacing sutures and bioglues, to secure the implants onto target tissues. Relying on their intrinsic tissue adhesion characteristics, ATES systems enable minimally invasive delivery of various scaffolds. This study investigates development of the first class of 3D bioprinted ATES constructs using functionalized hydrogel bioinks. Two ATES delivery strategies, in situ printing onto the adherend versus printing and then transferring to the target surface, are tested using two bioprinting methods, embedded versus air printing. Dopamine‐modified methacrylated hyaluronic acid (HAMA‐Dopa) and gelatin methacrylate (GelMA) are used as the main bioink components, enabling fabrication of scaffolds with enhanced adhesion and crosslinking properties. Results demonstrate that dopamine modification improved adhesive properties of the HAMA‐Dopa/GelMA constructs under various loading conditions, while maintaining their structural fidelity, stability, mechanical properties, and biocompatibility. While directly printing onto the adherend yields superior adhesive strength, embedded printing followed by transfer to the target tissue demonstrates greater potential for translational applications. Together, these results demonstrate the potential of bioprinted ATESs as off‐the‐shelf medical devices for diverse biomedical applications.  more » « less
Award ID(s):
2044657
PAR ID:
10484505
Author(s) / Creator(s):
; ; ; ; ; ; ;
Publisher / Repository:
Wiley
Date Published:
Journal Name:
Advanced Biology
Volume:
7
Issue:
7
ISSN:
2701-0198
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. 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
  2. Tissue failure at suture lines contributes to complications and readmissions following complex surgeries in distensible organs such as those performed in the lower urinary tract. Excess tension at points of tissue approximation can contribute to abnormal wound healing, urine leaks, infections, and fistula development. A flexible biodegradable adhesive patch that adheres to dynamic tissue and prevents non-targeted adhesion to adjacent tissue is needed to provide support at suture sites throughout the wound healing process. Herein, we have developed a ready-to-use bilayer adhesive patch (BLAP) to reinforce suture lines for application to expandable and dynamic fluid-filled tissues such as the bladder. The external non-adhesive layer of BLAP comprises a bioabsorbable poly(glycerol sebacate) (PGS) elastomer, preventing undesired adhesion to the adjunct tissues. The internal tissue binding layer is composed of PGS modified with L-dopamine (L-DOPA) to allow immediate adhesion to the wet surface of the target tissue. Physical and mechanical properties of the patches were tuned by varying glycerol to sebacate ratios, L-DOPA contents, and curing time to achieve compliance that approximates that of bladder tissue. The candidate PG2S and PG2SD0.018 biomaterials of the designed BLAP demonstrated Young's moduli of 49.4 kPa and 61.5 kPa and stretchability between 174.7% and 223.7%, respectively. BLAP adhered tightly to a porcine bladder repaired cystotomy ex vivo, reinforcing the sutured line and increasing bladder burst pressure more than stand-alone surgical sutures or a commercial bioadhesive glue, Tisseel®. These features, combined with >90% cytocompatibility and biodegradability, render BLAP a promising elastic bioadhesive patch to reinforce suture lines in the bladder. Beyond the urinary tract, BLAP has the potential to be mechanically tuned for a variety of other non-planar, dynamic tissues. 
    more » « less
  3. Abstract Granular, microgel‐based materials have garnered interest as promising tissue engineering scaffolds due to their inherent porosity, which can promote cell infiltration. Adapting these materials for 3D bioprinting, while maintaining sufficient void space to enable cell migration, can be challenging, since the rheological properties that determine printability are strongly influenced by microgel packing and void fraction. In this work, a strategy is proposed to decouple printability and void fraction by blending UV‐crosslinkable gelatin methacryloyl (GelMA) microgels with sacrificial gelatin microgels to form composite inks. It is observed that inks with an apparent viscosity greater than ≈100 Pa s (corresponding to microgel concentrations ≥5 wt%) have rheological properties that enable extrusion‐based printing of multilayered structures in air. By altering the ratio of GelMA to sacrificial gelatin microgels, while holding total concentration constant at 6 wt%, a family of GelMA:gelatin microgel inks is created that allows for tuning of void fraction from 0.20 to 0.57. Furthermore, human umbilical vein endothelial cells (HUVEC) seeded onto printed constructs are observed to migrate into granular inks in a void fraction‐dependent manner. Thus, the family of microgel inks holds promise for use in 3D printing and tissue engineering applications that rely upon cell infiltration. 
    more » « less
  4. Abstract The convergence of nanotechnology and bioprinting is redefining the landscape of tissue engineering, with nanocomposite gelatin methacryloyl (GelMA) bioinks emerging as a transformative platform for the biofabrication of multifunctional tissue‐specific constructs. GelMA, a photocrosslinkable hydrogel, has rapidly gained attention due to its intrinsic bioactivity, tunable mechanical properties, and compatibility with living cells. However, despite its wide applicability regenerating muscle, cartilage, bone, vascular, cardiac, and neural tissues, native GelMA suffers from limited mechanical strength and insufficient biofunctionality to recapitulate the complexity of specialized tissues. To overcome these shortcomings, recent strategies have focused on the incorporation of nanomaterials into GelMA matrices, ranging from inorganic and carbon‐based to metallic, polymeric, and lipidic nanomaterials. These nanocomposite bioprinted scaffolds impart critical enhancements, including improved mechanical robustness, electrical conductivity, stimuli‐responsiveness, and bioactivity, while also enabling advanced functionalities such as controlled drug release and real‐time responsiveness to the cellular microenvironment. This review examines the bioprinting parameters, material synergies, and design strategies governing the performance of nanocomposite GelMA bioinks. By integrating the tunability of photocrosslinkable bioinks with the multifunctionality of nanomaterials, nanocomposite GelMA bioinks represent a next‐generation platform capable of addressing the complex demands of tissue repair and regeneration. 
    more » « less
  5. Abstract IntroductionCoaxial 3D bioprinting has advanced the formation of tissue constructs that recapitulate key architectures and biophysical parameters for in-vitro disease modeling and tissue-engineered therapies. Controlling gene expression within these structures is critical for modulating cell signaling and probing cell behavior. However, current transfection strategies are limited in spatiotemporal control because dense 3D scaffolds hinder diffusion of traditional vectors. To address this, we developed a coaxial extrusion 3D bioprinting technique using ultrasound-responsive gene delivery bioinks. These bioink materials incorporate echogenic microbubble gene delivery particles that upon ultrasound exposure can sonoporate cells within the construct, facilitating controllable transfection. MethodsPhospholipid-coated gas-core microbubbles were electrostatically coupled to reporter transgene plasmid payloads and incorporated into cell-laden alginate bioinks at varying particle concentrations. These bioinks were loaded into the coaxial nozzle core for extrusion bioprinting with CaCl2crosslinker in the outer sheath. Resulting bioprints were exposed to 2.25 MHz focused ultrasound and evaluated for microbubble activation and subsequent DNA delivery and transgene expression. ResultsCoaxial printing parameters were established that preserved the stability of ultrasound-responsive gene delivery particles for at least 48 h in bioprinted alginate filaments while maintaining high cell viability. Successful sonoporation of embedded cells resulted in DNA delivery and robust ultrasound-controlled transgene expression. The number of transfected cells was modulated by varying the number of focused ultrasound pulses applied. The size region over which DNA was delivered was modulated by varying the concentration of microbubbles in the printed filaments. ConclusionsOur results present a successful coaxial 3D bioprinting technique designed to facilitate ultrasound-controlled gene delivery. This platform enables remote, spatiotemporally-defined genetic manipulation in coaxially bioprinted tissue constructs with important applications for disease modeling and regenerative medicine. 
    more » « less