Abstract
In patients with comorbidities, a large number of wounds become chronic, representing an overwhelming economic burden for healthcare systems. Engineering the microenvironment is a paramount trend to activate cells and burst-healing mechanisms. The extrusion bioprinting of advanced dressings was performed with novel composite bioinks made by blending adipose decellularized extracellular matrix with plasma and human dermal fibroblasts. Rheological and microstructural assessments of the composite hydrogels supported post-printing cell viability and proliferation over time. Embedded fibroblasts expressed steady concentrations of extracellular matrix proteins, including type 1, 3 and 4 collagens and fibronectin. ELISA assessments, multiplex protein arrays and ensuing bioinformatic analyses revealed paracrine activities corresponding to wound-healing activation through the modulation of inflammation and angiogenesis. The two modalities of advanced dressings, differing in platelet number, showed differences in the release of inflammatory and angiogenic cytokines, including interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conditioned media stimulated human-dermal-cell proliferation over time. Our findings open the door to engineering the microenvironment as a strategy to enhance healing.
Highlights
By adding platelet-rich plasma (PRP) to bioink, we provided active biological molecules to drive cell activities towards the enrichment of healing mechanisms
The viscosity of the hybrid bioinks showed medium values compared with raw bioinks DAM2, PRP/ALG and platelet-poor plasma (PPP)/ALG
Using multiplex protein analyses, followed by data analyses by means of cloud-based software (QIAGEN Ingenuity Pathway Analysis (IPA)®, Redwood City, CA; USA), we found that dermal cells embedded within the bioprinted dressings synthesized and released, over time, a large pool of signaling proteins involved in the canonical wound-healing pathway (Figure 1)
Summary
Skin is the first line of defense against many types of infections and diseases. In healthy people, repair through a sequence of complex, constitutively active signaling pathways. In patients with comorbidities, a large number of wounds become chronic as they fail to repair within three months [1]. Venous stasis, radiation or paralyses are common risk factors for complex wounds. In these patients, healing mechanisms fail to progress through the different stages and ulcers become stagnant. Wound chronicity, referred to as silent epidemic, is an overwhelming economic and medical burden for healthcare systems [2,3]. Common biological features of chronicity include uncontrolled inflammation and loss of the dermal cells’ ability to respond to reparative stimuli [4]
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