Combining Suture-Reinforced High Resilent Aligned Nanofibrous Yarn/Membrane and Their Hierarchically Assembled Fascicle Mimicking Scaffolds with Biochemical and Physical Cues for Tendon Tissue Engineering

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Tendon is a connective tissue that helps joint movement and maintains its stability. The native tendon consists of bundles of aligned collagen fibrils and it also has a depot of growth factors. Due to their continuous exposure to high tensional force, they are commonly injured and don’t heal fast due to the hypocellular nature of the tendon. The surgical treatments such as tendon gaping and grafting are gold standard for tendon repair. However, these treatment options using tendon grafts have their own disadvantages. Hence researchers are focusing on tissue engineered construct that can provide the necessary mechanical support for tendon healing and also act as a substrate for cell attachment and proliferation. The broad and long term objective of this proposal is to develop a high strength and functional tendon scaffold from electrospun aligned fibers. Though tissue engineering has achieved many alternatives in tissue regeneration, defects related to tendon injury repair using artificial functional implants is still un-resolvable. We address this problem by developing high strength tendon scaffold endowed with simultaneous high functional recovery and fast regeneration capability in vivo.The objective of this study is to develop three innovative 3D scaffold for tendon tissue engineering using electrospun aligned nanofibers of polycaprolactone (PCL)/gelatin/heparin in three years. In the first design, we will first prepare nanofiber yarn by collecting aligned nanofibers with a biodegradable suture as the core in order to reinforce the mechanical strength of the fibrous yarn. The final scaffold will be constructed by braiding three suture-reinforced fibrous yarns to introduce additional degree of flexibility for in vivo experiments and strengthen the mechanical properties of individual yarns. The second scaffold will contain two aligned nanofiber layer embedded with biodegradable Ethicon PDS II* 4-0 suture to impart high strength for the tendon scaffold. The sandwiched fifrous membrane will be rolled into a cylindrical shaped scaffold with protruded suture to falitate in vivo tendon repair surgery. The third scaffold will be wrapping bundles of fibrous yarn developed in the first scaffold design within a single layer of the fibrous membrane in the second scaffold to mimic the tendon fascicle structure. The aligned morphology of the outer layer can simultaneously support the attachment of tendon primary fibroblast, which are arranged in a parallel manner, guide cell proliferation along the axial orientation of nanofibers. To study the effects of a biochemical cue (growth factor) for tendon tissue development, basic fibroblast growth factor (FGF2), a growth factor that has been shown to enhance proliferation and migration of tenocytes, will be conjugated to fiber sutface through bio-affinity toward heparin. In vitro dynamic culture studies will be carried out in a bioreactor to investigate whether a physical cue offered by mechanical tension stimulation during cell culture could promote cell proliferation, migration, synthesis of extracellular matrix and maturation of tenocyte. Finally, an extensor digitorum tendon defect model in rabbits will be used to test whether the cell/scaffold construct can be used for regeneration of tendon tissue.

Project IDs

Project ID:PC10907-0954
External Project ID:MOST109-2314-B182-013-MY3
StatusFinished
Effective start/end date01/08/2031/07/21

Keywords

  • Tendon
  • tissue engineering
  • scaffold
  • electrospinning
  • yarn
  • fibroblast growth factor
  • tenocyte
  • fascicle
  • dynamic cell culture

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