Embedded 3D Bioprinting of tissue-engineered skin constructs

Abstract

The integumentary system, which comprises of the skin and its appendages, is the largest multi-functional organ of the human body. Skin has been an important research topic in medical and cosmetic fields, since its appearance can be an indicator or reflect several diseases and traumas. The primary challenge of treating skin wounds stem from the skin’s inability to fully repair itself after chronic wounds, and the shortcomings of existing treatment methods. Moreover, to understand the physiology of skin and its associated diseases, the gold standard is to obtain a biopsy from a patient, which is an accurate but an invasive and time-consuming procedure. Despite progress in developing biomaterials for skin equivalents and wound dressings, significant limitations persist, such as inadequate vascularisation, delayed cell infiltration, scarring, and insufficient mechanical strength. Bioprinting offers a potential solution by automatically depositing biomaterials in a three-dimensional (3D) space, with a freedom of design by user to create skin constructs for both in vitro and in vivo uses. This thesis addresses several obstacles in 3D skin bioprinting and presents the pertinent aspects of design, characterisation and fabrication of an embedded 3D bioprinted skin constructs using tissue engineering and additive manufacturing. It demonstrates that tissue engineering constructs using low-viscosity hydrogels, printed in a support bath, can achieve both high printing precision and cell viability essential for functionality without compromise. A comprehensive literature review highlights recent advances in skin tissue engineering, biomaterials, and additive manufacturing. The thesis employs a supportive gel bed (Carbopol 980) to layer cell/hydrogel mixtures, preserving construct shape until solidification. Distinct biomaterials are characterised and optimised for multilayer, multimaterial printing within the Carbopol 980 bath, overcoming traditional limitations of printing low-viscosity solutions onto flat surfaces. This technique has enabled the bioprinting of a skin equivalent with chronic-depth characteristics, including a hypodermis, a dual-compartment dermis, and an epidermis. The resulting construct featured gradients in material properties, mechanical characteristics, microarchitecture, skin ECM generation and cell type gradients, serving as an example of the system's capability to generate sophisticated human tissue. This research demonstrates the promise of a support bath assisted biofabrication strategy for supporting the formation of skin-like structures in vitro, including distinct dermal and epidermal compartments with characteristics resembling human skin, for applications in skin tissue engineering

Date of Award	1 Aug 2025
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Paul Mativenga (Supervisor) & Amaya Viros Usandizaga (Supervisor)