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Sacrificial nanofibrous composites provide instruction without impediment and enable functional tissue formation.

ABSTRACT: The fibrous tissues prevalent throughout the body possess an ordered structure that underlies their refined and robust mechanical properties. Engineered replacements will require recapitulation of this exquisite architecture in three dimensions. Aligned nanofibrous scaffolds can dictate cell and matrix organization; however, their widespread application has been hindered by poor cell infiltration due to the tight packing of fibers during fabrication. Here, we develop and validate an enabling technology in which tunable composite nanofibrous scaffolds are produced to provide instruction without impediment. Composites were formed containing two distinct fiber fractions: slow-degrading poly(?-caprolactone) and water-soluble, sacrificial poly(ethylene oxide), which can be selectively removed to increase pore size. Increasing the initial fraction of sacrificial poly(ethylene oxide) fibers enhanced cell infiltration and improved matrix distribution. Despite the removal of >50% of the initial fibers, the remaining scaffold provided sufficient instruction to align cells and direct the formation of a highly organized ECM across multiple length scales, which in turn led to pronounced increases in the tensile properties of the engineered constructs (nearly matching native tissue). This approach transforms what is an interesting surface phenomenon (cells on top of nanofibrous mats) into a method by which functional, 3D tissues (>1 mm thick) can be formed, both in vitro and in vivo. As such, this work represents a marked advance in the engineering of load-bearing fibrous tissues, and will find widespread applications in regenerative medicine.

SUBMITTER: Baker BM

PROVIDER: S-EPMC3435214 | biostudies-other | 2012 Aug

REPOSITORIES: biostudies-other

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Sacrificial nanofibrous composites provide instruction without impediment and enable functional tissue formation.

Baker Brendon M BM Shah Roshan P RP Silverstein Amy M AM Esterhai John L JL Burdick Jason A JA Mauck Robert L RL

Proceedings of the National Academy of Sciences of the United States of America 20120807 35

The fibrous tissues prevalent throughout the body possess an ordered structure that underlies their refined and robust mechanical properties. Engineered replacements will require recapitulation of this exquisite architecture in three dimensions. Aligned nanofibrous scaffolds can dictate cell and matrix organization; however, their widespread application has been hindered by poor cell infiltration due to the tight packing of fibers during fabrication. Here, we develop and validate an enabling tec ...[more]

PMID: 22872864

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Project description:Combating necrosis, by supplying nutrients and removing waste, presents the major challenge for engineering large three-dimensional (3D) tissues. Previous elegant work used 3D printing with carbohydrate glass as a cytocompatible sacrificial template to create complex engineered tissues with vascular networks (Miller et al. 2012, Nature Materials). The fragile nature of this material compounded with the technical complexity needed to create high-resolution structures led us to create a flexible sugar-protein composite, termed Gelatin-sucrose matrix (GSM), to achieve a more robust and applicable material. Here we developed a low-range (25-37˚C) temperature sensitive formulation that can be moulded with micron-resolution features or cast during 3D printing to produce complex flexible filament networks forming sacrificial vessels. Using the temperature-sensitivity, we could control filament degeneration meaning GSM can be used with a variety of matrices and crosslinking strategies. Furthermore by incorporation of biocompatible crosslinkers into GSM directly, we could create thin endothelialized vessel walls and generate patterned tissues containing multiple matrices and cell-types. We also demonstrated that perfused vascular channels sustain metabolic function of a variety of cell-types including primary human cells. Importantly, we were able to construct vascularized human noses which otherwise would have been necrotic. Our material can now be exploited to create human-scale tissues for regenerative medicine applications. STATEMENT OF SIGNIFICANCE: Authentic and engineered tissues have demands for mass transport, exchanging nutrients and oxygen, and therefore require vascularization to retain viability and inhibit necrosis. Basic vascular networks must be included within engineered tissues intrinsically. Yet, this has been unachievable in physiologically-sized constructs with tissue-like cell densities until recently. Sacrificial moulding is an alternative in which networks of rigid lattices of filaments are created to prevent subsequent matrix ingress. Our study describes a biocompatible sacrificial sugar-protein formulation; GSM, made from mixtures of inexpensive and readily available bio-grade materials. GSM can be cast/moulded or bioprinted as sacrificial filaments that can rapidly dissolve in an aqueous environment temperature-sensitively. GSM material can be used to engineer viable and vascularized human-scale tissues for regenerative medicine applications.

Dataset Information

Sacrificial nanofibrous composites provide instruction without impediment and enable functional tissue formation.

Publications

Sacrificial nanofibrous composites provide instruction without impediment and enable functional tissue formation.

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