Sustained regeneration of high-volume adipose tissue for breast reconstruction using computer aided design and biomanufacturing

Chhaya, Mohit P.; Melchels, Ferry P.W.; Holzapfel, Boris Michael; Baldwin, Jeremy; Hutmacher, Dietmar W.

doi:10.1016/j.biomaterials.2015.01.025

Cited by 97 publications

(79 citation statements)

References 54 publications

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“…Non-specific localised low-grade granulomatose reactions were observed in the vicinity of the localised scaffold strands, consistent with previous reports30. A granuloma is an organised collection of macrophages46.…”

Section: Discussionsupporting

confidence: 91%

“…Therefore, a defect filled with immature tissue should not be considered as “regenerated”. In keeping with this paradigm, our previously undertaken small animal study38 as well as the presented study has indicated that a scaffold made out slow-degrading polymer such as mPCL allows to maintain the mechanical properties for a sufficient period of time for large volume adipose tissue not only to show signs of regeneration but also to remodel at least twice and therefore present a mature tissue hemostasis at the time the scaffold shows any signs of mechanical degradation and/or mass loss.…”

Section: Discussionmentioning

confidence: 52%

“…The presented study was based on a foundation of previous small animal studies and clinical observations3058 and provided proof of principle that the prevascularisation and delayed fat injection techniques can be used for efficient regeneration of large volumes of adipose tissue for long periods of time. This work provides an important validation point for the regeneration of clinically relevant volumes of vascular-rich tissues in post-mastectomy breast reconstruction surgeries paving the way for future human clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…Previous long-term rodent studies performed in our laboratory have shown sustained regeneration of high volumes of fat using cell-seeded anatomically shaped scaffolds30. These cell-based approaches have merit from a tissue engineering perspective; however, from a clinically driven regenerative medicine point of view they also have disadvantages with problems ranging from scaling up of tissue culture protocols and associated costs and regulatory hurdles.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, the combined area of the tissue section was measured (C). The ratio of adipose tissue area to total tissue area (R) was calculated using the following formula30:…”

Section: Methodsmentioning

confidence: 99%

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Transformation of Breast Reconstruction via Additive Biomanufacturing

Chhaya

Balmayor

Hutmacher

et al. 2016

Sci Rep

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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.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Finally, the combined area of the tissue section was measured (C). The ratio of adipose tissue area to total tissue area (R) was calculated using the following formula30:…”

Section: Methodsmentioning

confidence: 99%

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