title: Uncultured adipose-derived regenerative cells (ADRCs) seeded in collagen scaffold improves dermal regeneration, enhancing early vascularization and structural organization following thermal burns.
abstract: OBJECTIVE
  Advances in tissue engineering have yielded a range of both natural and synthetic skin substitutes for burn wound healing application. Long-term viability of tissue-engineered skin substitutes requires the formation and maturation of neo-vessels to optimize survival and biointegration after implantation. A number of studies have demonstrated the capacity of Adipose Derived Regenerative Cells (ADRCs) to promote angiogenesis and modulate inflammation. On this basis, it was hypothesized that adding ADRCs to a collagen-based matrix (CBM) (i.e. Integra) would enhance formation and maturation of well-organized wound tissue in the setting of acute thermal burns. The purpose of this study was to evaluate whether seeding uncultured ADRCs onto CBM would improve matrix properties and enhance healing of the grafted wound.
  
  
  METHODS
  Full thickness thermal burns were created on the backs of 8 Gottingen mini-swine. Two days post-injury wounds underwent fascial excision and animals were randomized to receive either Integra seeded with either uncultured ADRCs or control vehicle. Wound healing assessment was performed by digital wound imaging, histopathological and immunohistochemical analyses.
  
  
  RESULTS
  In vitro analysis demonstrated that freshly isolated ADRCs adhered and propagated on the CBM. Histological scoring revealed accelerated maturation of wound bed tissue in wounds receiving ADRCs-loaded CBM compared to vehicle-loaded CBM. This was associated with a significant increase in depth of the wound bed tissue and collagen deposition (p<0.05). Blood vessel density in the wound bed was 50% to 69.6% greater in wounds receiving ADRCs-loaded CBM compared to vehicle-loaded CBM (p=0.05) at day 14 and 21. In addition, ADRCs delivered with CBM showed increased blood vessel lumen area and blood vessel maturation at day 21(p=0.05). Interestingly, vascularity and overall cellularity within the CBM were 50% and 45% greater in animals receiving ADRC loaded scaffolds compared to CBM alone (p<0.05).
  
  
  CONCLUSIONS
  These data demonstrate that seeding uncultured ADRCs onto CBM dermal substitute enhances wound angiogenesis, blood vessel maturation and matrix remodeling.
authors.affiliation: Cytori Therapeutics Inc, San Diego, CA, USA. Electronic address: pfoubert@cytori.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Foubert
authors.affiliation: Cytori Therapeutics Inc, San Diego, CA, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Barillas
authors.affiliation: Cytori Therapeutics Inc, San Diego, CA, USA.
authors.forename: Andreina D
authors.initials: AD
authors.lastname: Gonzalez
authors.affiliation: Cytori Therapeutics Inc, San Diego, CA, USA.
authors.forename: Zeni
authors.initials: Z
authors.lastname: Alfonso
authors.affiliation: Cytori Therapeutics Inc, San Diego, CA, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Comparative Biosciences Inc., Sunnyvale, CA, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Hakim
authors.affiliation: Comparative Biosciences Inc., Sunnyvale, CA, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Meschter
authors.affiliation: UCSD Medical Center, University of California, San Diego, CA, USA.
authors.forename: Mayer
authors.initials: M
authors.lastname: Tenenhaus
authors.affiliation: Cytori Therapeutics Inc, San Diego, CA, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Fraser
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002056:Burns / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D003094:Collagen; D004195:Disease Models, Animal; D012867:Skin / Q000098:blood supply*; D016038:Skin Transplantation; D017768:Skin, Artificial; D033581:Stem Cell Transplantation / Q000379:methods*; D013552:Swine; D013556:Swine, Miniature; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014945:Wound Healing
chemical_list: D003094:Collagen
keywords: Adipose-derived regenerative cells; Angiogenesis; Integra(®); Thermal burn