# 3D Printing of Oxygen-Sensing ECM-Based Skin Graft for Personalized Treatment of Chronic Wounds—A Technological Proof of Concept

## TL;DR

This paper introduces a 3D-printed skin graft with oxygen sensors to help treat chronic diabetic wounds by monitoring and improving healing conditions.

## Contribution

A novel 3D-printed, oxygen-sensing extracellular matrix-based skin graft for personalized treatment of chronic wounds is developed and tested.

## Key findings

- A porcine skin decellularization protocol was developed, preserving ECM integrity while removing cellular components.
- 3D bioprinted grafts with embedded oxygen sensors showed cytocompatibility and low immunogenicity in in vitro and in vivo studies.
- The grafts can be tailored to individual wound geometries, enabling personalized treatment approaches.

## Abstract

Chronic diabetic wounds are often characterized by persistent hypoxia and poor healing outcomes, highlighting the need for regenerative grafts that not only promote tissue repair but also provide insights into the wound microenvironment. In this study, we introduce a novel strategy for diabetic ulcer treatment through the development of a structurally personalized skin graft. The graft is fabricated via 3D bioprinting of natural porcine skin extracellular matrix (psECM) and integrated with microsensors for oxygen monitoring. We established a porcine skin decellularization protocol that efficiently removed cellular components, while preserving the integrity of the ECM, as verified by DNA quantification and scanning electron microscopy. The resulting psECM bioink demonstrated rheological properties suitable for 3D printing, which depended on psECM concentration and exhibited temperature-responsive gelation behavior. Incorporation of LiNC-BuO oxygen microsensors into the bioink enabled real-time, non-invasive oxygen level monitoring within the printed constructs. Both in vitro and in vivo studies confirmed the cytocompatibility and low immunogenicity of the psECM-based grafts with embedded microsensors. Moreover, the 3D bioprinting technology enabled the manufacturing of grafts tailored to match individual wound geometries. The technological proof of concept presented herein for this multifunctional platform, which integrates the regenerative benefits of ECM scaffolds with advanced biosensing capabilities, represents a promising approach for enhancing future therapeutic outcomes in the management of diabetic ulcers.