Subpopulations of dermal skin fibroblasts secrete distinct extracellular matrix: implications for using skin substitutes in the clinic

Abstract

SummaryBackgroundWhile several commercial dermoepidermal scaffolds can promote wound healing of the skin, the achievement of complete skin regeneration still represents a major challenge.ObjectivesTo perform biological characterization of self‐assembled extracellular matrices (ECMs) from three different subpopulations of fibroblasts found in human skin: papillary fibroblasts (Pfi), reticular fibroblasts (Rfi) and dermal papilla fibroblasts (DPfi).MethodsFibroblast subpopulations were cultured with ascorbic acid to promote cell‐assembled matrix production for 10 days. Subsequently, cells were removed and the remaining matrices characterized. Additionally, in another experiment, keratinocytes were seeded on the top of cell‐depleted ECMs to generate epidermal‐only skin constructs.ResultsWe found that the ECM self‐assembled by Pfi exhibited randomly oriented fibres associated with the highest interfibrillar space, reflecting ECM characteristics that are physiologically present within the papillary dermis. Mass spectrometry followed by validation with immunofluorescence analysis showed that thrombospondin 1 is preferentially expressed within the DPfi‐derived matrix. Moreover, we observed that epidermal constructs grown on DPfi or Pfi matrices exhibited normal basement membrane formation, whereas Rfi matrices were unable to support membrane formation.ConclusionsWe argue that inspiration can be taken from these different ECMs, to improve the design of therapeutic biomaterials in skin engineering applications.

Solution Blow Spinning of Polycaprolactone—Rheological Determination of Spinnability and the Effect of Processing Conditions on Fiber Diameter and Alignment

“…Biodegradable polymer mats made from randomly aligned fibers structurally similar to the native ECM of, e.g., skin or bone tissue [ 16 , 17 , 18 , 19 ] or highly aligned fibers characteristic for the anisotropic structure of, e.g., nervous or myocardial muscle tissue [ 20 , 21 , 22 , 23 , 24 ] can be successfully produced using the solution blow spinning (SBS) method with controlled process parameters, as shown in this study. Solution blow spinning is a relatively novel method for the production of submicron polymer fibers, currently gaining significant interest as a rapid, safe, and attractive alternative to the decades-old, widely used electrospinning [ 25 , 26 , 27 ].…”

Human Organ-Specific 3D Cancer Models Produced by the Stromal Self-Assembly Method of Tissue Engineering for the Study of Solid Tumors

“…Under stress conditions, fibroblasts adapt to their environment and have the ability to send local signals, to synthesize and reorganize the ECM of the skin and other organs [10,11]. Fibroblast plasticity may be different depending on body parts, through a poorly understood mechanism involving the resident ECM framework and the microenvironment [12]. In certain pathological contexts, fibroblasts are capable of altering their cellular profile to become myofibroblasts, therefore producing massive amounts of ECM and contributing to organ dysfunction [13].…”

Utilizing Human Dermal Fibroblast Heterogeneity in Autologous Dermal Fibroblast Therapy: An Overcomplicated Strategy or a Promising Approach?

“…Therefore, DF heterogeneity was recognized as a possible mechanism of hypertrophic scarring (Wang et al, 2008;Varkey et al, 2011;Zuo et al, 2016 ;Zuo and Lu, 2017). Moreover, DF heterogeneity also has implications for wound healing (Kaminishi-Tanikawa et al, 2011;Woodley, 2017;Stunova and Vistejnova, 2018) and skin tissue engineering (Mine et al, 2008;Varkey et al, 2011;Sriram et al, 2015;Ghetti et al, 2018).…”