title: bFGF- and CaPP-Loaded Fibrin Clots Enhance the Bioactivity of the Tendon-Bone Interface to Augment Healing.
abstract: Tendon-to-bone healing is a complex and slow process, and the rate of poor healing remains high. In recent years, several new strategies have been developed that enhance tendon-to-bone healing by increasing the bioactivity. Fibrin clots have been widely used to improve tissue healing and tissue engineering,
  
  
  
  Modified fibrin clots can improve the bioactivity of the tendon-bone interface and histological appearance.
  
  
  
  Controlled laboratory study.
  
  
  
  A total of 27 male New Zealand White rabbits were used. Of these, 3 were used for cell isolation, and the remaining 24 rabbits were divided into 2 groups (12 per group) for an in vivo partial patellectomy study. The setting time, degradation time, and basic fibroblast growth factor (bFGF) and ceramide-activated protein phosphatase (CaPP) release kinetics of bFGF- and CaPP-loaded fibrin clots were modified appropriately for early tendon-to-bone healing. In an in vitro experiment, the bFGF- and CaPP-loaded fibrin clots were assessed for cell migration and proliferation by microscopy, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, and DAPI (4',6-diamidino-2-phenylindole) assay. Quantitative real-time reverse transcription polymerase chain reaction and a Western blot assay were performed to test for an induction effect of the bFGF- and CaPP-loaded fibrin clots. Finally, for the in vivo experiment, the rabbits were divided into 2 treatment groups: one with bFGF- and CaPP-loaded fibrin clots and one without bFGF- and CaPP-loaded fibrin clots after partial patellectomy in patella-patellar tendon sutured sites. A histological evaluation was performed at 2, 4, and 6 weeks after surgery.
  
  
  
  The sitting time and degradation time of the bFGF- and CaPP-loaded fibrin clots were set at 15 seconds and more than 2 weeks, respectively, and the porosity was minimized to achieve the highest levels of cell migration and growth. In the bFGF-CaPP group of the in vitro experiment, cell proliferation increased to a greater extent relative to the control group (P < .05); the mRNA expression of osteopontin, alkaline phosphatase, runt-related transcription factor 2, vascular endothelial growth factor, and collagen type I was upregulated (P < .05); and the relative protein expression of these factors was enhanced (P < .05). In vivo, hematoxylin and eosin staining showed that the tendon-to-bone connections were more mature and more arranged when treated with bFGF- and CaPP-loaded fibrin clots than when untreated, and the histological scores were higher.
  
  
  
  bFGF- and CaPP-loaded fibrin clots enhanced cell migration and proliferation and the expression of related genes and proteins, which increased the bioactivity of the tendon-bone interface and resulted in the histological improvement of tendon-to-bone healing.
  
  
  
  As fibrin clots have already been used in clinical practice, bFGF- and CaPP-loaded fibrin clots can be further used to augment healing in the early stages of tendon-to-bone healing.
authors.affiliation: Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Chenghao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China liqimm@yahoo.com hxlijian.china@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Senlin
authors.initials: S
authors.lastname: Deng
authors.affiliation: Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Institute of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Tingwu
authors.initials: T
authors.lastname: Qin
authors.affiliation: Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China liqimm@yahoo.com hxlijian.china@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000503:physiopathology*; D005337:Fibrin / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011817:Rabbits; D013708:Tendon Injuries / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D013710:Tendons / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D005337:Fibrin; D010749:Phosphoprotein Phosphatases
keywords: biological healing enhancement; fibrin clot; tendon-to-bone healing