Effect of Collagen Nanotopography on Keloid Fibroblast Proliferation and Matrix Synthesis: Implications for Dermal Wound Healing

Abstract

Keloids are locally exuberant dermal scars characterized by excessive fibroblast proliferation and matrix accumulation. Although treatment strategies include surgical removal and intralesional steroid injections, an effective regimen is yet to be established due to a high rate of recurrence. The regressing center and growing margin of the keloid have different collagen architecture and also differ in the rate of proliferation. To investigate whether proliferation is responsive to collagen topography, keloid, scar, and dermal fibroblasts were cultured on nanopatterned scaffolds varying in collagen fibril diameter and alignment-small and large diameter, aligned and random fibrils, and compared to cells grown on flat collagen-coated substrates, respectively. Cell morphology, proliferation, and expression of six genes related to proliferation (cyclin D1), phenotype (asmooth muscle actin), and matrix synthesis (collagens I and III, and matrix metalloproteinase-1 and -2) were measured to evaluate cell response. Fibril alignment was shown to reduce proliferation and matrix synthesis in all three types of fibroblasts. Further, keloid cells were found to be most responsive to nanotopography.

Multi‐dimensional models for functional testing of keloid scars: In silico, in vitro, organoid, organotypic, ex vivo organ culture, and in vivo models

“…Simple organotypic keloid models involve the culturing of keloid derived fibroblasts in bovine/rat type I collagen matrices, without any epidermal keratinocytes. Such collagen‐derived dermal scaffolds can range from simple layer of collagen to nano‐patterned collagen matrices populated with dermal fibroblasts . A vast body of research community has dedicated their time into development of such organotypic skin models over the past years, therefore we will explore just a few of those studies.…”

Comprehensive Review of Keloid Formation

“…In addition, these cells have higher rates of mitosis, and lower rates of apoptosis. [6,9,10,11] There are several theories of keloid formation according to induced factor. Some of them implicate certain cytokines, other implicate keratinocyte.…”

“…Keloid lesions were found to have lower rates of apoptosis than normal skin, because downregulation of apoptosis-related genes, including p53 [6,9,11,17].…”

The role of Duffy antigen receptor for chemokines in keloids

“…The pathogenesis of keloids has been related to the alterations in cell proliferation and migration, synthesis and secretion of extracellular matrix proteins, and inflammatory responses (Machesney et al, 1998;Tredget et al, 1997;Muthusubramaniam et al, 2014). Cytokines and chemokines have been involved in various tissue-specific inflammatory events, cancer metastasis, and fibrosis.…”