Building‐Block Size Mediates Microporous Annealed Particle Hydrogel Tube Microenvironment Following Spinal Cord Injury

Author:

Ross Brian C.1ORCID,Kent Robert N.1,Saunders Michael N.1,Schwartz Samantha R.1,Smiley Brooke M.1,Hocevar Sarah E.12,Chen Shao‐Chi1,Xiao Chengchuan3,Williams Laura A.1,Anderson Aileen J.456ORCID,Cummings Brian J.456ORCID,Baker Brendon M.17ORCID,Shea Lonnie D.127ORCID

Affiliation:

1. Department of Biomedical Engineering University of Michigan 2200 Bonisteel Blvd Ann Arbor MI 48109 USA

2. Neuroscience Graduate Program University of Michigan Medical School 204 Washtenaw Ave Ann Arbor MI 48109 USA

3. Department of Molecular Cellular, and Developmental Biology University of Michigan 1105 North University Ave Ann Arbor MI 48109 USA

4. Institute for Memory Impairments and Neurological Disorders University of California Biological Sciences III, 2642 Irvine CA 92697 USA

5. Sue and Bill Gross Stem Cell Research Center University of California 845 Health Sciences Rd Irvine CA 92697 USA

6. Physical Medicine and Rehabilitation University of California 18124 Culver Dr # F Irvine CA 92612 USA

7. Department of Chemical Engineering University of Michigan 2300 Hayward St Ann Arbor MI 48109 USA

Abstract

AbstractSpinal cord injury (SCI) is a life‐altering event, which often results in loss of sensory and motor function below the level of trauma. Biomaterial therapies have been widely investigated in SCI to promote directional regeneration but are often limited by their pre‐constructed size and shape. Herein, the design parameters of microporous annealed particles (MAPs) are investigated with tubular geometries that conform to the injury and direct axons across the defect to support functional recovery. MAP tubes prepared from 20‐, 40‐, and 60‐micron polyethylene glycol (PEG) beads are generated and implanted in a T9‐10 murine hemisection model of SCI. Tubes attenuate glial and fibrotic scarring, increase innate immune cell density, and reduce inflammatory phenotypes in a bead size‐dependent manner. Tubes composed of 60‐micron beads increase the cell density of the chronic macrophage response, while neutrophil infiltration and phenotypes do not deviate from those seen in controls. At 8 weeks postinjury, implantation of tubes composed of 60‐micron beads results in enhanced locomotor function, robust axonal ingrowth, and remyelination through both lumens and the inter‐tube space. Collectively, these studies demonstrate the importance of bead size in MAP construction and highlight PEG tubes as a biomaterial therapy to promote regeneration and functional recovery in SCI.

Funder

National Institute of Allergy and Infectious Diseases

National Institute of Neurological Disorders and Stroke

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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