PMID- 20379780 OWN - NLM STAT- MEDLINE DCOM- 20100913 LR - 20211020 IS - 1573-9686 (Electronic) IS - 0090-6964 (Print) IS - 0090-6964 (Linking) VI - 38 IP - 6 DP - 2010 Jun TI - Osteochondral interface tissue engineering using macroscopic gradients of bioactive signals. PG - 2167-82 LID - 10.1007/s10439-010-0028-0 [doi] AB - Continuous gradients exist at osteochondral interfaces, which may be engineered by applying spatially patterned gradients of biological cues. In the present study, a protein-loaded microsphere-based scaffold fabrication strategy was applied to achieve spatially and temporally controlled delivery of bioactive signals in three-dimensional (3D) tissue engineering scaffolds. Bone morphogenetic protein-2 and transforming growth factor-beta(1)-loaded poly(D,L-lactic-co-glycolic acid) microspheres were utilized with a gradient scaffold fabrication technology to produce microsphere-based scaffolds containing opposing gradients of these signals. Constructs were then seeded with human bone marrow stromal cells (hBMSCs) or human umbilical cord mesenchymal stromal cells (hUCMSCs), and osteochondral tissue regeneration was assessed in gradient scaffolds and compared to multiple control groups. Following a 6-week cell culture, the gradient scaffolds produced regionalized extracellular matrix, and outperformed the blank control scaffolds in cell number, glycosaminoglycan production, collagen content, alkaline phosphatase activity, and in some instances, gene expression of major osteogenic and chondrogenic markers. These results suggest that engineered signal gradients may be beneficial for osteochondral tissue engineering. FAU - Dormer, Nathan H AU - Dormer NH AD - Bioengineering Program, University of Kansas, Lawrence, KS 66045, USA. FAU - Singh, Milind AU - Singh M FAU - Wang, Limin AU - Wang L FAU - Berkland, Cory J AU - Berkland CJ FAU - Detamore, Michael S AU - Detamore MS LA - eng GR - R21 DE017673/DE/NIDCR NIH HHS/United States GR - T32 GM008359/GM/NIGMS NIH HHS/United States GR - T32-GM008359/GM/NIGMS NIH HHS/United States GR - 1 R21 DE017673-01/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100409 PL - United States TA - Ann Biomed Eng JT - Annals of biomedical engineering JID - 0361512 SB - IM MH - Cells, Cultured MH - Equipment Design MH - Humans MH - Male MH - Mesenchymal Stem Cells/*cytology/drug effects/*physiology MH - Osteogenesis/drug effects/*physiology MH - Signal Transduction/drug effects/physiology MH - Tissue Engineering/*instrumentation/methods MH - *Tissue Scaffolds MH - Young Adult PMC - PMC3773241 MID - NIHMS478423 EDAT- 2010/04/10 06:00 MHDA- 2010/09/14 06:00 PMCR- 2013/09/14 CRDT- 2010/04/10 06:00 PHST- 2009/12/30 00:00 [received] PHST- 2010/03/26 00:00 [accepted] PHST- 2010/04/10 06:00 [entrez] PHST- 2010/04/10 06:00 [pubmed] PHST- 2010/09/14 06:00 [medline] PHST- 2013/09/14 00:00 [pmc-release] AID - 10.1007/s10439-010-0028-0 [doi] PST - ppublish SO - Ann Biomed Eng. 2010 Jun;38(6):2167-82. doi: 10.1007/s10439-010-0028-0. Epub 2010 Apr 9.