Preadipocyte-Derived Decellularized Extracellular Matrix-Functionalized Three Dimensionally Printed Scaffolds Regulate Vascularized Adipose Tissue Regeneration via Modulation of Selected Paracrine Factors.

Authors

Danling Wang, Xiao Liu, Hengyuan Zhang, Zilong Xu, Zhikai Tan

Published in

ACS applied materials & interfaces. Nov 13, 2026. Epub Nov 13, 2026.

Abstract

The clinical efficacy of soft tissue reconstruction is severely hindered by unpredictable graft resorption and inadequate vascularization. Traditional synthetic implant scaffolds offer mechanical support, with limited bioactivity for adipose tissue regeneration. In this study, we developed a "three-in-one" bioinstructive platform (dPCL) integrating structural support, signal induction, and immunomodulation by functionalizing a 3D-printed polycaprolactone (PCL) framework with a decellularized extracellular matrix (dECM) derived from 3T3-L1 preadipocytes. The obtained dECM-functionalized scaffold provided essential biochemical cues. In vitro assays demonstrated that dPCL significantly enhanced preadipocyte adhesion and adipogenic differentiation. Besides, the dECM-functionalized scaffold was found to modulate the secretion of selected paracrine factors, markedly upregulating the secretion of adiponectin, VEGF, and IL-10, which facilitated cell differentiation and robust endothelial network formation. In vivo evaluation in a murine subcutaneous model confirmed that dPCL scaffolds effectively supported the formation of stable, well-vascularized adipose tissue. Furthermore, the dECM-functionalized scaffold enhanced the recruitment and accumulation of proregenerative M2 macrophages, maintaining an M2-dominant tissue microenvironment that facilitated graft integration. In summary, current findings demonstrate that integrating cell-specific dECM with 3D-printed scaffolds creates a multifaceted bioactive platform that overcomes the critical barriers of vascularization and metabolic integration, presenting a highly promising strategy for functional soft tissue regeneration.

PMID:
43023726
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.

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