2025-08-12 リンショーピング大学
<関連情報>
- https://liu.se/en/news-item/skin-in-a-syringe-a-step-towards-a-new-way-to-heal-burns
- https://advanced.onlinelibrary.wiley.com/doi/10.1002/adhm.202501430
- https://advanced.onlinelibrary.wiley.com/doi/10.1002/adhm.202502262
皮膚再生のための高細胞密度構造のバイオ製造用二相性粒状バイオインク Biphasic Granular Bioinks for Biofabrication of High Cell Density Constructs for Dermal Regeneration
Rozalin Shamasha, Sneha Kollenchery Ramanathan, Kristin Oskarsdotter, Fatemeh Rasti Boroojeni, Aleksandra Zielińska, Sajjad Naeimipour, Philip Lifwergren, Nina Reustle …
Advanced Healthcare Materials Published: 12 June 2025
DOI:https://doi.org/10.1002/adhm.202501430
Graphical Abstract
This study introduces a biphasic granular bioink (µInk) that enables 3D bioprinting of high cell density constructs for dermal regeneration. The bioink promotes cell proliferation, ECM deposition, and neovascularization, leading to tissue integration and reduced scar formation in vivo. This novel approach offers a promising strategy for advancing scar-free wound healing and tissue engineering.
Abstract
Chronic wounds and severe skin injuries pose significant clinical challenges, as existing treatments like cultured epidermal autografts and tissue engineering strategies fail to regenerate functional dermal tissue effectively. These methods often result in scarring due to poor tissue integration, low cell density, and limited extracellular matrix (ECM) production. Conventional skin tissue engineering relies on time-intensive cell expansion, producing constructs that lack the complexity of native dermal structures. Here, a bioprintable biphasic granular hydrogel bioink (µInk) based on cell-laden porous gelatin microcarriers (PGMs) is presented, enabling fabrication of ultra-high cell density constructs that promote ECM production for dermal regeneration in vitro and in vivo. Primary human dermal fibroblasts are cultured and expanded on PGMs in a bioreactor prior µInk formulation. The cell-laden PGMs are cross-linked via copper-free click chemistry, creating a shear-thinning granular bioink. The µInk is 3D bioprinted into structurally stable constructs with high cell viability. In vivo, the bioprinted constructs supported neovascularization, hydrogel remodeling, and tissue integration over 28 days. Cells maintained their tissue-specific phenotype, proliferated, and produced dermal ECM post-transplantation. The µInk offers a promising approach to generating high cell-density constructs for scar-free wound healing and for advancing complex tissue reconstruction.
弾性およびプロテアーゼ応答性形状記憶ハイドロゲルフィラメントの印刷と再配線 Printing and Rerouting of Elastic and Protease Responsive Shape Memory Hydrogel Filaments
Philip Lifwergren, Viktoria Schoen, Sajjad Naeimipour, Lalit Khare, Anna Wunder, Hanna Blom, Jose G. Martinez, Pierfrancesco Pagella, Anders Fridberger, Johan Junker, Daniel Aili
Advanced Healthcare Materials Published: 20 June 2025
Graphical Abstract
A biofabrication strategy, Rerouting of Free-Floating Suspended Hydrogel Filaments (REFRESH), is developed enabling the printing of highly elastic, reconfigurable protease-responsive hydrogel filaments with shape memory properties. The filaments can be manually braided, knotted, and rerouted to create intricate cell-laden 3D architectures, expanding the design space for engineered tissues and biomimetic hydrogel systems.
Abstract
The fabrication of mechanically robust and reconfigurable hydrogel filaments remains a major challenge in biofabrication of perfusable architectures, dynamic tissue models, and complex 3D cell-laden constructs. Conventional extrusion-based bioprinting techniques generate filaments that are soft and fragile, limiting post-processing, scalability, and functional adaptability. Rerouting of Free-Floating Suspended Hydrogel Filaments (REFRESH) is introduced as a biofabrication strategy that integrates an aqueous two-phase system (ATPS)-compatible elastic extracellular matrix mimicking bioink material with a flexible printing and post-processing approach to overcome these constraints. This method enables the formation of highly elastic hydrogel filaments cross-linked via strain-promoted azide-alkyne cycloaddition (SPAAC) of bicyclo[6.1.0]non-4-yne-functionalized hyaluronan, exhibiting a strain at break exceeding 100%. The printed filaments maintain mechanical integrity during manual handling and post-processing using textile-inspired techniques, such as knotting and braiding, into reconfigurable 3D architectures. A distinct shape memory function enables programmed mechanical actuation and recovery of deformed structures. The hydrogel system supports high cell viability across multiple cell types and enables the fabrication of multicellular constructs with spatially defined organization. By incorporating protease-degradable cross-linkers, REFRESH-generated filaments function as sacrificial templates for perfusable tubular structures. This approach significantly expands the biofabrication design space, offering new possibilities for engineering vascularized tissues and complex hydrogel-based architectures.
