New horizons for breast reconstruction 

By Themis Halka

Breast cancer is the most common type of cancer in females, affecting 1 in 8 women in the UK.¹ Several treatment options are available, including radiotherapy, chemotherapy, hormone therapy, and surgery. Surgery currently remains extensively used, either alone or in combination. Two such surgical procedures are available depending on the type and stage of cancer. Mastectomy consists in the removal of the whole breast, including the nipple, while breast conservative surgery, or lumpectomy, aims to remove the tumour cells only, leaving healthy breast tissues intact.¹ In both cases, women will lose either a part or the whole of their breast. 

Several options for breast reconstruction are currently available on the market. Breast implants, silicon- or saline-based, enable patients to recover their breast shape. The texture, sensation and comfort of these implants is limited, as silicone does not present the softness and elasticity of human tissue.² The main challenge with such implants is their limited lifespan, requiring a replacement approximately every 10 years, or even less in case of rupture of the implant or other associated problems. This represents a constraint for patients who engage in this solution, as they will need to change implants for on average 2-4 times in their lifetime, each time enduring surgery and its complications. The implants’ risks for human health also discourage many from choosing this option, especially since the 2010 PIP scandal, where presumed health-threatening implants had to be removed from patients.³

The field of breast reconstruction needs to widen its reach and offer solutions that fit patients’ needs in terms of safety, comfort, aesthetics, and convenience. Today, it has been estimated that only a third of women who underwent breast surgery chose breast reconstruction.¹ Other reconstruction methods that have been developed and offer a potential alternative to breast implants also have serious drawbacks. Autologous fat grafting (AFG) involves ex vivo procedures, whereby fat cells that have been previously harvested from patient are returned through injection into the breast tissue (lipofilling), after treatment and processing .⁴ This allows addition of self-tissue, solving the issues of biocompatibility and toxicity of breast implants. However, AFG is limited by fat resorption (25-80%) and is generally poorly taken into tissues. This might arise from the lack of tissue organisation and vascularisation in the injected fat, which does not promote proliferation due to the absence of appropriate structural support and oxygen supply.⁴

In order to tackle this challenge, it has been suggested that providing a scaffold could help the integration of the AFG into tissues. Among other companies, BellaSeno is working on printing a bioresorbable scaffold that would be implanted into the breast, and then injected with lipofilling.⁵ This scaffold would provide support for cell expansion, thanks to its specific porous architecture enabling adipogenesis (proliferation of fat cells) and vascularisation (creation of blood vessels).⁵ Adipocytes previously harvested would be injected in the porous matrix, and gradually colonise the structure, restoring an organised tissue, with the development of a vasculature and extracellular matrix. In addition to this first innovation, they implemented a bioresorbable scaffold that would be gradually degraded by the human body in 18 months, ensuring the presence of a foreign body is only transitory as opposed to breast implants.⁵ In terms of material, BellaSeno relies on polycaprolactone, a biopolymer that presents appropriate mechanical properties (elasticity, softness, resistance),^2,5 ensuring maintenance of the breast shape while conserving a soft tissue close to that of human. The company ultimately hopes to achieve breast self-tissue regeneration via one unique surgery and more biocompatible materials.

Focusing on the interesting properties of hydrogels, another company, Volumina, has developed the AdiPearl technology, which also aims for breast tissue regeneration through the appropriate architecture provided by the gel.⁶Volumina is developing a cryogel, an innovation that would allow implantation of the scaffold into the breast via simple injection, thanks to the shape-memory and compression properties of the material. The structure would be dehydrated, compressed into the syringe, and regain its initial form once rehydrated in the patient’s breast.⁶ This would be a further step towards simplifying the surgical procedure, making it less daunting and reducing the associated risks for patients. 

The last currently available option for breast reconstruction is the flap, which consists in taking a portion of tissue in one part of the body (e.g. the back), comprising skin, fat, and importantly blood vessels, and inserting it in the breast.⁷As opposed to AFG, there is no problem of resorption, as the flap is well integrated into the tissue. Vascularisation, as well as the existing tissue organisation, facilitate taking of the graft.⁷ The major issue with the flap technique is the big amount of tissue that needs to be removed from another part of the body, damaging yet another area. 

To face this issue, Lattice Medical has decided to develop a technique to achieve breast reconstruction through a smaller flap, keeping the benefits of the technique while preserving the body from excessive damage.⁸ They developed a cage, made in a biopolymer, into which the vascularised adipose flap would be inserted. As with the previous technologies mentioned, the cage would support tissue regeneration before resorbing, allowing patients to regenerate their own tissue. The cage would ensure conservation of the desired breast shape, allowing cells to colonise the whole of the structure, proliferating from the flap in an organised fashion.⁸

Overall, the field of breast reconstruction is quickly expanding, with new technologies aiming to achieve more natural breast reconstructions, in adequation to patients’ needs. Breast reconstruction could in ten years allow for restoration of shape, volume and sensation of the breast, with significantly reduced levels of associated complications. However, even if aesthetics of the breast can be restored via reconstruction, it remains for now impossible to restore breast function, as current techniques don’t allow reconstruction of organised tissues such as complex mammary glands. 

References:

1. NHS, Breast cancer in women – Treatment. Last reviewed in October 2019. Available at: https://www.nhs.uk/conditions/breast-cancer/treatment/ [Accessed on 5/10/22]
2. Reddy MSB, Ponnamma D, Choudhary R, Sadasivuni KK. A Comparative Review of Natural and Synthetic Biopolymer Composite Scaffolds. Polymers (Basel). 2021 Mar 30;13(7):1105. doi: 10.3390/polym13071105.
3. Martindale V, Menache A. The PIP scandal: an analysis of the process of quality control that failed to safeguard women from the health risks. J R Soc Med. 2013 May;106(5):173-7. doi: 10.1177/0141076813480994. 
4. Hanna Luze, MD, Anna Schwarz, MSc, Sebastian Philipp Nischwitz, MD, Dagmar Kolb, PhD, Kaddour Bounab, Robert Zrim, MD, Raimund Winter, MD, Lars-Peter Kamolz, MD, Thomas Rappl, MD, Petra Kotzbeck, PhD, Autologous Fat Grafting in Reconstructive Breast Surgery: Clinically Relevant Factors Affecting the Graft Take, Aesthetic Surgery Journal, 2022. Available at: https://doi.org/10.1093/asj/sjac166
5. Chhaya MP, Melchels FP, Holzapfel BM, Baldwin JG, Hutmacher DW. Sustained regeneration of high-volume adipose tissue for breast reconstruction using computer aided design and biomanufacturing. Biomaterials. 2015 Jun;52:551-60. doi: 10.1016/j.biomaterials.2015.01.025.
6. A. Béduer, N. Piacentini, L. Aeberli, A. Da Silva, C.A. Verheyen, F. Bonini, A. Rochat, A. Filippova, L. Serex, P. Renaud, T. Braschler. Additive manufacturing of hierarchical injectable scaffolds for tissue engineering. Acta Biomaterialia Volume 76. 2018: 71-79 Available at: https://doi.org/10.1016/j.actbio.2018.05.056.
7. Goyal A, Wu JM, Chandran VP, Reed MW. Outcome after autologous dermal sling-assisted immediate breast reconstruction. Br J Surg. 2011 Sep;98(9):1267-72. doi: 10.1002/bjs.7531. Epub 2011 May 10. 
8. Faglin P, Gradwohl M, Depoortere C, Germain N, Drucbert AS, Brun S, Nahon C, Dekiouk S, Rech A, Azaroual N, Maboudou P, Payen J, Danzé PM, Guerreschi P, Marchetti P. Rationale for the design of 3D-printable bioresorbable tissue-engineering chambers to promote the growth of adipose tissue. Sci Rep. 2020 Jul 16;10(1):11779. doi: 10.1038/s41598-020-68776-8.