title: The use of ASCs engineered to express BMP2 or TGF-β3 within scaffold constructs to promote calvarial bone repair.
abstract: Calvarial bone healing is difficult and grafts comprising adipose-derived stem cells (ASCs) and PLGA (poly(lactic-co-glycolic acid)) scaffolds barely heal rabbit calvarial defects. Although calvarial bone forms via intramembranous ossification without cartilage templates, it was suggested that chondrocytes/cartilages promote calvarial healing, thus we hypothesized that inducing ASCs chondrogenesis and endochondral ossification involving cartilage formation can improve calvarial healing. To evaluate this hypothesis and selectively induce osteogenesis/chondrogenesis, rabbit ASCs were engineered to express the potent osteogenic (BMP2) or chondrogenic (TGF-β3) factor, seeded into either apatite-coated PLGA or gelatin sponge scaffolds, and allotransplanted into critical-size calvarial defects. Among the 4 ASCs/scaffold constructs, gelatin constructs elicited in vitro chondrogenesis, in vivo osteogenic metabolism and calvarial healing more effectively than apatite-coated PLGA, regardless of BMP2 or TGF-β3 expression. The BMP2-expressing ASCs/gelatin triggered better bone healing than TGF-β3-expressing ASCs/gelatin, filling ≈ 86% of the defect area and ≈ 61% of the volume at week 12. The healing proceeded via endochondral ossification, instead of intramembranous pathway, as evidenced by the formation of cartilage that underwent osteogenesis and hypertrophy. These data demonstrated ossification pathway switching and significantly augmented calvarial healing by the BMP2-expressing ASCs/gelatin constructs, and underscored the importance of growth factor/scaffold combinations on the healing efficacy and pathway.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Chang
authors.forename: Kuei-Chang
authors.initials: KC
authors.lastname: Li
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Lu
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Sung
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Yeh
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.forename: Shiu-Feng
authors.initials: SF
authors.lastname: Huang
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Hu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D060846:Cell Engineering; D002478:Cells, Cultured; D020219:Chondrogenesis; D005780:Gelatin / Q000737:chemistry; D015870:Gene Expression; D019344:Lactic Acid / Q000737:chemistry; D010012:Osteogenesis; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D012886:Skull / Q000293:injuries*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry*; D053782:Transforming Growth Factor beta3 / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing
chemical_list: D055396:Bone Morphogenetic Protein 2; D053782:Transforming Growth Factor beta3; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005780:Gelatin
keywords: BMP2; Calvarial bone healing; Endochondral ossification; Gelatin sponge; Intramembranous ossification; Tissue engineering