Due to the limitations in autogenous nerve grafting or Schwann cell transplantation, large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit. Cell based therapies provide a novel treatment for peripheral nerve injuries. In this study, we first experimented an optimal scaffold material synthesis protocol, from where we selected the 10% GFD formula (10% GelMA hydrogel, recombinant human basic fibroblast growth factor and dental pulp stem cells (DPSCs)) to fill a cellulose/soy protein isolate composite membrane (CSM) tube to construct a third generation of nerve regeneration conduit, CSM-GFD. Then this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat model. After 12 week post implant surgery, at histologic level, we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve fibers. At physical level, CSM-GFD achieved functional recovery assessed by a sciatic functional index study. In both levels, CSM-GFD performed like what gold standard, the nerve autograft, could do. Further, we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in CSM-GFD. In conclusion, we claimed that this third-generation nerve regeneration conduit, CSM-GFD, could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.
基金:
National Natural Science Funding of China [81701032, 81871503]; Wenzhou Science and Technology Association Project; Wenzhou Major Scientific and Technological Innovation Key Medical and Health Project [ZY2019010]; Wenzhou Medical University [QTJ16026]; Wenzhou Science and Technology Association Project, Wenzhou Basic Research Project [Y20180131]; Zhejiang Province Program of the Medical and Health Science and Technology [2018KY537]; Zhejiang Natural Science Foundation [LGF18C100002]; Zhejiang Xinmiao Talents Program [2018R413186]
第一作者单位:[1]Wenzhou Med Univ, Sch & Hosp Stomatol, Wenzhou, Zhejiang, Peoples R China
通讯作者:
通讯机构:[1]Wenzhou Med Univ, Sch & Hosp Stomatol, Wenzhou, Zhejiang, Peoples R China[2]Wuhan Univ Sci & Technol, Tianyou Hosp, Wuhan 430064, Peoples R China[3]Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA 02114 USA[4]Harvard Sch Dent Med, Boston, MA 02114 USA[8]Huazhong Univ Sci & Technol,Affiliated Tongji Hosp,Tongji Med Coll,Dept Biliary & Pancreat Surg,Canc Res Ctr,Wuhan 430030,Peoples R China[9]Wuhan Univ, Ctr Regenerat Med, Renmin Hosp, Wuhan 430060, Peoples R China
推荐引用方式(GB/T 7714):
Luo Lihua,He Yan,Jin Ling,et al.Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries[J].BIOACTIVE MATERIALS.2021,6(3):638-654.doi:10.1016/j.bioactmat.2020.08.028.
APA:
Luo, Lihua,He, Yan,Jin, Ling,Zhang, Yanni,Guastaldi, Fernando P....&Ye, Qingsong.(2021).Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries.BIOACTIVE MATERIALS,6,(3)
MLA:
Luo, Lihua,et al."Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries".BIOACTIVE MATERIALS 6..3(2021):638-654