Melt electrowriting-enabled hybrid platforms: Toward functional biomimetic scaffolds for cellular interaction and tissue regeneration.

Abstract

Melt electrowriting (MEW) is a high-resolution additive manufacturing technique that enables the precise deposition of micro- to submicron-scale fibers, allowing the fabrication of highly ordered 3D fibrous scaffolds. Owing to its unique capability to program scaffold architecture and mechanical properties, MEW has attracted increasing attention for engineering personalized, tissue-specific constructs. However, MEW alone remains insufficient to replicate the hierarchical structural organization and multifunctional complexity of native tissues. To overcome these limitations, MEW is increasingly integrated with other fabrication techniques, including hydrogel infusion, electrospinning, 3D (bio)printing, and sacrificial microchannel strategies. Such hybrid platforms synergistically combine the high-resolution fiber placement of MEW with the multiscale design flexibility and biological versatility of other techniques, enabling on-demand fabrication of hierarchical, compartmentalized, and functionally graded tissue constructs. This review provides a comprehensive and up-to-date overview of MEW-enabled hybrid platforms. We first highlight the core advantages of MEW in biomimetic scaffold design and summarize biopolymers compatible with MEW processing. We then systematically discuss recent advances in integrating MEW with hydrogel infusion, electrospinning, 3D (bio)printing, and sacrificial microchannel strategies, and their representative applications in modulating cell-material interactions and promoting tissue regeneration. Finally, we highlight recent progress in preclinical translation of MEW-enabled tissue constructs and identify challenges and perspectives toward clinical translation. STATEMENT OF SIGNIFICANCE: Melt electrowriting (MEW) offers unparalleled precision in fabricating ordered micro- to submicron-scale fibrous scaffolds, yet its inability to fully replicate the hierarchical complexity of native tissues has driven the emergence of hybrid biofabrication strategies. This review provides a focused and up-to-date overview of MEW-enabled hybrid platforms integrating MEW with hydrogels, electrospinning, 3D (bio)printing, and sacrificial microchannel strategies. It critically discusses biopolymers compatible with MEW processing and highlights how hybrid strategies expand the design space of MEW to enable on-demand fabrication of hierarchical, compartmentalized, and functional tissue constructs. Importantly, this review synthesizes representative examples of successful preclinical translation of MEW-enabled tissue constructs and critically analyzes tissue-specific translational potential and remaining challenges. This review provides a framework to guide rational scaffold design and clinical translation of next-generation MEW-enabled tissue constructs.