PMID- 36246376
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221019
IS  - 2296-4185 (Print)
IS  - 2296-4185 (Electronic)
IS  - 2296-4185 (Linking)
VI  - 10
DP  - 2022
TI  - Hypoxia-pretreated mesenchymal stem cell-derived exosomes-loaded low-temperature 
      extrusion 3D-printed implants for neural regeneration after traumatic brain 
      injury in canines.
PG  - 1025138
LID - 10.3389/fbioe.2022.1025138 [doi]
LID - 1025138
AB  - Regenerating brain defects after traumatic brain injury (TBI) still remains a 
      significant difficulty, which has motivated interest in 3D printing to design 
      superior replacements for brain implantation. Collagen has been applied to 
      deliver cells or certain neurotrophic factors for neuroregeneration. However, its 
      fast degradation rate and poor mechanical strength prevent it from being an 
      excellent implant material after TBI. In the present study, we prepared 
      3D-printed collagen/silk fibroin/hypoxia-pretreated human umbilical cord 
      mesenchymal stem cells (HUCMSCs)-derived exosomes scaffolds (3D-CS-HMExos), which 
      possessed favorable physical properties suitable biocompatibility and 
      biodegradability and were attractive candidates for TBI treatment. Furthermore, 
      inspired by exosomal alterations resulting from cells in different external 
      microenvironments, exosomes were engineered through hypoxia stimulation of 
      mesenchymal stem cells and were proposed as an alternative therapy for promoting 
      neuroregeneration after TBI. We designed hypoxia-preconditioned (Hypo) exosomes 
      derived from HUCMSCs (Hypo-MExos) and proposed them as a selective therapy to 
      promote neuroregeneration after TBI. For the current study, 3D-CS-HMExos were 
      prepared for implantation into the injured brains of beagle dogs. The addition of 
      hypoxia-induced exosomes further exhibited better biocompatibility and 
      neuroregeneration ability. Our results revealed that 3D-CS-HMExos could 
      significantly promote neuroregeneration and angiogenesis due to the doping of 
      hypoxia-induced exosomes. In addition, the 3D-CS-HMExos further inhibited nerve 
      cell apoptosis and proinflammatory factor (TNF-alpha and IL-6) expression and 
      promoted the expression of an anti-inflammatory factor (IL-10), ultimately 
      enhancing the motor functional recovery of TBI. We proposed that the 3D-CS-loaded 
      encapsulated hypoxia-induced exosomes allowed an adaptable environment for 
      neuroregeneration, inhibition of inflammatory factors and promotion of motor 
      function recovery in TBI beagle dogs. These beneficial effects implied that 
      3D-CS-HMExos implants could serve as a favorable strategy for defect cavity 
      repair after TBI.
CI  - Copyright (c) 2022 Liu, Wang, Wang, Zhong, Wang, Feng, Wei and Zhou.
FAU - Liu, Xiaoyin
AU  - Liu X
AD  - Department of Neurosurgery, West China Hospital, West China Medical School, 
      Sichuan University, Chengdu, Sichuan, China.
AD  - Tianjin Key Laboratory of Neurotrauma Repair, Institute of Neurotrauma Repair, 
      Characteristic Medical Center of People's Armed Police Forces, Tianjin, China.
FAU - Wang, Jingjing
AU  - Wang J
AD  - Tianjin Key Laboratory of Neurotrauma Repair, Institute of Neurotrauma Repair, 
      Characteristic Medical Center of People's Armed Police Forces, Tianjin, China.
FAU - Wang, Peng
AU  - Wang P
AD  - Department of Health Management, Tianjin Hospital, Tianjin, China.
FAU - Zhong, Lin
AU  - Zhong L
AD  - The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 
      China.
FAU - Wang, Shan
AU  - Wang S
AD  - Department of Neurosurgery, West China Hospital, West China Medical School, 
      Sichuan University, Chengdu, Sichuan, China.
FAU - Feng, Qingbo
AU  - Feng Q
AD  - Department of Liver Surgery and Liver Implantation, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Wei, Xin
AU  - Wei X
AD  - Department of Urology, Institute of Urology, West China Hospital, West China 
      Medical School, Sichuan University, Chengdu, Sichuan, China.
FAU - Zhou, Liangxue
AU  - Zhou L
AD  - Department of Neurosurgery, West China Hospital, West China Medical School, 
      Sichuan University, Chengdu, Sichuan, China.
LA  - eng
PT  - Journal Article
DEP - 20220930
PL  - Switzerland
TA  - Front Bioeng Biotechnol
JT  - Frontiers in bioengineering and biotechnology
JID - 101632513
PMC - PMC9562040
OTO - NOTNLM
OT  - 3D printing
OT  - collagen
OT  - exosomes
OT  - hypoxia
OT  - silk fibroin
OT  - traumatic brain injury
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/10/18 06:00
MHDA- 2022/10/18 06:01
PMCR- 2022/01/01
CRDT- 2022/10/17 04:30
PHST- 2022/08/22 00:00 [received]
PHST- 2022/09/13 00:00 [accepted]
PHST- 2022/10/17 04:30 [entrez]
PHST- 2022/10/18 06:00 [pubmed]
PHST- 2022/10/18 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 1025138 [pii]
AID - 10.3389/fbioe.2022.1025138 [doi]
PST - epublish
SO  - Front Bioeng Biotechnol. 2022 Sep 30;10:1025138. doi: 10.3389/fbioe.2022.1025138. 
      eCollection 2022.