PMID- 35278687
OWN - NLM
STAT- MEDLINE
DCOM- 20220426
LR  - 20220516
IS  - 1878-7568 (Electronic)
IS  - 1742-7061 (Linking)
VI  - 143
DP  - 2022 Apr 15
TI  - Injectable laminin-biofunctionalized gellan gum hydrogels loaded with myoblasts 
      for skeletal muscle regeneration.
PG  - 282-294
LID - S1742-7061(22)00139-8 [pii]
LID - 10.1016/j.actbio.2022.03.008 [doi]
AB  - Moderate muscular injuries that exceed muscular tissue's auto-healing capacity 
      are still a topic of noteworthy concern. Tissue engineering appeared as a 
      promising therapeutic strategy capable of overcoming this unmet clinical need. To 
      attain such goal, herein we propose an in situ-crosslinking gellan gum (GG)-based 
      hydrogel tethered with a skeletal muscle-inspired laminin-derived peptide 
      RKRLQVQLSIRTC(Q) and encapsulated with skeletal muscle cells (SMCs). Pre-hydrogel 
      solutions presented decreasing shear viscosity with increasing shear rate and 
      shear stress, and required low forces for extrusion, validating their 
      injectability. The GGDVS hydrogel was functionalized with Q-peptide with 30% of 
      efficiency. C2C12 were able to adhere to the developed hydrogel, remained living 
      and spreading 7 days post-encapsulation. Q-peptide release studies indicated that 
      25% of the unbound peptide can be released from the hydrogels up to 7 days, 
      dependent on the hydrogel formulation. Treatment of a chemically-induced muscular 
      lesion in mice with an injection of C2C12-laden hydrogels improved myogenesis, 
      primarily promoted by the C2C12. In accordance, a high density of myoblasts 
      (alpha-SA(+) and MYH7(+)) were localized in tissues treated with the C2C12 (alone or 
      encapsulated in the hydrogel). alpha-SA protein levels were significantly increased 8 
      weeks post-treatment with C2C12-laden hydrogels and MHC protein levels were 
      increased in all experimental groups 4 weeks post-treatment, in relation to the 
      SHAM. Neovascularization and neoinnervation was also detected in the defects. 
      Altogether, this study indicates that C2C12-laden hydrogels hold great potential 
      for skeletal muscle regeneration. STATEMENT OF SIGNIFICANCE: We developed an 
      injectable gellan gum-based hydrogel for delivering C2C12 into localized 
      myopathic model. The gellan gum was biofunctinalized with laminin-derived peptide 
      to mimic the native muscular ECM. In addition, hydrogel was physically tuned to 
      mimic the mechanical properties of native tissue. To the best of our knowledge, 
      this formula was used for the first time under the context of skeletal muscle 
      tissue regeneration. The injectability of the developed hydrogel provided 
      non-invasive administration method, combined with a reliable microenvironment 
      that can host C2C12 with nominal inflammation, indicated by the survival and 
      adhesion of encapsulated cells post-injection. The treatment of skeletal muscle 
      defect with the cell-laden hydrogel approach significantly enhanced the 
      regeneration of localized muscular trauma.
CI  - Copyright (c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights 
      reserved.
FAU - Alheib, Omar
AU  - Alheib O
AD  - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables 
      and Biomimetics, Headquarters of the European Institute of Excellence on Tissue 
      Engineering and Regenerative Medicine, University of Minho, Avepark, Parque de 
      Ciencia e Tecnologia, Zona Industrial da Gandra, Barco, Guimaraes 4805-017, 
      Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimaraes 
      4710-057, Portugal.
FAU - da Silva, Lucilia P
AU  - da Silva LP
AD  - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables 
      and Biomimetics, Headquarters of the European Institute of Excellence on Tissue 
      Engineering and Regenerative Medicine, University of Minho, Avepark, Parque de 
      Ciencia e Tecnologia, Zona Industrial da Gandra, Barco, Guimaraes 4805-017, 
      Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimaraes 
      4710-057, Portugal. Electronic address: lucilia.silva@i3bs.uminho.pt.
FAU - da Silva Morais, Alain
AU  - da Silva Morais A
AD  - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables 
      and Biomimetics, Headquarters of the European Institute of Excellence on Tissue 
      Engineering and Regenerative Medicine, University of Minho, Avepark, Parque de 
      Ciencia e Tecnologia, Zona Industrial da Gandra, Barco, Guimaraes 4805-017, 
      Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimaraes 
      4710-057, Portugal.
FAU - Mesquita, Katia A
AU  - Mesquita KA
AD  - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables 
      and Biomimetics, Headquarters of the European Institute of Excellence on Tissue 
      Engineering and Regenerative Medicine, University of Minho, Avepark, Parque de 
      Ciencia e Tecnologia, Zona Industrial da Gandra, Barco, Guimaraes 4805-017, 
      Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimaraes 
      4710-057, Portugal.
FAU - Pirraco, Rogerio P
AU  - Pirraco RP
AD  - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables 
      and Biomimetics, Headquarters of the European Institute of Excellence on Tissue 
      Engineering and Regenerative Medicine, University of Minho, Avepark, Parque de 
      Ciencia e Tecnologia, Zona Industrial da Gandra, Barco, Guimaraes 4805-017, 
      Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimaraes 
      4710-057, Portugal.
FAU - Reis, Rui L
AU  - Reis RL
AD  - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables 
      and Biomimetics, Headquarters of the European Institute of Excellence on Tissue 
      Engineering and Regenerative Medicine, University of Minho, Avepark, Parque de 
      Ciencia e Tecnologia, Zona Industrial da Gandra, Barco, Guimaraes 4805-017, 
      Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimaraes 
      4710-057, Portugal.
FAU - Correlo, Vitor M
AU  - Correlo VM
AD  - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables 
      and Biomimetics, Headquarters of the European Institute of Excellence on Tissue 
      Engineering and Regenerative Medicine, University of Minho, Avepark, Parque de 
      Ciencia e Tecnologia, Zona Industrial da Gandra, Barco, Guimaraes 4805-017, 
      Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimaraes 
      4710-057, Portugal. Electronic address: vitorcorrelo@i3bs.uminho.pt.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220309
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
RN  - 0 (Hydrogels)
RN  - 0 (Laminin)
RN  - 0 (Peptides)
RN  - 0 (Polysaccharides, Bacterial)
RN  - 7593U09I4D (gellan gum)
SB  - IM
MH  - Animals
MH  - *Hydrogels/chemistry/pharmacology
MH  - *Laminin/pharmacology
MH  - Mice
MH  - Muscle, Skeletal
MH  - Myoblasts
MH  - Peptides
MH  - Polysaccharides, Bacterial/chemistry/pharmacology
MH  - Tissue Engineering/methods
OTO - NOTNLM
OT  - C2C12
OT  - Gellan gum
OT  - Hydrogel
OT  - Skeletal muscle tissue engineering
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/03/13 06:00
MHDA- 2022/04/27 06:00
CRDT- 2022/03/12 20:10
PHST- 2021/11/29 00:00 [received]
PHST- 2022/02/25 00:00 [revised]
PHST- 2022/03/04 00:00 [accepted]
PHST- 2022/03/13 06:00 [pubmed]
PHST- 2022/04/27 06:00 [medline]
PHST- 2022/03/12 20:10 [entrez]
AID - S1742-7061(22)00139-8 [pii]
AID - 10.1016/j.actbio.2022.03.008 [doi]
PST - ppublish
SO  - Acta Biomater. 2022 Apr 15;143:282-294. doi: 10.1016/j.actbio.2022.03.008. Epub 
      2022 Mar 9.