title: Nano-ceramic composite scaffolds for bioreactor-based bone engineering.
abstract: BACKGROUND
  Composites of biodegradable polymers and bioactive ceramics are candidates for tissue-engineered scaffolds that closely match the properties of bone. We previously developed a porous, three-dimensional poly (D,L-lactide-co-glycolide) (PLAGA)/nanohydroxyapatite (n-HA) scaffold as a potential bone tissue engineering matrix suitable for high-aspect ratio vessel (HARV) bioreactor applications. However, the physical and cellular properties of this scaffold are unknown. The present study aims to evaluate the effect of n-HA in modulating PLAGA scaffold properties and human mesenchymal stem cell (HMSC) responses in a HARV bioreactor.
  
  
  OBJECTIVE
  By comparing PLAGA/n-HA and PLAGA scaffolds, we asked whether incorporation of n-HA (1) accelerates scaffold degradation and compromises mechanical integrity; (2) promotes HMSC proliferation and differentiation; and (3) enhances HMSC mineralization when cultured in HARV bioreactors.
  
  
  METHODS
  PLAGA/n-HA scaffolds (total number = 48) were loaded into HARV bioreactors for 6 weeks and monitored for mass, molecular weight, mechanical, and morphological changes. HMSCs were seeded on PLAGA/n-HA scaffolds (total number = 38) and cultured in HARV bioreactors for 28 days. Cell migration, proliferation, osteogenic differentiation, and mineralization were characterized at four selected time points. The same amount of PLAGA scaffolds were used as controls.
  
  
  RESULTS
  The incorporation of n-HA did not alter the scaffold degradation pattern. PLAGA/n-HA scaffolds maintained their mechanical integrity throughout the 6 weeks in the dynamic culture environment. HMSCs seeded on PLAGA/n-HA scaffolds showed elevated proliferation, expression of osteogenic phenotypic markers, and mineral deposition as compared with cells seeded on PLAGA scaffolds. HMSCs migrated into the scaffold center with nearly uniform cell and extracellular matrix distribution in the scaffold interior.
  
  
  CONCLUSIONS
  The combination of PLAGA/n-HA scaffolds with HMSCs in HARV bioreactors may allow for the generation of engineered bone tissue.
  
  
  CONCLUSIONS
  In cases of large bone voids (such as bone cancer), tissue-engineered constructs may provide alternatives to traditional bone grafts by culturing patients' own MSCs with PLAGA/n-HA scaffolds in a HARV culture system.
authors: Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06003, USA.
authors: Qing
authors: Q
authors: Lv
authors: Meng
authors: M
authors: Deng
authors: Bret D
authors: BD
authors: Ulery
authors: Lakshmi S
authors: LS
authors: Nair
authors: Cato T
authors: CT
authors: Laurencin
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019149:Bioreactors; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002516:Ceramics / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D053761:Nanocomposites; D036103:Nanotechnology; D010012:Osteogenesis; D010641:Phenotype; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties; D013997:Time Factors; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D015415:Biomarkers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017886:Durapatite