title: Enhancement of rotator cuff tendon-bone healing with injectable periosteum progenitor cells-BMP-2 hydrogel in vivo.
abstract: OBJECTIVE
  The fixation and incorporation of ruptured rotator cuff tendon to bone is a major concern in rotator cuff repair surgery. Rotator cuff repair usually fails at the tendon-bone interface, especially in case of large or massive tears. To enhance tendon-bone healing, an injectable hydrogel made with periosteal progenitor cells(PPCs) and poly (ethylene glycol) diacrylate (PEGDA) tethered with bone morphogenic protein-2(BMP-2) was developed to encourage extracellular matrix synthesis for tendon-to-bone healing in rotator cuff repair.
  
  
  METHODS
  The infraspinatus tendon was cut from the greater tuberosity and repaired through a transosseous tunnel with the injectable progenitor cell-BMP-2 hydrogel applied between the tendon-bone interface. The injectable hydrogel was prepared from 10% poly (ethylene glycol) diacrylate (PEGDA) containing 0.05% of the photoinitiator. BMP-2 tethered with poly(ethylene glycol) (PEG) was blended to the hydrogel. Rabbit periosteal progenitor cells (PPCs) isolated from periosteum were mixed with hydrogel and injected on the tendon-bone interface. Ultraviolet radiation (365 nm) was applied for 60 s to photopolymerize the injection and solidify the hydrogel. The rabbits were killed at 4 and 8 weeks. The morphological characteristics of the healing tendon-to-bone interface were evaluated by histological and immunohistochemical methods. The biomechanical test was done to determine healing attachment strength.
  
  
  RESULTS
  At both the 4- and 8-week killing, histological analysis of the tendon-bone interface showed an increasing fibrocartilage and bone layer formed in the tendon-bone interface in PEGDA group. At 4 weeks, fibrocartilage-like tissue was observed in a focal area. At 8 weeks, further matrix deposition occurred with fibrocartilage formation in the tendon-bone junction, and bone formation appeared near host bone. Immunohistochemistry revealed the presence of aggrecan and type II collagen. Biomechanical testing revealed a higher maximum pull-out load at all time points with a statistically significant difference at 4 and 8 weeks postoperatively.
  
  
  CONCLUSIONS
  PEGDA hydrogel was approved as an adequate matrix for the encapsulation of cells and signal factor, and as an effective local delivery method to the tendon-bone interface through injection and photopolymerization. The PPCs-BMP2-hydrogel provides a powerful inductive ability between the tendon and the bone and enhances tendon-bone healing through the neoformation of fibrocartilage.
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital-Keelung, Chang Gung University, College of Medicine, Taoyuan, Taiwan. afachen@doctor.com
authors.forename: Chih-Hwa
authors.initials: CH
authors.lastname: Chen
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Chang
authors.forename: Kun-Chung
authors.initials: KC
authors.lastname: Wang
authors.forename: Chun-I
authors.initials: CI
authors.lastname: Su
authors.forename: Hsien-Tao
authors.initials: HT
authors.lastname: Liu
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Yu
authors.forename: Chak-Bor
authors.initials: CB
authors.lastname: Wong
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Wang
authors.forename: Shu Wen
authors.initials: SW
authors.lastname: Whu
authors.forename: Hsia-Wei
authors.initials: HW
authors.lastname: Liu
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001707:Biopsy, Needle; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects; D004195:Disease Models, Animal; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000627:therapeutic use; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D008297:Male; D010012:Osteogenesis / Q000502:physiology; D010521:Periosteum / Q000473:pathology / Q000601:surgery; D011817:Rabbits; D011897:Random Allocation; D017006:Rotator Cuff / Q000601:surgery*; D000070636:Rotator Cuff Injuries; D012785:Shoulder Joint / Q000473:pathology / Q000601:surgery*; D013234:Stem Cells; D013708:Tendon Injuries / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D013718:Tensile Strength; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D055396:Bone Morphogenetic Protein 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate