title: In Vivo Evaluation of Adipose-Derived Stromal Cells Delivered with a Nanofiber Scaffold for Tendon-to-Bone Repair.
abstract: Rotator cuff tears are common and cause a great deal of lost productivity, pain, and disability. Tears are typically repaired by suturing the tendon back to its bony attachment. Unfortunately, the structural (e.g., aligned collagen) and compositional (e.g., a gradient in mineral) elements that produce a robust attachment in the healthy tissue are not regenerated during healing, and the repair is prone to failure. Two features of the failed healing response are deposition of poorly aligned scar tissue and loss of bone at the repair site. Therefore, the objective of the current study was to improve tendon-to-bone healing by promoting aligned collagen deposition and increased bone formation using a biomimetic scaffold seeded with pluripotent cells. An aligned nanofibrous poly(lactic-co-glycolic acid) scaffold with a gradient in mineral content was seeded with adipose-derived stromal cells (ASCs) and implanted at the repair site of a rat rotator cuff model. In one group, cells were transduced with the osteogenic factor bone morphogenetic protein 2 (BMP2). The healing response was examined in four groups (suture only, acellular scaffold, cellular scaffold, and cellular BMP2 scaffold) using histologic, bone morphology, and biomechanical outcomes at 14, 28, and 56 days. Histologically, the healing interface was dominated by a fibrovascular scar response in all groups. The acellular scaffold group showed a delayed healing response compared to the other groups. When examining bone morphology parameters, bone loss was evident in the cellular BMP2 group compared to other groups at 28 days. When examining repair-site mechanical properties, strength and modulus were decreased in the cellular BMP2 groups compared to other groups at 28 and 56 days. These results indicated that tendon-to-bone healing in this animal model was dominated by scar formation, preventing any positive effects of the implanted biomimetic scaffold. Furthermore, cells transduced with the osteogenic factor BMP2 led to impaired healing, suggesting that this growth factor should not be used in the tendon-to-bone repair setting.
authors.affiliation: 1 Department of Orthopedic Surgery, Washington University in St. Louis , St. Louis, Missouri.|2 Department of Biomedical Engineering, Washington University in St. Louis , St. Louis, Missouri.
authors.forename: Justin
authors.initials: J
authors.lastname: Lipner
authors.affiliation: 1 Department of Orthopedic Surgery, Washington University in St. Louis , St. Louis, Missouri.
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.affiliation: 1 Department of Orthopedic Surgery, Washington University in St. Louis , St. Louis, Missouri.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Cavinatto
authors.affiliation: 3 School of Chemical and Biomolecular Engineering, Georgia Institute of Technology , Atlanta, Georgia .
authors.forename: Wenying
authors.initials: W
authors.lastname: Liu
authors.affiliation: 4 Department of Pathology, John Cochran VA Medical Center , St. Louis, Missouri.
authors.forename: Necat
authors.initials: N
authors.lastname: Havlioglu
authors.affiliation: 5 The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology , Atlanta, Georgia .
authors.forename: Younan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: 1 Department of Orthopedic Surgery, Washington University in St. Louis , St. Louis, Missouri.
authors.forename: Leesa M
authors.initials: LM
authors.lastname: Galatz
authors.affiliation: 6 Department of Orthopedic Surgery, Columbia University, New York, New York.
authors.forename: Stavros
authors.initials: S
authors.lastname: Thomopoulos
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001842:Bone and Bones / Q000473:pathology; D000069343:Bone-Implant Interface / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D004867:Equipment Design; D019544:Equipment Failure Analysis; D048091:Guided Tissue Regeneration / Q000295:instrumentation / Q000379:methods; D008297:Male; D008422:Materials Testing; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000295:instrumentation*; D013234:Stem Cells / Q000166:cytology*; D013708:Tendon Injuries / Q000473:pathology* / Q000628:therapy*; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D054457:Tissue Scaffolds; D016896:Treatment Outcome