title: Effect of scaffold microarchitecture on osteogenic differentiation of human mesenchymal stem cells.
abstract: Design of macroporous synthetic grafts that can promote infiltration of cells, their differentiation, and synthesis of bone-specific extracellular matrix is a key determinant for in vivo bone tissue regeneration and repair. In this study, we investigated the effect of the microarchitecture of the scaffold on osteogenic differentiation of human mesenchymal stem cells (hMSCs). Poly(ethylene glycol) diacrylate-co-N-acryloyl 6-aminocaproic acid cryogels were fabricated to have either a pore network consisting of cellular, randomly oriented pores (termed 'spongy') or a pore network consisting of lamellar columns (termed 'columnar'), with both cryogel types showing a similar porosity. Both spongy and columnar cryogels supported comparable levels of cell viability and proliferation of hMSCs in vitro. However, spongy cryogels promoted osteogenic differentiation to a greater extent than their columnar counterparts, as evidenced by increased alkaline phosphatase activity and osteoblastic gene expression over 21 days post culture. Leveraging upon our previous work, we further evaluated the ability of these synthetic scaffolds in conjunction with mineralisation to promote ectopic bone formation upon subcutaneous implantation in nude rats. Mineralised spongy and columnar cryogels, both in the presence and absence of exogenous hMSCs, promoted ectopic bone formation in vivo. No such bone formation was observed in acellular cryogels devoid of mineralisation, with extensive host cell infiltration and vascularisation in columnar cryogels, and negligible infiltration into spongy cryogels. Our results thus present a novel method to tune the microarchitecture of porous polymeric scaffolds, in addition to suggesting their efficacy as synthetic bone grafts.
authors: Department of Bioengineering, University of California-San Diego, San Diego, CA, USA.
authors: Ameya
authors: A
authors: Phadke
authors: Department of Bioengineering, University of California-San Diego, San Diego, CA, USA.
authors: YongSung
authors: Y
authors: Hwang
authors: Biomaterials Research Centre, Korea Institute of Science and Technology, Seoul, Republic of Korea.
authors: Su Hee
authors: SH
authors: Kim
authors: Biomaterials Research Centre, Korea Institute of Science and Technology, Seoul, Republic of Korea.
authors: Soo Hyun
authors: SH
authors: Kim
authors: Department of Orthopaedic Surgery, University of California-San Diego, San Diego, CA, USA.|Graduate School of Life and Medical Sciences, Doshisha University, Kyoto, Japan.
authors: Tomonori
authors: T
authors: Yamaguchi
authors: Department of Orthopaedic Surgery, University of California-San Diego, San Diego, CA, USA.
authors: Koichi
authors: K
authors: Masuda
authors: Department of Bioengineering, University of California-San Diego, San Diego, CA, USA.
authors: Shyni
authors: S
authors: Varghese
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001861:Bone Regeneration; D018786:Bone Substitutes / Q000138:chemical synthesis; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D059985:Cryogels / Q000138:chemical synthesis*; D015870:Gene Expression; D006801:Humans; D020007:Implants, Experimental; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D011092:Polyethylene Glycols / Q000138:chemical synthesis; D058105:Polymerization; D016062:Porosity; D051381:Rats; D011923:Rats, Nude; D044968:Regenerative Medicine; D054457:Tissue Scaffolds
chemical_list: D018786:Bone Substitutes; D050659:Core Binding Factor Alpha 1 Subunit; D059985:Cryogels; C493709:RUNX2 protein, human; D015675:Osteocalcin; D053495:Osteopontin; D011092:Polyethylene Glycols; D000469:Alkaline Phosphatase