PMID- 35356816
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220401
IS  - 2452-199X (Electronic)
IS  - 2452-199X (Linking)
VI  - 15
DP  - 2022 Sep
TI  - Alkaline activation of endogenous latent TGFbeta1 by an injectable hydrogel directs 
      cell homing for in situ complex tissue regeneration.
PG  - 316-329
LID - 10.1016/j.bioactmat.2021.12.015 [doi]
AB  - Utilization of the body's regenerative potential for tissue repair is known as in 
      situ tissue regeneration. However, the use of exogenous growth factors requires 
      delicate control of the dose and delivery strategies and may be accompanied by 
      safety, efficacy and cost concerns. In this study, we developed, for the first 
      time, a biomaterial-based strategy to activate endogenous transforming growth 
      factor beta 1 (TGFbeta1) under alkaline conditions for effective in situ tissue 
      regeneration. We demonstrated that alkaline-activated TGFbeta1 from blood serum, 
      bone marrow fluids and soaking solutions of meniscus and tooth dentin was capable 
      of increasing cell recruitment and early differentiation, implying its broad 
      practicability. Furthermore, we engineered an injectable hydrogel (MS-Gel) 
      consisting of gelatin microspheres for loading strong alkaline substances and a 
      modified gelatin matrix for hydrogel click crosslinking. In vitro models showed 
      that alkaline MS-Gel controllably and sustainably activated endogenous TGFbeta1 from 
      tooth dentin for robust bone marrow stem cell migration. More importantly, 
      infusion of in vivo porcine prepared root canals with alkaline MS-Gel promoted 
      significant pulp-dentin regeneration with neurovascular stroma and mineralized 
      tissue by endogenous proliferative cells. Therefore, this work offers a new 
      bench-to-beside translation strategy using biomaterial-activated endogenous 
      biomolecules to achieve in situ tissue regeneration without the need for cell or 
      protein delivery.
CI  - (c) 2021 The Authors.
FAU - Wang, Sainan
AU  - Wang S
AD  - Department of Cariology and Endodontology, Peking University School and Hospital 
      of Stomatology, Beijing, 100081, China.
AD  - Center for Craniofacial Regeneration, Columbia University, New York, NY, 10032, 
      USA.
FAU - Niu, Yuting
AU  - Niu Y
AD  - Department of Prosthodontics, Peking University School and Hospital of 
      Stomatology, Beijing, 100081, China.
AD  - Center for Craniofacial Regeneration, Columbia University, New York, NY, 10032, 
      USA.
FAU - Jia, Peipei
AU  - Jia P
AD  - Department of Cariology and Endodontology, Peking University School and Hospital 
      of Stomatology, Beijing, 100081, China.
FAU - Liao, Zheting
AU  - Liao Z
AD  - Center for Craniofacial Regeneration, Columbia University, New York, NY, 10032, 
      USA.
FAU - Guo, Weimin
AU  - Guo W
AD  - Center for Craniofacial Regeneration, Columbia University, New York, NY, 10032, 
      USA.
FAU - Chaves, Rodrigo Cotrim
AU  - Chaves RC
AD  - Department of Biomedical Engineering, Columbia University, New York, NY, 10027, 
      USA.
FAU - Tran-Ba, Khanh-Hoa
AU  - Tran-Ba KH
AD  - Department of Chemistry, Columbia University, New York, NY, 10027, USA.
FAU - He, Ling
AU  - He L
AD  - Center for Craniofacial Regeneration, Columbia University, New York, NY, 10032, 
      USA.
FAU - Bai, Hanying
AU  - Bai H
AD  - Center for Craniofacial Regeneration, Columbia University, New York, NY, 10032, 
      USA.
FAU - Sia, Sam
AU  - Sia S
AD  - Department of Biomedical Engineering, Columbia University, New York, NY, 10027, 
      USA.
FAU - Kaufman, Laura J
AU  - Kaufman LJ
AD  - Department of Chemistry, Columbia University, New York, NY, 10027, USA.
FAU - Wang, Xiaoyan
AU  - Wang X
AD  - Department of Cariology and Endodontology, Peking University School and Hospital 
      of Stomatology, Beijing, 100081, China.
FAU - Zhou, Yongsheng
AU  - Zhou Y
AD  - Department of Prosthodontics, Peking University School and Hospital of 
      Stomatology, Beijing, 100081, China.
FAU - Dong, Yanmei
AU  - Dong Y
AD  - Department of Cariology and Endodontology, Peking University School and Hospital 
      of Stomatology, Beijing, 100081, China.
FAU - Mao, Jeremy J
AU  - Mao JJ
AD  - Center for Craniofacial Regeneration, Columbia University, New York, NY, 10032, 
      USA.
LA  - eng
PT  - Journal Article
DEP - 20211223
PL  - China
TA  - Bioact Mater
JT  - Bioactive materials
JID - 101685294
PMC - PMC8935088
OTO - NOTNLM
OT  - Cell homing
OT  - Endogenous TGFbeta1
OT  - In situ tissue regeneration
OT  - Injectable alkaline hydrogel
OT  - Pulp-dentin complex
COIS- 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- 2022/04/01 06:00
MHDA- 2022/04/01 06:01
PMCR- 2021/12/23
CRDT- 2022/03/31 05:38
PHST- 2021/08/04 00:00 [received]
PHST- 2021/12/14 00:00 [revised]
PHST- 2021/12/14 00:00 [accepted]
PHST- 2022/03/31 05:38 [entrez]
PHST- 2022/04/01 06:00 [pubmed]
PHST- 2022/04/01 06:01 [medline]
PHST- 2021/12/23 00:00 [pmc-release]
AID - S2452-199X(21)00589-2 [pii]
AID - 10.1016/j.bioactmat.2021.12.015 [doi]
PST - epublish
SO  - Bioact Mater. 2021 Dec 23;15:316-329. doi: 10.1016/j.bioactmat.2021.12.015. 
      eCollection 2022 Sep.