Biofabrication technologies enabling vascularization of organ- scale engineered tissues for clinical translation

Transplantable engineered organs could one day offer life-saving treatments for patients with end-stage organ failure. However, producing hierarchical vascular networks that sustain the viability and function of cells within human-scale organs after implantation remains a major challenge. Sacrificial templating has emerged as a promising strategy that could overcome this challenge by confining fabrication stressors to a temporary scaffold that is later removed, leaving behind perfusable channels for convective transport of nutrients, gases, and waste. However, current sacrificial approaches remain restricted by tradeoffs between tissue size, channel resolution, architectural complexity, and biocompatibility. In this thesis, we use biomaterial and three-dimensional (3D) printing strategies to begin dismantling these tradeoffs, advancing sacrificial templating towards organ-scale engineered tissue vascularization. First, we address biocompatibility and scalability challenges by embedding microparticles within sacrificial templates to enable controlled, rapid template evacuation while preserving cellular viability in the tissue parenchyma. We next address resolution and architecture limitations by combining patterned and self-assembled vascularization approaches. In this combinatorial strategy, we additionally improved in vivo host integration by patterning collagen and endothelial cell “tracks” within cell-laden biological matrices, achieving vascular assemblies that were seamlessly connected with host circulation and were perfused with host red blood cells (RBCs). Notably, we demonstrate that tuning biomaterial and cellular compositions modulate the vascularization response once implanted, enabling volumetric vascularization of centimeter-scale tissues. Finally, we develop an injection molding technique that combines the advanced 3D architectural capabilities of high-resolution stereolithography with the enhanced biocompatibility of sacrificial templating. We additionally demonstrate pipelines for fluid flow analyses and 3D characterizations of vascular networks, supporting iterative design improvements towards organ-specific optimal tissue architectures. Collectively, these contributions advance the field of tissue engineering and regenerative medicine closer to the realization of clinically viable, organ-scale engineered tissues.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Engineering

Grantor

Rice University

Year dc:date.issued

2025

Author dc:creator

• Malkani, Sherina

Committee members dc:contributor.committeemember

• Veiseh, Omid
• Stevens, Kelly R
• Drezek, Rebekah
• Biswal, Sibani L

• Regenerative medicine
• Tissue engineering
• Biomaterials
• 3D printing
• Microfabrication
• Biofabrication
• 3D bioprinting
• sacrificial templating
• engineered tissues
• vascularization

Statement dc:rights

• Copyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1911/118426

OAI identifier oai:identifier

oai:repository.rice.edu:1911/118426