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Subcutaneously engineered autologous extracellular matrix scaffolds with aligned microchannels for enhanced tendon regeneration: Aligned microchannel scaffolds for tendon repair.

ABSTRACT: Improved strategies for the treatment of tendon defects are required to successfully restore mechanical function and strength to the damaged tissue. This remains a scientific and clinical challenge, given the tendon's limited innate regenerative capacity. Here, we present an engineering solution that stimulates the host cell's remodeling abilities. We combined precision-designed templates with subcutaneous implantation to generate decellularized autologous extracellular matrix (aECM) scaffolds that had highly aligned microchannels after removal of templates and cellular components. The aECM scaffolds promoted rapid cell infiltration, favorable macrophage responses, collagen-rich extracellular matrix (ECM) synthesis, and physiological tissue remodeling in rat Achilles tendon defects. At three months post-surgery, the mechanical strength of tenocyte-populated 'neo-tendons' was comparable to pre-injury state tendons. Overall, we demonstrated an in vivo bioengineering strategy for improved restoration of tendon tissue, which also offers wider implications for the regeneration of other highly organized tissues.

SUBMITTER: Li W

PROVIDER: S-EPMC7376279 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Subcutaneously engineered autologous extracellular matrix scaffolds with aligned microchannels for enhanced tendon regeneration: Aligned microchannel scaffolds for tendon repair.

Li Wen W Midgley Adam C AC Bai Yanli Y Zhu Meifeng M Chang Hong H Zhu Wenying W Wang Lina L Wang Yuhao Y Wang Hongjun H Kong Deling D

Biomaterials 20190912

Improved strategies for the treatment of tendon defects are required to successfully restore mechanical function and strength to the damaged tissue. This remains a scientific and clinical challenge, given the tendon's limited innate regenerative capacity. Here, we present an engineering solution that stimulates the host cell's remodeling abilities. We combined precision-designed templates with subcutaneous implantation to generate decellularized autologous extracellular matrix (aECM) scaffolds t ...[more]

PMID: 31562997

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Project description:UnlabelledNeurotrauma, stroke, and neurodegenerative disease may result in widespread loss of neural cells as well as the complex interconnectivity necessary for proper central nervous system function, generally resulting in permanent functional deficits. Potential regenerative strategies involve the recruitment of endogenous neural stem cells and/or directed axonal regeneration through the use of tissue engineered "living scaffolds" built to mimic features of three-dimensional (3-D) in vivo migratory or guidance pathways. Accordingly, we devised a novel biomaterial encasement scheme using tubular hydrogel-collagen micro-columns that facilitated the self-assembly of seeded astrocytes into 3-D living scaffolds consisting of long, cable-like aligned astrocytic networks. Here, robust astrocyte alignment was achieved within a micro-column inner diameter (ID) of 180μm or 300-350μm but not 1.0mm, suggesting that radius of curvature dictated the extent of alignment. Moreover, within small ID micro-columns, >70% of the astrocytes assumed a bi-polar morphology, versus ∼10% in larger micro-columns or planar surfaces. Cell-cell interactions also influenced the aligned architecture, as extensive astrocyte-collagen contraction was achieved at high (9-12×10(5)cells/mL) but not lower (2-6×10(5)cells/mL) seeding densities. This high density micro-column seeding led to the formation of ultra-dense 3-D "bundles" of aligned bi-polar astrocytes within collagen measuring up to 150μm in diameter yet extending to a remarkable length of over 2.5cm. Importantly, co-seeded neurons extended neurites directly along the aligned astrocytic bundles, demonstrating permissive cues for neurite extension. These transplantable cable-like astrocytic networks structurally mimic the glial tube that guides neuronal progenitor migration in vivo along the rostral migratory stream, and therefore may be useful to guide progenitor cells to repopulate sites of widespread neurodegeneration.Statement of significanceThis manuscript details our development of novel micro-tissue engineering techniques to generate robust networks of longitudinally aligned astrocytes within transplantable micro-column hydrogels. We report a novel biomaterial encasement scheme that facilitated the self-assembly of seeded astrocytes into long, aligned regenerative pathways. These miniature "living scaffold" constructs physically emulate the glial tube - a pathway in the brain consisting of aligned astrocytes that guide the migration of neuronal progenitor cells - and therefore may facilitate directed neuronal migration for central nervous system repair. The small size and self-contained design of these aligned astrocyte constructs will permit minimally invasive transplantation in models of central nervous system injury in future studies.

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Dataset Information

Subcutaneously engineered autologous extracellular matrix scaffolds with aligned microchannels for enhanced tendon regeneration: Aligned microchannel scaffolds for tendon repair.

Publications

Subcutaneously engineered autologous extracellular matrix scaffolds with aligned microchannels for enhanced tendon regeneration: Aligned microchannel scaffolds for tendon repair.

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