Engineered Adipose Tissue Formation Enhanced by Basic Fibroblast Growth Factor and a Mechanically Stable Environment

Abstract

Engineered adipose tissue can be used in plastic and reconstructive surgery to augment soft tissue lost due to mastectomy or lumpectomy. The three-dimensional space provided by a scaffold capable of withstanding in vivo compressive forces and neovascularization may promote engineered adipose tissue formation. The objective of this study was to determine whether voluminous adipose tissue can be engineered by combining a mechanically stable environment with basic fibroblast growth factor (bFGF). Mechanical support structures, fabricated from biodegradable synthetic polymers, were placed into subcutaneous pockets of athymic mice. Human preadipocytes, containing fibrin matrix, with (group 1) or without (group 2) bFGF were injected into the space created by the support structures. Additionally, human preadipocytes containing fibrin matrix, with (group 3) or without (group 4) bFGF, were injected into subcutaneous spaces without support structures. Six weeks after implantation, the original implant volume was approximately maintained in groups 1 and 2, whereas groups 3 and 4 showed significant implant shrinkage. Adipogenesis and angiogenesis were more extensive in the group 1 than any other group. The fraction of human nuclear antigen-positive adipocytes in the implant was highest in group 1. Mouse adipocyte-specific genes were also expressed in the implants, again at the highest levels in group 1. Implanted preadipocyte apoptosis was significantly reduced in the groups treated with bFGF (groups 1 and 3) as opposed to those without (groups 2 and 4). This study demonstrates that combining a mechanically stable environment with bFGF can promote voluminous adipose tissue regeneration. This adipogenesis was likely promoted by the mechanically stable three-dimensional space, enhanced neovascularization, implanted cell survival, and host adipogenic cell migration. The method described in this study could be useful to augment adipose tissue used in plastic and reconstructive surgery.

Prevascular Structures Promote Vascularization in Engineered Human Adipose Tissue Constructs upon Implantation

“…Few studies also indicate that sue substitutes using human adipose tissue-derived mesenchymal stromal cells (ASC) may offer a future altersuch in vitro preformed vascular-like structures (or prevascular structures) are able to connect to the host vessels native to these current treatments (1,4,7,8,11). However, limited survival of in vitro-engineered adipose tissue after implantation (21,23,27,31).…”

Hybrid Adipogenic Implants from Adipose Stem Cells for Soft Tissue Reconstruction In Vivo

“…Previously, bFGF-elaborated adipose tissue pads are small (typically <10 mm in diameter). 10,17 As a scale-up, sheep preadipocytes in alginate hydrogel yielded volumetrically maintained adipose tissue with a diameter of *15 mm after in vivo implantation. 18 In the present work, transplanted human ASCs are capable of generating a 40-mm hybrid soft tissue graft with cell survival in a thin layer of cellular interface with the host, and with volumetric expansion attributable to a large acellular biomaterial core.…”

“…16 Human preadipocytes seeded in poly(L-lactic acid)-[PLLA]-reinforced polyglycolic acid (PGA) fibers yielded adipose tissue after in vivo implantation. 17 Autologous sheep preadipocytes seeded in alginate hydrogel with or without RGD modification, after in vivo implantation, generated volumetrically maintained adipose tissue, with RGDmodified alginate showing advantage for cell adhesion and proliferation. 18 Despite the above-mentioned progress in the area of adipose tissue engineering, several critical roadblocks remain, including interrelated issues of angiogenesis, scaleup, and the maintenance of anatomic shape and dimensions.…”

“…20,21 The maintenance of volumetric shape and dimensions has only been realized in a small number of studies. [17][18][19][20][21] Here, we devised a 40-mm novel hybrid implant consisting of a cellular alginate layer with human ASCs encapsulating an acellular core of PEG-diacrylate (PEGDA) photopolymerized into breast shape. After in vivo implantation, vascularized adipose tissue regenerated in ASC-seeded alginate layer with expression of human-specific peroxisome proliferator-activated receptor-g (PPAR-g) mRNA and ratspecific PECAM, demonstrating a viable approach for further scale-up of adipose tissue grafts as a biomaterial tissue expander for reconstruction of lumpectomy/mastectomy defects.…”

The Feasibility of Platelet-Rich Fibrin Matrix Filler in a Nude Mouse Model

“…They are currently the main source of growth factors that promote wound healing. Numerous studies have shown that platelet-rich plasma (PRP) promoted early wound healing [7][8][9] and was effective at enhancing the treatment of diabetic ulcers [10]. PRP is a desirable autologous source to promote soft-tissue deposition in areas of depletion, and it is often used in oral, maxillofacial, and plastic surgery procedures.…”