Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractControlling the cell-substrate interactions at the bio-interface is becoming an inherent element in the design of implantable devices. Modulation of cellular adhesion in vitro, through topographical cues, is a well-documented process that offers control over subsequent cellular functions. However, it is still unclear whether surface topography can be translated into a clinically functional response in vivo at the tissue / device interface. Herein, we demonstrated that anisotropic substrates with a groove depth of ~317 nm and ~1,988 nm promoted human tenocyte alignment parallel to the underlying topography in vitro. However, the rigid poly(lactic-co-glycolic acid) substrates used in this study upregulated the expression of chondrogenic and osteogenic genes, indicating possible tenocyte trans-differentiation. Of significant importance is that none of the topographies assessed (~37 nm, ~317 nm and ~1,988 nm groove depth) induced extracellular matrix orientation parallel to the substrate orientation in a rat patellar tendon model. These data indicate that two-dimensional imprinting technologies are useful tools for in vitro cell phenotype maintenance, rather than for organised neotissue formation in vivo, should multifactorial approaches that consider both surface topography and substrate rigidity be established.

The characterization of decellularized human skeletal muscle as a blueprint for mimetic scaffolds

“…In-vitro models indicate that muscle progenitor cells utilize alignment cues during myogenesis [51, 52]. Similar alignment-sensitive responses have been reported for other cells, including cardiac muscle and tendons [53, 54]. Yet, while the many in-vitro alignment studies support the motivation of aligned regenerative scaffolds, we recognize that in-vivo evidence indicating that scaffold alignment is critical to muscle implant success does not exist.…”

Nanostructured scaffold as a determinant of stem cell fate

“…This indicates that cell phenotype maintenance is well established by two-dimensional (2D) imprinting technologies only in an in vitro condition. In an in vivo scenario, the neotissue formation and organization is established by multiple factors [40]. Another study deciphered the 2D imprinting technique exclusively to assess cell function in vitro for phenotype maintenance of human primary osteoblast phenotype on substrates of different grooves.…”

Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

“…39,40 Similar alignment-sensitive responses have been reported for other cells, including cardiac muscle and tendons. 41,42 Yet, while the many in vitro alignment studies support the motivation of aligned regenerative scaffolds, we recognize that in vivo evidence indicating that scaffold alignment is critical to muscle implant success does not yet exist. The lack of in vivo data supporting the importance of scaffold alignment in muscle regenerative therapies would appear to motivate future studies.…”