title: Winner of the Young Investigator Award of the Society for Biomaterials at the 10th World Biomaterials Congress, May 17-22, 2016, Montreal QC, Canada: Microribbon-based hydrogels accelerate stem cell-based bone regeneration in a mouse critical-size cranial defect model.
abstract: Stem cell-based therapies hold great promise for enhancing tissue regeneration. However, the majority of cells die shortly after transplantation, which greatly diminishes the efficacy of stem cell-based therapies. Poor cell engraftment and survival remain a major bottleneck to fully exploiting the power of stem cells for regenerative medicine. Biomaterials such as hydrogels can serve as artificial matrices to protect cells during delivery and guide desirable cell fates. However, conventional hydrogels often lack macroporosity, which restricts cell proliferation and delays matrix deposition. Here we report the use of injectable, macroporous microribbon (μRB) hydrogels as stem cell carriers for bone repair, which supports direct cell encapsulation into a macroporous scaffold with rapid spreading. When transplanted in a critical-sized, mouse cranial defect model, μRB-based hydrogels significantly enhanced the survival of transplanted adipose-derived stromal cells (ADSCs) (81%) and enabled up to three-fold cell proliferation after 7 days. In contrast, conventional hydrogels only led to 27% cell survival, which continued to decrease over time. MicroCT imaging showed μRBs enhanced and accelerated mineralized bone repair compared to hydrogels (61% vs. 34% by week 6), and stem cells were required for bone repair to occur. These results suggest that paracrine signaling of transplanted stem cells are responsible for the observed bone repair, and enhancing cell survival and proliferation using μRBs further promoted the paracrine-signaling effects of ADSCs for stimulating endogenous bone repair. We envision μRB-based scaffolds can be broadly useful as a novel scaffold for enhancing stem cell survival and regeneration of other tissue types. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1321-1331, 2016.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, 300 Pasteur Dr, Edward Building Room 114, Stanford, California 94305.
authors.forename: Li-Hsin
authors.initials: LH
authors.lastname: Han
authors.affiliation: Program of Stem Cell Biology and Regenerative Medicine, Stanford University, 300 Pasteur Dr, Edward Building Room 114, Stanford, California 94305.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Conrad
authors.affiliation: Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, 257 Campus Dr, Hagey Building Room GK106, Stanford, California 94305.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chung
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, 300 Pasteur Dr, Edward Building Room 114, Stanford, California 94305.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Deveza
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, 300 Pasteur Dr, Edward Building Room 114, Stanford, California 94305.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Dr, Grant Building Room H307A, Stanford, California 94305.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Dr, Grant Building Room H307A, Stanford, California 94305.
authors.forename: Manish J
authors.initials: MJ
authors.lastname: Butte
authors.affiliation: Division of Plastic and Reconstructive Surgery, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 257 Campus Dr, Hagey Building Room GK106, Stanford, California 94305.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.affiliation: Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, 257 Campus Dr, Hagey Building Room GK106, Stanford, California 94305.
authors.forename: Derrick
authors.initials: D
authors.lastname: Wan
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, 300 Pasteur Dr, Edward Building Room 114, Stanford, California 94305.|Department of Bioengineering, Stanford University, 300 Pasteur Dr, Edward Building Room 114, Stanford, California 94305.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001363:Awards and Prizes; D001672:Biocompatible Materials / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002170:Canada; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D020100:Hydrogels / Q000494:pharmacology*; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019899:Paracrine Communication / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry; D055114:X-Ray Microtomography
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels
keywords: bone; hydrogels; injectable; macroporous; stem cells