Development of bioactive catechol functionalized nanoparticles applicable for 3D bioprinting

Autor: Małgorzata K. Włodarczyk-Biegun, Aránzazu del Campo, María Puertas-Bartolomé, Julio San Román, Blanca Vázquez-Lasa
Přispěvatelé: Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), Consejo Superior de Investigaciones Científicas (España)
Rok vydání: 2021
Předmět:
Zdroj: Materials scienceengineering. C, Materials for biological applications. 131
ISSN: 1873-0191
Popis: Efficient wound treatments to target specific events in the healing process of chronic wounds constitute a significant aim in regenerative medicine. In this sense, nanomedicine can offer new opportunities to improve the effectiveness of existing wound therapies. The aim of this study was to develop catechol bearing polymeric nanoparticles (NPs) and to evaluate their potential in the field of wound healing. Thus, NPs wound healing promoting activities, potential for drug encapsulation and controlled release, and further incorporation in a hydrogel bioink formulation to fabricate cell-laden 3D scaffolds are studied. NPs with 2 and 29 M % catechol contents (named NP2 and NP29) were obtained by nanoprecipitation and presented hydrodynamic diameters of 100 and 75 nm respectively. These nanocarriers encapsulated the hydrophobic compound coumarin-6 with 70% encapsulation efficiency values. In cell culture studies, the NPs had a protective effect in RAW 264.7 macrophages against oxidative stress damage induced by radical oxygen species (ROS). They also presented a regulatory effect on the inflammatory response of stimulated macrophages and promoted upregulation of the vascular endothelial growth factor (VEGF) in fibroblasts and endothelial cells. In particular, NP29 were used in a hydrogel bioink formulation using carboxymethyl chitosan and hyaluronic acid as polymeric matrices. Using a reactive mixing bioprinting approach, NP-loaded hydrogel scaffolds with good structural integrity, shape fidelity and homogeneous NPs dispersion, were obtained. The in vitro catechol NPs release profile of the printed scaffolds revealed a sustained delivery. The bioprinted scaffolds supported viability and proliferation of encapsulated L929 fibroblasts over 14 days. We envision that the catechol functionalized NPs and resulting bioactive bioink presented in this work offer promising advantages for wound healing applications, as they: 1) support controlled release of bioactive catechol NPs to the wound site; 2) can incorporate additional therapeutic functions by co-encapsulating drugs; 3) can be printed into 3D scaffolds with tailored geometries based on patient requirements.
Authors thank CIBER-BBN (Spain) and the Spanish Ministry of Economy and Competitivity (M. Puertas-Bartolomé scholarship BES-2015-075161) and the Spanish Ministry of Science and Innovation (PID2020-114086RB-100) for supporting this work. The authors acknowledge RegenHu company, and particularly: Sandro Figi, Dominic Ernst, Michael Kuster and Andreas Scheidegger, for the fruitful collaboration, development and providing the mixing tool. The authors thank Dr. Emmanuel Terriac from INM, Germany for assistance in the confocal imaging. B. Vázquez-Lasa is a member of the SusPlast platform from CSIC
Databáze: OpenAIRE