Polymer fiber-based models of connective tissue repair and healing

Abstract

Physiologically relevant models of wound healing are essential for understanding the biology of connective tissue repair and healing. They can also be used to identify key cellular processes and matrix characteristics essential for the design of soft tissue grafts. Modeling the various stages of repair post tendon injury, polymer meshes of varying fiber diameter (nano-1 (390 nm) < nano-2 (740 nm) < micro (1420 nm)) were produced. Alignment was also introduced in the nano-2 group to model matrix undergoing biological healing rather than scar formation. The response of human tendon fibroblasts on these model substrates were evaluated over time as a function of fiber diameter and alignment. It was observed that the repair models of unaligned nanoscale fibers enhanced cell growth and collagen synthesis, while these outcomes were significantly reduced in the mature repair model consisting of unaligned micron-sized fibers. Organization of paxillin and actin on unaligned meshes was enhanced on micro-compared to nano-sized fibers, while the expression and activity of RhoA and Rac1 were greater on nanofibers. In contrast, aligned nanofibers promoted early cell organization, while reducing excessive cell growth and collagen production in the long term. These results show that the early-stage repair model of unaligned nanoscale fibers elicits a response characteristic of the proliferative phase of wound repair, while the more mature model consisting of unaligned micron-sized fibers is more representative of the remodeling phase by supporting cell organization while suppressing growth and biosynthesis. Interestingly, introduction of fiber alignment in the nanofiber model alters fibroblast response from repair to healing, implicating matrix alignment as a critical design factor for circumventing scar formation and promoting biological healing of soft tissue injuries.

Living nanofiber yarn-based woven biotextiles for tendon tissue engineering using cell tri-culture and mechanical stimulation

“…4A, 5A, 6A and 7A). As supported by prior studies, our findings confirm that aligned topography guides cell alignment and organization, and introduces the collagen formation along the arrangement direction of fibers [27, 57, 58]. …”

3D Mimicry of Native‐Tissue‐Fiber Architecture Guides Tendon‐Derived Cells and Adipose Stem Cells into Artificial Tendon Constructs

“…[4a,18] Accordingly, there are increasing evidences on the strong relationship between fibrous substrate topography and the global cell function after T/L injury. Recent studies suggest that fiber diameter and alignment might either direct the cell response toward the characteristic proliferative phase of wound repair resulting in scar tissue formation (random micron scale fibers), or in contrast, direct cell into a behavior indicative of normal healing response, leading to tissue regeneration (aligned submicron fibers) . Therefore, scaffold for T/L TE should ideally combine a range of tissue‐specific architectural, topographical, and biochemical characteristics that provide the necessary microenvironment to guide cells into a tenogenic behavior, and result in constructs that can support the biomechanical demands of native tissues upon transplantation.…”

Polymeric mesh and insulin‐like growth factor 1 delivery enhance cell homing and graft−cartilage integration

“…Before imaging, the samples were sputter‐coated (Cressington 108auto) with gold‐palladium (10 s, 2 nm) to reduce charging effects. Fiber diameter ( n = 3 meshes/group, 20−30 fibers per mesh) was quantified via analysis of SEM micrographs using ImageJ (National Institutes of Health) …”