Review Article Human adipose-derived stem cells and three-dimensional scaffold constructs: A review of the biomaterials and models currently used for bone regeneration Andrea S. Zanetti, 1 Cristina Sabliov, 1 Jeffrey M. Gimble, 2 Daniel J. Hayes 1 1 Department of Biological and Agricultural Engineering, Louisiana State University and LSU AgCenter, Louisiana 2 Pennington Biomedical Research Center, Stem Cell Biology Lab, Louisiana State University, Louisiana Received 1 February 2012; revised 28 July 2012; accepted 7 August 2012 Published online 21 September 2012 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.32817 Abstract: In the past decade, substantial strides have been taken toward the use of human adipose-derived stromal/ stem cells (hASC) in the regeneration of bone. Since the dis- covery of the hASC osteogenic potential, many models have combined hASC with biodegradable scaffold materials. In general, rats and immunodeficient (nude) mice models for nonweight bearing bone formation have led the way to assess hASC osteogenic potential in vivo. The goal of this review is to present an overview of the recent literature describing hASC osteogenesis in conjuction with three- dimensional scaffolds for bone regeneration. V C 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 187–199, 2013. Key Words: animal model, bone, calcium phosphate(s), com- posite/hard tissue, osteogenesis How to cite this article: Zanetti AS, Sabliov C, Gimble JM, Hayes DJ 2013. Human adipose-derived stem cells and three- dimensional scaffold constructs: A review of the biomaterials and models currently used for bone regeneration. J Biomed Mater Res Part B 2013:101B:187–199. INTRODUCTION Since the discovery of the human adipose-derived mesen- chymal stem cells (hAMSC) osteogenesis, 1,2 research has substantially progressed toward the use of human adipose- derived stem cells (hASC) as a cell source for bone regener- ation. Although some applications would initially involve direct administration of stem cells into the target fracture site, current paradigms describing scaffolds loaded with stem cells are thought to be preferential in guiding bone regeneration by providing support for cell colonization, migration, growth, and differentiation. 3 During the preced- ing decade, several cell characterization studies have exten- sively described the differentiation potential and function of hACS both in vitro and in vivo along with the benefits of scaffold directed hASC osteogenesis (Table I). Perhaps, the most compelling evidence supporting the emerging clinical applications of hASC–scaffolds to promote fracture healing in humans was reported in 2004 after a combination of autogenous hASC and bone grafts were used to treat an extensive craniofacial injury in a 7-year-old girl. 4 In the literature, scaffold-based bone tissue engineering in combination with adult stem cells is well established, 32–37 however compiled information regarding scaffold use in combination with hASC is still lacking. Therefore, this review will present a historical background on hASC osteo- genesis; along with the findings of the current in vitro and in vivo hASC–scaffolds models as discussed with emphasis on biomaterial properties. Finally, a brief discussion on the potential impact of standardization of the current protocols for future hASC–scaffolds applications is also described. hASC OSTEOGENESIS: A RETROSPECTIVE ANALYSIS Isolation, characterization, and problems with nomenclature The term processed lipoaspirate (PLA) cells was first used to describe a subpopulation of progenitor cells isolated from human lipoaspirates in 2001. 2 Although the osteogenic poten- tial of PLA cells remained unknown in this report, abnormal adipose tissue mineralization was a well-known pathologic process in several diseases. 38 Moreover, the embryologic ori- gin of adipose tissue offered clues of the presence of a mesen- chymal stem cell (MSC) population in PLA cells. 1 Confirma- tion of the multilineage potential of these PLA cells was provided 1 year later by the same group. 39 To date, elective subcutaneous liposuction procedures remain the gold standard for human adipose tissue collection. 1,2,40 The Correspondence to: D. J. Hayes; e-mail: danielhayes@lsu.edu V C 2012 WILEY PERIODICALS, INC. 187