Abstract
For individuals undergoing mastectomy, reconstruction of the nipple–areola complex (NAC) is a critical step in emotional and psychological recovery. However, current clinical approaches— including flap suturing, tattooing, or grafting—are limited by loss of projection, poor mechanical stability, and absence of sensation. Additive manufacturing and tissue engineering offer promising alternatives by enabling the development of hybrid scaffolds that maintain long-term projection and support the potential return of sensation.
Recent research has focused on NAC tissue engineering, aiming to fabricate biomimetic architectures that replicate native anatomy and function while promoting tissue integration and mechanical stability. However, an adequately tissue engineered innervated NAC has yet to be achieved, highlighting the need for further research to develop clinically viable constructs. The current project aims to develop a hybrid tissue engineered NAC scaffold that can not only maintain long-term nipple projection but grow multiple cell types to enable multifunctional tissue regeneration.
A dual-scale, multi-material hybrid scaffold was developed to recapitulate the structural and functional complexity of a biomimetic NAC. A non-thermal plasma treated, melt extruded polycaprolactone (PCL) scaffold was explored to support long-term projection in NAC reconstruction, leveraging the combined advantages of three-dimensional (3D) printing and surface modification to produce a bioactive construct with high structural integrity. In parallel, an electrospun poly(vinyl alcohol) PVA/PEDOT:PSS scaffold was investigated to incorporate conductive polymers within extracellular matrix (ECM)-like fibres, enhancing cell adhesion and promoting neural proliferation and maturation. The integration of these complementary approaches addresses key limitations associated with single-method scaffold design. Plasma treatment significantly enhanced the hydrophilicity, collagen immobilisation and HaCaT cell adhesion of the melt extruded PCL scaffold, while preserving structural integrity and favourable in vitro degradation behaviour. The electrospun PVA/PEDOT:PSS scaffold was optimised to yield defect-free fibres; however, MTT analysis indicated cell viability below 70%, suggesting the need for alternative, more biocompatible counterions for PEDOT polymerisation.
Collectively, these findings highlight the potential of combining advances in biomaterials science, regenerative medicine, and advanced fabrication technologies to progress toward nipple reconstructions that are not only structurally and aesthetically biomimetic, but also biologically responsive and capable of sensory function.