An immunologically active, adipose-derived extracellular matrix biomaterial for soft tissue reconstruction: concept to clinical trial

AbstractSoft tissue reconstruction remains an intractable clinical challenge as current surgical options and synthetic implants may produce inadequate outcomes. Soft tissue deficits may be surgically reconstructed using autologous adipose tissue, but these procedures can lead to donor site morbidity, require multiple procedures, and have highly variable outcomes. To address this clinical need, we developed an “off-the-shelf” adipose extracellular matrix (ECM) biomaterial from allograft human tissue (Acellular Adipose Tissue, AAT). We applied physical and chemical processing methods to remove lipids and create an injectable matrix that mimicked the properties of lipoaspirate. Biological activity was assessed using cell migration and adipogenesis assays. Characterization of regenerative immune properties in a murine muscle injury model revealed that allograft and xenograft AAT induced pro-regenerative CD4+ T cells and macrophages with xenograft AAT additionally attracting eosinophils secreting interleukin 4 (Il4). In immunocompromised mice, AAT injections retained similar volumes as human fat grafts but lacked cysts and calcifications seen in the fat grafts. The combination of AAT with human adipose-derived stem cells (ASCs) resulted in lower implant volumes. However, tissue remodeling and adipogenesis increased significantly in combination with ASCs. Larger injected volumes of porcine-derived AAT demonstrated biocompatibility and greater retention when applied allogeneicly in Yorkshire cross pigs. AAT was implanted in healthy volunteers in abdominal tissue that was later removed by elective procedures. AAT implants were well tolerated in all human subjects. Implants removed between 1 and 18 weeks demonstrated increasing cellular infiltration and immune populations, suggesting continued tissue remodeling and the potential for long-term tissue replacement.

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An immunologically active, adipose-derived extracellular matrix biomaterial for soft tissue reconstruction: concept to clinical trial

10.1101/2020.10.08.20206672 ◽

2020 ◽

Author(s):

Amy E. Anderson ◽

Iwen Wu ◽

Alexis J. Parrillo ◽

David R. Maestas ◽

Ian Graham ◽

...

Keyword(s):

Adipose Tissue ◽

Soft Tissue ◽

Human Subjects ◽

Donor Site ◽

Tissue Remodeling ◽

Fat Grafting ◽

Interleukin 4 ◽

Fat Graft ◽

Soft Tissue Reconstruction ◽

Tissue Reconstruction

ABSTRACTSoft tissue reconstruction remains an intractable clinical challenge as current surgical options and synthetic implants may produce inadequate outcomes. Soft tissue deficits may be surgically reconstructed using autologous adipose tissue, but these procedures can lead to donor site morbidity, require multiple trips to the operating room, and have highly variable outcomes. To address the clinical need for soft tissue reconstruction, we developed an “off-the-shelf” adipose matrix from allograft human adipose tissue (acellular adipose tissue, AAT). We applied physical and chemical processing methods to remove lipids and create an injectable matrix that mimicked the properties of fat grafting materials. Biological activity was assessed using cell migration and stem cell adipogenesis assays. Characterization of the regenerative immunology properties in a murine muscle injury model revealed allograft and xenograft AAT induced pro-regenerative CD4+ T cells and macrophages with xenograft AAT attracting additional eosinophils secreting interleukin 4 (Il4). In immunocompromised mice, AAT injections retained similar tissue volumes as human fat grafts but did not have the cysts and calcifications that formed in the human fat graft implants. Combination of AAT with human adipose-derived stem cells (ASCs) resulted in lower implant volumes. However, tissue remodeling and new adipose development increased significantly with the addition of cells. Larger injected volumes of porcine-derived AAT demonstrated biocompatibility and greater volume retention when applied allogeneicly in Yorkshire cross pigs. Under a biologic IND application, AAT was implanted in healthy volunteers in abdominal tissue that was later removed (panniculectomy or abdominoplasty). The AAT implants were well tolerated and biocompatible in all eight human subjects. Analysis of implants removed between 1 and 18 weeks demonstrated increasing cellular infiltration and immune populations, suggesting continued tissue remodeling and the potential for long term tissue replacement.SUMMARYAn adipose-derived injectable biomaterial provides volume correction for soft tissue defects while promoting pro-healing immune responses.

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Tissue Engineering of Vascularized Adipose Tissue for Soft Tissue Reconstruction

Stem Cells in Aesthetic Procedures ◽

10.1007/978-3-642-45207-9_3 ◽

2014 ◽

pp. 23-40

Author(s):

Silvan M. Klein ◽

Jody Vykoukal ◽

Lukas Prantl ◽

Juergen H. Dolderer

Keyword(s):

Tissue Engineering ◽

Adipose Tissue ◽

Soft Tissue ◽

Soft Tissue Reconstruction ◽

Tissue Reconstruction

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Submental Flap for Soft Tissue Reconstruction following Radical Parotidectomy

Otolaryngology ◽

10.1177/0194599819827822 ◽

2019 ◽

Vol 160 (6) ◽

pp. 1130-1132 ◽

Cited By ~ 2

Author(s):

Rodrigo Bayon ◽

Andrew B. Davis

Keyword(s):

Soft Tissue ◽

Medical Center ◽

Donor Site ◽

Case Series ◽

Island Flap ◽

Hospital Length Of Stay ◽

Soft Tissue Reconstruction ◽

Submental Flap ◽

Tissue Reconstruction ◽

Submental Island Flap

This study analyzed our institution’s experience with a buried submental flap for soft tissue reconstruction following radical parotidectomy. A retrospective chart review was conducted of patients who had parotid malignancies requiring radical parotidectomy, who also underwent a buried submental flap reconstruction. Analysis included patient demographics and clinical, surgical, and outcome data. Three patients met criteria for this study who underwent a buried submental flap at a tertiary medical center between 2012 and 2016. All patients had oncologic surgery and reconstruction using a deepithelialized submental island flap, which was used to fill the radical parotidectomy surgical defect with no complications and good aesthetic results. Each patient received appropriate adjuvant therapy. This case series shows that the buried submental island flap is a versatile flap that is adequate bulk after radical parotidectomy. It also has no impact on hospital length of stay and provides excellent cosmetic outcomes with minimal donor site morbidity.

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A Homodigital Reverse Pedicle Island Flap in Soft Tissue Reconstruction of the Finger and the Thumb

Journal of Hand Surgery (European Volume) ◽

10.1016/0266-7681(94)90149-x ◽

1994 ◽

Vol 19 (2) ◽

pp. 135-141 ◽

Cited By ~ 35

Author(s):

N. S. NIRANJAN ◽

J. R. ARMSTRONG

Keyword(s):

Soft Tissue ◽

Donor Site ◽

Donor Site Morbidity ◽

Single Stage ◽

Island Flap ◽

Tissue Loss ◽

Soft Tissue Reconstruction ◽

Tissue Reconstruction

A single stage homodigital reverse pedicle island flap is described for the repair of volar or dorsal tissue loss on the finger or thumb. Donor site morbidity is minimal, and the length of the digit is preserved. Satisfactory function results in 25 patients are presented.

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Minimally invasive soft tissue reconstruction with free peroneal artery perforator flap

Internal Medicine Review ◽

10.18103/imr.v2i8.173 ◽

2016 ◽

Vol 2 (8) ◽

Author(s):

Kenji Kawamura ◽

Hiroshi Yajima ◽

Shohei Omokawa ◽

Takamasa Shimizu ◽

Naoki Maegawa ◽

...

Keyword(s):

Soft Tissue ◽

Minimally Invasive ◽

Donor Site ◽

Perforator Flap ◽

Peroneal Artery ◽

Soft Tissue Reconstruction ◽

Perforator Flaps ◽

Major Vessel ◽

Tissue Reconstruction ◽

Artery Perforator

The development of a concept of perforator flap has dramatically changed the soft tissue reconstructive surgery. The surgery with perforator flaps enables to minimize donor-site morbidity by preserving important tissues including the muscle and the major vessel. The peroneal artery perforator flap is one of perforator flaps that can be harvested from the lower leg. The peroneal artery perforator flap has been widely used as a local flap for soft tissue reconstruction in the lower extremity; however, the free peroneal artery perforator flap transfer has been little reported. Utilities of the free peroneal artery perforator flap for soft tissue reconstruction of the extremities are reported, and minimally invasive flap surgery with perforator flaps is reviewed.

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EXTRACELLULAR MATRIX AS A BIOACTIVE MATERIAL FOR SOFT TISSUE RECONSTRUCTION

ANZ Journal of Surgery ◽

10.1111/j.1445-2197.2006.03970.x ◽

2006 ◽

Vol 76 (12) ◽

pp. 1047-1047 ◽

Cited By ~ 2

Author(s):

W. A. Morrison ◽

A. J. Hussey

Keyword(s):

Extracellular Matrix ◽

Soft Tissue ◽

Soft Tissue Reconstruction ◽

Bioactive Material ◽

Tissue Reconstruction

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Soft Tissue Reconstruction

Standards for the Management of Open Fractures ◽

10.1093/med/9780198849360.003.0008 ◽

2020 ◽

pp. 63-74

Keyword(s):

Soft Tissue ◽

Lower Limb ◽

Donor Site ◽

Free Flaps ◽

Donor Site Morbidity ◽

Open Fractures ◽

Soft Tissue Coverage ◽

Soft Tissue Reconstruction ◽

Tissue Reconstruction ◽

Wound Excision

Soft tissue coverage of open fractures with well-vascularised tissues should be performed within 72 hours of injury or at the same time as internal fixation. It may be in the form of local or free flaps, and may comprise muscle, fasciocutaneous tissues, or both. Flap selection depends on multiple factors, including the size and location of the defect following wound excision, availability of flaps, and donor site morbidity. Local flaps are usually used to cover defects with a limited zone of injury. Anastomoses for free flaps should be performed outside the zone of injury. Experimental data suggest that coverage with muscle leads to improved healing of fractures. However, there is currently little clinical evidence to support the use of one form of soft tissue cover over another for open fractures of the lower limb. The plastic surgeon must always consider the donor site morbidity of the flap(s) chosen.

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