Benefit of coupling heparin to crosslinked collagen I/III scaffolds for human dermal fibroblast subpopulations' tissue growth

Abstract

Currently, there is a lack of models representing the skin dermal heterogeneity for relevant research and skin engineering applications. This is the first study reporting production of dermal equivalents reproducing features of papillary and reticular dermal compartments. Inspired from our current knowledge on the architecture and composition differences between the papillary and reticular dermis, we evaluated different collagen‐based porous materials to serve as scaffolds for the three‐dimensional expansion of freshly isolated papillary and/or reticular fibroblasts. The scaffolds, composed of either collagen I or collagen I and III mixtures, were prepared by lyophilization. Pore size and hydrolytic stability were controlled by crosslinking with 1‐ethyl‐3‐(3‐dimethyl aminopropyl) carbodiimide (EDC) and N‐hydroxysuccinimide (NHS) or EDC/NHS with covalently bound heparin. The evaluation of the resultant “papillary” and “reticular” dermal equivalents was based on the analysis of characteristic features of each dermal compartment, such as cell density and deposition of newly synthetized extracellular matrix components in histological sections. Crosslinking supported cell growth during dermal tissue formation independent on the fibroblast subpopulation. The presence of collagen III seemed to have some positive but non‐specific effect only on the maintenance of the mechanical strength of the scaffolds during dermal formation. Histological analyses demonstrated a significant and specific effect of heparin on generating dermal equivalents reproducing the respective higher papillary than reticular cell densities and supporting distinct extracellular matrix components deposition (three to five times more carbohydrate material deposited by papillary fibroblasts in all scaffolds containing heparin, while higher collagen production was observed only in the presence of heparin).

Heparinized Collagen Scaffolds Based on Schiff Base Bonds for Wound Dressings Accelerate Wound Healing without Scar

“…The reason may lie in the ability of LMWH to inhibit the expression of inflammatory factors such as histamine, bradykinin, and prostaglandin E . It inhibits the transcription of inflammatory cytokines and also binds to adhesion mediators expressed during inflammation, including selectins, integrins, and their receptors, thereby reducing tissue edema and promoting wound healing . LMWH can also bind to specific sites in the amino acid sequences of affinity growth factors such as FGF, EGF, and TGF-β to protect them from protease degradation and enhance their biological activity and utilization while storing cytokines and forming concentration gradients to prolong the duration of their biological effects. , LMWH can promote the re-epithelialization of wound tissue, regulate the rearrangement of regenerated collagen, and significantly improve the quality of burn wound healing .…”

Accelerated Bone Regeneration by an Astaxanthin-Modified Antioxidant Aerogel through Relieving Oxidative Stress via the NRF2 Signaling Pathway

“…Pores in the range of 75–100 μm favor the formation of tissue with unmineralized osteoid. Larger pores (>200 μm) facilitate enhanced vascularization and bone ingrowth. , In the initial stage, due to the smaller pore size and large surface area of aerogels, BMSCs quickly adhered and formed a reticulate . In the later stage, the intermediate and large pore size promote bone formation .…”

“…The swelling ratio, as an important parameter, is associated with increased cell adhesion and proliferation. 41 As shown in Figure S2A, the weight values remained stable for a long period, and the average swelling ratio is higher than 500% for four kinds of aerogels. The release behavior of ATX was monitored for 30 days in SBF at 37 °C (Figure S2C).…”

Altered Distribution and Expression of Syndecan-1 and -4 as an Additional Hallmark in Psoriasis

“…Human epidermal keratinocytes and fibroblasts cultures were established from skin specimens according to previously published procedures [ 58 ]. Keratinocytes were grown in keratinocyte growth medium (DermaLife K basal medium, (# LL-004, CELLSYSTEMS, Troisdorf, Germany) supplemented with L-Glutamine, apo-transferrin, recombinant human (rh) transforming growth factor alpha (TGF-α), rh insulin, hydrocortisone, epinephrine, bovine pituitary extract-BPE, and gentamycin/amphotericin included in the kit (DermaLife K LifeFactors kit, (# LS-1030, CELLSYSTEMS, Troisdorf, Germany).…”