General Semi-Solid Freeze Casting for Uniform Large-Scale Isotropic Porous Scaffolds: An Application for Extensive Oral Mucosal Reconstruction

被引：1

作者：

Chen, Jinlin ^{[1
]}

Zhang, Tianyu ^{[2
,3
,4
]}

Liu, Dan ^{[2
,3
,4
]}

Yang, Fan ^{[2
,3
,4
]}

Feng, Yuan ^{[1
]}

Wang, Ao ^{[1
]}

Wang, Yanchao ^{[5
]}

He, Xueling ^{[6
]}

Luo, Feng ^{[1
]}

Li, Jiehua ^{[1
]}

Tan, Hong ^{[1
]}

Jiang, Lu ^{[2
,3
,4
]}

机构：

[1] Sichuan Univ, Med X Ctr Mat, State Key Lab Polymer Mat Engn, Coll Polymer Sci & Engn, Chengdu 610065, Sichuan, Peoples R China

[2] Sichuan Univ, State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China

[3] Sichuan Univ, Natl Ctr Stomatol, Chengdu 610041, Sichuan, Peoples R China

[4] Sichuan Univ, Natl Clin Res Ctr Oral Dis, West China Hosp Stomatol, Chengdu, Sichuan, Peoples R China

[5] Sichuan Univ, West China Hosp, Dept Neurosurg, Chengdu 610000, Sichuan, Peoples R China

[6] Sichuan Univ, Chengdu 610000, Sichuan, Peoples R China

来源：

SMALL METHODS | 2024年 / 8卷 / 07期

基金：

中国国家自然科学基金;

关键词：

oral mucosal regeneration; porous scaffolds; scalable manufacturing; scarless healing; semi-solid freeze casting; WOUND CONTRACTION; MACROPHAGE POLARIZATION; DIFFERENTIATION; MECHANISMS; SKIN;

D O I：

10.1002/smtd.202301518

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Ice-templated porous biomaterials possess transformative potential in regenerative medicine; yet, scaling up ice-templating processes for broader applications-owing to inconsistent pore formation-remains challenging. This study reports an innovative semi-solid freeze-casting technique that draws inspiration from semi-solid metal processing (SSMP) combined with ice cream-production routines. This versatile approach allows for the large-scale assembly of various materials, from polymers to inorganic particles, into isotropic 3D scaffolds featuring uniformly equiaxed pores throughout the centimeter scale. Through (cryo-)electron microscopy, X-ray tomography, and finite element modeling, the structural evolution of ice grains/pores is elucidated, demonstrating how the method increases the initial ice nucleus density by pre-fabricating a semi-frozen slurry, which facilitates a transition from columnar to equiaxed grain structures. For a practical demonstration, as-prepared scaffolds are integrated into a bilayer tissue patch using biodegradable waterborne polyurethane (WPU) for large-scale oral mucosal reconstruction in minipigs. Systematic analyses, including histology and RNA sequencing, prove that the patch modulates the healing process toward near-scarless mucosal remodeling via innate and adaptive immunomodulation and activation of pro-healing genes converging on matrix synthesis and epithelialization. This study not only advances the field of ice-templating fabrication but sets a promising precedent for scaffold-based large-scale tissue regeneration. A generic semi-solid freeze-casting technique is established, resulting from an elegant coupling of semi-solid metal processing and ice cream. This novel method enables the scalable fabrication of homogeneous, isotropic porous scaffolds for large-scale oral mucosal defect repair. Biomaterial-mediated scar-free mucosal remodeling arises from early wound contracture blocking, caused by innate and adaptive immunomodulation together with comprehensive activation of pro-healing signaling. image

引用

页数：17