Autologous adipose tissue grafting is a popular strategy for soft tissue reconstruction; yet its clinical outcomes are often suboptimal. Lack of metabolic and architectural support at recipient sites affects the capacity of cellularized autologous grafts to survive after transplantation. Allograft adipose matrices (AAMs) are composed of extracellular matrices of adipose tissue. They can provide critical biophysical cues and create a supportive microenvironment for autologous graft survival. Using murine models, we have optimized the in vivo use of an injectable AAM obtained from human cadaveric tissue and processed to remove lipid and cellular components. We hypothesized that the AAM could assist recipient site preparation before autologous adipose tissue grafting and—alone or combined with other treatments—improve surgical outcomes. The AAM scaffolds retained volume (measured as cross-sectional area at histology) over time and showed a higher local angiogenesis. Preconditioning of AAM recipient sites using intermittent external volume expansion further increased their vascularity and promoted adipogenesis. Low-density AAM combined with autologous adipose tissue grafts best assisted angiogenesis and tissue survival. These studies demonstrate that the AAM contributes to recipient site preparation before or in combination with autologous adipose tissue grafting by increasing vascularity and by creating an adipogenic microenvironment. This patient-ready scaffold could help improve outcomes in soft tissue reconstructive surgery.
Impact Statement
Trauma, disease, surgery, or congentital defects can cause soft tissue losses in patients, leading to disfigurement, functional impairment, and a low quality of life. In the lack of available effective methods to reconstruct these defects, acellular adipose matrices could provide a novel therapeutic solution to such challenge.
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References
1.
ColemanS.R.Structural fat grafting: more than a permanent filler. Plast Reconstr Surg, 118(3 Suppl.), 108S, 2006.
AghaR.A., FowlerA.J., HerlinC., GoodacreT.E.E., and OrgillD.P.Use of autologous fat grafting for breast reconstruction: a systematic review with meta-analysis of oncological outcomes. J Plast Reconstr Aesthet Surg, 68, 143, 2015.
4.
EtoH., KatoH., SugaH., et al.The fate of adipocytes after nonvascularized fat grafting: evidence of early death and replacement of adipocytes. Plast Reconstr Surg, 129, 1081–1092, 2012.
5.
GeisslerP.J., DavisK., RoostaeianJ., UngerJ., HuangJ., and RohrichR.J.Improving fat transfer viability: the role of aging, body mass index, and harvest site. Plast Reconstr Surg, 134, 227, 2014.
6.
SugaH., EtoH., AoiN., et al.Adipose tissue remodeling under ischemia: death of adipocytes and activation of stem/progenitor cells. Plast Reconstr Surg, 126, 1911, 2010.
7.
EtoH., SugaH., InoueK., et al.Adipose injury-associated factors mitigate hypoxia in ischemic tissues through activation of adipose-derived stem/progenitor/stromal cells and induction of angiogenesis. Am J Pathol, 178, 2322, 2011.
8.
SugaH., MatsumotoD., InoueK., et al.Numerical measurement of viable and nonviable adipocytes and other cellular components in aspirated fat tissue. Plast Reconstr Surg, 122, 103, 2008.
9.
HeitY.I., LancerottoL., MesteriI., et al.External volume expansion increases subcutaneous thickness, cell proliferation, and vascular remodeling in a murine model. Plast Reconstr Surg, 130, 541, 2012.
10.
KhouriR.K., RigottiG., KhouriR.K., et al.Tissue-engineered breast reconstruction with Brava-assisted fat grafting: a 7-year, 488-patient, multicenter experience. Plast Reconstr Surg, 135, 643, 2015.
11.
GiatsidisG., ChengL., FacchinF., et al.Moderate-intensity intermittent external volume expansion optimizes the soft tissue response in a murine model. Plast Reconstr Surg, 139, 882, 2017.
12.
WangL., JohnsonJ.A., ZhangQ., and BeahmE.K.Combining decellularized human adipose tissue extracellular matrix and adipose-derived stem cells for adipose tissue engineering. Acta Biomater, 9, 8921, 2013.
13.
FlynnL.E.The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells. Biomaterials, 31, 4715, 2010.
14.
FlynnL., PrestwichG.D., SempleJ.L., and WoodhouseK.A.Adipose tissue engineering with naturally derived scaffolds and adipose-derived stem cells. Biomaterials, 28, 3834, 2007.
15.
TurnerA.E., YuC., BiancoJ., WatkinsJ.F., and FlynnL.E.The performance of decellularized adipose tissue microcarriers as an inductive substrate for human adipose-derived stem cells. Biomaterials, 33, 4490, 2012.
16.
YuC., BiancoJ., BrownC., et al.Porous decellularized adipose tissue foams for soft tissue regeneration. Biomaterials, 34, 3290, 2013.
17.
HanT.T.Y., ToutounjiS., AmsdenB.G., and FlynnL.E.Adipose-derived stromal cells mediate in vivo adipogenesis, angiogenesis and inflammation in decellularized adipose tissue bioscaffolds. Biomaterials, 72, 125, 2015.
18.
HaddadS.M.H., OmidiE., FlynnL.E., and SamaniA.Comparative biomechanical study of using decellularized human adipose tissues for post-mastectomy and post-lumpectomy breast reconstruction. J Mech Behav Biomed Mater, 57, 235, 2016.
19.
CheungH.K., HanT.T.Y., MarecakD.M., WatkinsJ.F., AmsdenB.G., and FlynnL.E.Composite hydrogel scaffolds incorporating decellularized adipose tissue for soft tissue engineering with adipose-derived stem cells. Biomaterials, 35, 1914, 2014.
20.
ComptonC.C., ButlerC.E., YannasI.V., WarlandG., and OrgillD.P.Organized skin structure is regenerated in vivo from collagen-GAG matrices seeded with autologous keratinocytes. J Invest Dermatol, 110, 908, 1998.
21.
YannasI.V., LeeE., OrgillD.P., SkrabutE.M., and MurphyG.F.Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin. Proc Natl Acad Sci U S A, 86, 933, 1989.
22.
ClimovM., BayerL.R., MoscosoA.V., MatsumineH., and OrgillD.P.The role of dermal matrices in treating inflammatory and diabetic wounds. Plast Reconstr Surg, 138(3 Suppl.), 148S, 2016.
23.
JansenL.A., De CaignyP., GuayN.A., LineaweaverW.C., and ShokrollahiK.The evidence base for the acellular dermal matrix AlloDerm: a systematic review. Ann Plast Surg, 70, 587, 2013.
24.
EweidaA.M., and MareiM.K.Naturally occurring extracellular matrix scaffolds for dermal regeneration: do they really need cells?. Biomed Res Int, 2015, 839694, 2015.
25.
OmidiE., FuettererL., Reza MousaviS., ArmstrongR.C., FlynnL.E., and SamaniA.Characterization and assessment of hyperelastic and elastic properties of decellularized human adipose tissues. J Biomech, 47, 3657, 2014.
26.
GiatsidisG., Dalla VeneziaE., VeneziaE.D., De StefaniD., RizzutoR., and BassettoF.Breast tissue engineering: decellularized scaffolds derived from porcine mammary glands. Plast Reconstr Surg, 136(4 Suppl.), 35, 2015.
27.
YuC., KornmullerA., BrownC., HoareT., and FlynnL.E.Decellularized adipose tissue microcarriers as a dynamic culture platform for human adipose-derived stem/stromal cell expansion. . Biomaterials, 120, 66, 2017.
28.
BrownB.N., FreundJ.M., HanL., et al.Comparison of three methods for the derivation of a biologic scaffold composed of adipose tissue extracellular matrix. Tissue Eng Part C Methods, 17, 411, 2011.
29.
BanyardD.A., BoradV., AmezcuaE., WirthG.A., EvansG.R.D., and WidgerowA.D.Preparation, characterization, and clinical implications of human decellularized adipose tissue extracellular matrix (hDAM): a comprehensive review. Aesthet Surg J, 36, 349, 2016.
30.
RoehmK.D., HornbergerJ., and MadihallyS.V.In vitro characterization of acelluar porcine adipose tissue matrix for use as a tissue regenerative scaffold. J Biomed Mater Res A, 104, 3127, 2016.
31.
ChoiY.C., ChoiJ.S., KimB.S., KimJ.D., YoonH.I., and ChoY.W.Decellularized extracellular matrix derived from porcine adipose tissue as a xenogeneic biomaterial for tissue engineering. Tissue Eng Part C Methods, 18, 866, 2012.
32.
TanQ.W., ZhangY., LuoJ.C., et al.Hydrogel derived from decellularized porcine adipose tissue as a promising biomaterial for soft tissue augmentation. J Biomed Mater Res A, 105, 1756, 2017.
33.
LinC.-Y., LiuT.-Y., ChenM.-H., SunJ.-S., and ChenM.-H.An injectable extracellular matrix for the reconstruction of epidural fat and the prevention of epidural fibrosis. Biomed Mater, 11, 035010, 2016.
34.
ZelenC.M., OrgillD.P., SerenaT.E., et al.Human reticular acellular dermal matrix in the healing of chronic diabetic foot ulcerations that failed standard conservative treatment: a retrospective crossover study. Wounds, 29, 39, 2017.
35.
SbitanyH., and SerlettiJ.M.Acellular dermis-assisted prosthetic breast reconstruction: a systematic and critical review of efficacy and associated morbidity. Plast Reconstr Surg, 128, 1162, 2011.
36.
RENUVA® allograft adipose matrix instructions for use read before using donated human tissue description and indications for use. Available at: https://www.mtf.org/documents/PI_113_REV_5.pdf (accessed April19, 2018).
37.
ShahinT.B., VaishnavK.V., WatchmanM., et al.Tissue augmentation with allograft adipose matrix for the diabetic foot in remission. Plast Reconstr Surg Glob Open, 5, e1555, 2017.
38.
LancerottoL., ChinM.S., FreniereB., et al.Mechanisms of action of external volume expansion devices. Plast Reconstr Surg, 132, 569, 2013.
39.
Lujan-HernandezJ., LancerottoL., NabzdykC., et al.Induction of adipogenesis by external volume expansion. Plast Reconstr Surg, 137, 122, 2016.
40.
GiatsidisG., ChengL., HaddadA., et al.Noninvasive induction of angiogenesis in tissues by external suction: sequential optimization for use in reconstructive surgery. Angiogenesis, 21, 61, 2018.
41.
ThanikV.D., ChangC.C., LermanO.Z., et al.A murine model for studying diffusely injected human fat. Plast Reconstr Surg, 124, 74, 2009.
42.
LouisK.S., and SiegelA.C.Cell viability analysis using trypan blue: manual and automated methods. Methods Mol Biol, 740, 7, 2011.
43.
WeiS., OrgillD.P., and GiatsidisG.Delivery of external volume expansion (EVE) through micro-deformational interfaces safely induces angiogenesis in a murine model of intact diabetic skin with endothelial cell dysfunction (ECD). Plast Reconstr Surg. 2018, In press.
44.
KatoH., SugaH., EtoH., et al.Reversible adipose tissue enlargement induced by external tissue suspension: possible contribution of basic fibroblast growth factor in the preservation of enlarged tissue. Tissue Eng Part A, 16, 2029, 2010.
45.
KatoH., ArakiJ., DoiK., et al. Normobaric hyperoxygenation enhances initial survival, regeneration, and final retention in fat grafting. Plast Reconstr Surg, 134, 951, 2014.
46.
BrownC.F.C., YanJ., HanT.T.Y., MarecakD.M., AmsdenB.G., and FlynnL.E.Effect of decellularized adipose tissue particle size and cell density on adipose-derived stem cell proliferation and adipogenic differentiation in composite methacrylated chondroitin sulphate hydrogels. Biomed Mater, 10, 045010, 2015.
47.
KhouriR.K., KhouriR.-E.R., Lujan-HernandezJ.R., KhouriK.R., LancerottoL., and OrgillD.P.Diffusion and perfusion: the keys to fat grafting. Plast Reconstr Surg Glob Open 2, e220, 2014.
48.
KhouriR.K., RigottiG., CardosoE., KhouriR.K., and BiggsT.M.Megavolume autologous fat transfer: part II. Practice and techniques. Plast Reconstr Surg, 133, 1369, 2014.
49.
GirP., BrownS.A., OniG., KashefiN., MojallalA., and RohrichR.J.Fat grafting: evidence-based review on autologous fat harvesting, processing, reinjection, and storage. Plast Reconstr Surg, 130, 249, 2012.
50.
ColemanS.R., and KatzelE.B.Fat grafting for facial filling and regeneration. Clin Plast Surg, 42, 289, 2015.
51.
RaoA., and SaadehP.B.Defining fat necrosis in plastic surgery. Plast Reconstr Surg, 134, 1202, 2014.
52.
SzadeA., Grochot-PrzeczekA., FlorczykU., JozkowiczA., and DulakJ.Cellular and molecular mechanisms of inflammation-induced angiogenesis. IUBMB Life, 67, 145, 2015.
53.
KweeB.J., and MooneyD.J.Manipulating the intersection of angiogenesis and inflammation. Ann Biomed Eng, 43, 628, 2015.
54.
MorrisonW.A., MarreD., GrinsellD., BattyA., TrostN., and O'ConnorA.J.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.EBioMedicine, 6, 238, 2016.
55.
ChinM.S., Lujan-HernandezJ., BabchenkoO., et al.External volume expansion in irradiated tissue: effects on the recipient site. Plast Reconstr Surg, 137, 799e, 2016.
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