Transformation of Breast Reconstruction via Additive Biomanufacturing

Mohit P Chhaya,Dietmar W Hutmacher,Jan-Thorsten Schantz,Elizabeth R Balmayor

doi:10.1038/srep28030

Abstract

Adipose tissue engineering offers a promising alternative to current breast reconstruction options. However, the conventional approach of using a scaffold in combination with adipose-derived precursor cells poses several problems in terms of scalability and hence clinical feasibility. Following the body-as-a-bioreactor approach, this study proposes a unique concept of delayed fat injection into an additive biomanufactured and custom-made scaffold. Three study groups were evaluated: Empty scaffold, Scaffold containing 4 cm3 lipoaspirate and Empty scaffold +2-week prevascularisation period. In group 3, of prevascularisation, 4 cm3 of lipoaspirate was injected into scaffolds after 2 weeks. Using a well-characterised additive biomanufacturing technology platform, patient-specific scaffolds made of medical-grade-polycaprolactone were designed and fabricated. Scaffolds were implanted in subglandular pockets in immunocompetent minipigs (n = 4) for 24-weeks. Angiogenesis and adipose tissue regeneration were observed in all constructs. Histological evaluation showed that the prevascularisation + lipoaspirate group had the highest relative area of adipose tissue (47.32% ± 4.12) which was significantly higher than both lipoaspirate-only (39.67% ± 2.04) and empty control group (8.31% ± 8.94) and similar to native breast tissue (44.97% ± 14.12). This large preclinical animal study provides proof-of-principle that the clinically applicable prevascularisation and delayed fat-injection techniques can be used for regeneration of large volumes of adipose tissue.

Highlights

Breast cancer is a major cause of illness for women, with an estimated number of 300,000 new cases diagnosed in 20131,2
In order to solve the problems of vascularisation and adipose tissue remodelling in the field of breast tissue engineering, we have devised a unique concept based on the combination of an additive biomanufactured and patient-specific biodegradable scaffold in combination with a delayed fat injection
It is well known in the literature that the fibrin network and the associated growth-factor cocktail stimulates a strong angiogenic response and induce highly organised connective tissue to penetrate into the affected region[21,22]

Summary

Introduction

Breast cancer is a major cause of illness for women, with an estimated number of 300,000 new cases diagnosed in 20131,2. In order to solve the problems of vascularisation and adipose tissue remodelling in the field of breast tissue engineering, we have devised a unique concept based on the combination of an additive biomanufactured and patient-specific biodegradable scaffold in combination with a delayed fat injection. In this method of implantation, a scaffold additive biomanufactured from medical grade polycaprolactone (mPCL) is first implanted into the implantation site. We further hypothesise that the presence of a pre-formed bed of connective tissue and vasculature would allow the injected fat to remodel within the highly porous scaffold architecture with minimal tissue necrosis and graft resorption

Methods

Results

Conclusion