PMID- 31103676
OWN - NLM
STAT- MEDLINE
DCOM- 20200910
LR  - 20211207
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 305
DP  - 2019 Jul 10
TI  - Distinct release strategies are required to modulate macrophage phenotype in 
      young versus aged animals.
PG  - 65-74
LID - S0168-3659(19)30268-8 [pii]
LID - 10.1016/j.jconrel.2019.05.020 [doi]
AB  - The role of innate immunity and macrophages in the host response to biomaterials 
      has received renewed attention. A context-dependent spectrum of macrophage 
      phenotypes are shown to affect tissue integration and performance of implanted 
      biomaterials and medical devices. Recent studies by our group demonstrated that 
      the host response in aged animals was characterized by delayed macrophage 
      recruitment, differences in marker expression and a shifted pro-inflammatory (M1) 
      response, associated with an unresolved host response in the long-term. The 
      present work sought to study the effects of single and sequential cytokine 
      delivery regimens in aged mice to restore delayed recruitment of macrophages and 
      shift the inflammatory host response towards an M2-like phenotype, using MCP-1 
      (macrophage chemotactic protein-1) and IL-4 (interleukin-4), respectively. 
      Implantation of cytokine-eluting implants showed a preserved response to MCP-1 in 
      both young and aged animals, restoring delayed macrophage recruitment in aged 
      mice. However, the response elicited by IL-4, sequential delivery of MCP-1/IL-4 
      and coating components was distinct in young versus aged mice. While single 
      delivery of IL-4 did not counteract the high inflammatory response observed in 
      aged mice, the sequential delivery of MCP-1/IL-4 was capable of restoring both 
      recruitment and shifting the macrophage response towards an M2-like phenotype, 
      associated with decreased implant scarring in the long-term. In young mice, 
      sequential delivery was not as effective as IL-4 alone at promoting an M2-like 
      response, but did result in a reduction of M1 macrophages and capsule deposition 
      downstream. These results demonstrate that a proper understanding of 
      patient/context-dependent biological responses are needed to design 
      biomaterial-based therapies with improved outcomes in the setting of aging.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Hachim, Daniel
AU  - Hachim D
AD  - McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 
      Technology Drive, Suite 300, Pittsburgh, PA 15219, United States of America; 
      Department of Bioengineering, Swanson School of Engineering, University of 
      Pittsburgh, 302 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15260, United 
      States of America.
FAU - Iftikhar, Aimon
AU  - Iftikhar A
AD  - McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 
      Technology Drive, Suite 300, Pittsburgh, PA 15219, United States of America; 
      Department of Bioengineering, Swanson School of Engineering, University of 
      Pittsburgh, 302 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15260, United 
      States of America.
FAU - LoPresti, Samuel T
AU  - LoPresti ST
AD  - McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 
      Technology Drive, Suite 300, Pittsburgh, PA 15219, United States of America; 
      Department of Bioengineering, Swanson School of Engineering, University of 
      Pittsburgh, 302 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15260, United 
      States of America.
FAU - Nolfi, Alexis L
AU  - Nolfi AL
AD  - McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 
      Technology Drive, Suite 300, Pittsburgh, PA 15219, United States of America; 
      Department of Bioengineering, Swanson School of Engineering, University of 
      Pittsburgh, 302 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15260, United 
      States of America.
FAU - Ravichandar, Shweta
AU  - Ravichandar S
AD  - McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 
      Technology Drive, Suite 300, Pittsburgh, PA 15219, United States of America; 
      Department of Bioengineering, Swanson School of Engineering, University of 
      Pittsburgh, 302 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15260, United 
      States of America.
FAU - Skillen, Clint D
AU  - Skillen CD
AD  - McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 
      Technology Drive, Suite 300, Pittsburgh, PA 15219, United States of America.
FAU - Brown, Bryan N
AU  - Brown BN
AD  - McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 
      Technology Drive, Suite 300, Pittsburgh, PA 15219, United States of America; 
      Department of Bioengineering, Swanson School of Engineering, University of 
      Pittsburgh, 302 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15260, United 
      States of America; Department of Obstetrics, Gynecology and Reproductive 
      Sciences, University of Pittsburgh, 300 Halket Street, Pittsburgh, PA 15213, 
      United States of America. Electronic address: brownb@upmc.edu.
LA  - eng
GR  - K12 HD043441/HD/NICHD NIH HHS/United States
GR  - R01 AG055564/AG/NIA NIH HHS/United States
GR  - T32 EB001026/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190517
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Chemokine CCL2)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Aging
MH  - Animals
MH  - Chemokine CCL2/*administration & dosage/pharmacology
MH  - Drug Delivery Systems
MH  - Drug Liberation
MH  - Inflammation/immunology/prevention & control
MH  - Interleukin-4/*administration & dosage/pharmacology
MH  - Macrophages/*drug effects/immunology
MH  - Mice, Inbred C57BL
MH  - Prostheses and Implants
PMC - PMC6602858
MID - NIHMS1530107
OTO - NOTNLM
OT  - Aging
OT  - Biomaterials
OT  - Cytokine
OT  - Delivery
OT  - Host response
OT  - IL-4
OT  - MCP-1
OT  - Macrophage
OT  - Sequential
EDAT- 2019/05/20 06:00
MHDA- 2020/09/12 06:00
PMCR- 2020/07/10
CRDT- 2019/05/20 06:00
PHST- 2019/01/15 00:00 [received]
PHST- 2019/04/09 00:00 [revised]
PHST- 2019/05/13 00:00 [accepted]
PHST- 2019/05/20 06:00 [pubmed]
PHST- 2020/09/12 06:00 [medline]
PHST- 2019/05/20 06:00 [entrez]
PHST- 2020/07/10 00:00 [pmc-release]
AID - S0168-3659(19)30268-8 [pii]
AID - 10.1016/j.jconrel.2019.05.020 [doi]
PST - ppublish
SO  - J Control Release. 2019 Jul 10;305:65-74. doi: 10.1016/j.jconrel.2019.05.020. 
      Epub 2019 May 17.