Creation of a Large Adipose Tissue Construct in Humans Using a Tissue-engineering Chamber: A Step Forward in the Clinical Application of Soft Tissue Engineering

Abstract

Tissue engineering is currently exploring new and exciting avenues for the repair of soft tissue and organ defects. Adipose tissue engineering using the tissue engineering chamber (TEC) model has yielded promising results in animals; however, to date, there have been no reports on the use of this device in humans. Five female post mastectomy patients ranging from 35 to 49years old were recruited and a pedicled thoracodorsal artery perforator fat flap ranging from 6 to 50ml was harvested, transposed onto the chest wall and covered by an acrylic perforated dome-shaped chamber ranging from 140 to 350cm(3). Magnetic resonance evaluation was performed at three and six months after chamber implantation. Chambers were removed at six months and samples were obtained for histological analysis. In one patient, newly formed tissue to a volume of 210ml was generated inside the chamber. One patient was unable to complete the trial and the other three failed to develop significant enlargement of the original fat flap, which, at the time of chamber explantation, was encased in a thick fibrous capsule. Our study provides evidence that generation of large well-vascularized tissue engineered constructs using the TEC is feasible in humans.

Keywords: Adipose; Adipose-derived stem cells; Chamber; Inflammation; Soft tissue reconstruction; Tissue engineering.

Fig. 1

Chamber and surgical procedure. (A) Acrylic 210 cm³ chamber with notch on one side to allow for pedicle passage. (B) Preoperative markings of thoracodorsal artery perforators and TAP flap design in patient 2. Tissue expander in place post right mastectomy. (C) Harvested fat flap approximately 30 ml based on thoracodorsal system. (D) Flap transposed onto chest wall with dome shaped chamber placed on top.

Fig. 2

Intraoperative view upon chamber removal of patient 2. The 210 ml space is entirely filled with tissue. (A) Oblique lateral view. (B) Frontal view.

Fig. 3

Detail of tissue generated in patient 2 showing adipose tissue under fibrous capsule in the lateral aspect.

Fig. 4

Patient 2 after chamber removal. (A) Immediate postoperative result. (B) Six months follow-up. Newly grown tissue remained stable and had softened to a “fat-like” consistency.

Fig. 5

(A) Specimen excised from patient 3 after formalin fixation. Note that in spite of early chamber removal (7 weeks), approximately a four-fold increase in tissue volume is observed. (B) Histological analysis showing viable adipose tissue as demonstrated by perilipin staining.

Fig. 6

Intraoperative view upon chamber removal of patient 4. After removing the chamber, the space was empty, being fluid filled only, and the fat flap was seen to be encased in a thick fibrotic capsule without signs of enlargement (A). After capsulectomy, a healthy normal-looking adipose tissue flap was observed (B).

Fig. 7

Histological analysis of encased fat excised in patient 4. (A) Perilipin staining confirms viability of adipose tissue under the fibrous capsule. (B) CD31 staining shows adipocytes surrounding perfused blood vessels.