PMID- 33440484
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210114
IS  - 2373-9878 (Electronic)
IS  - 2373-9878 (Linking)
VI  - 2
IP  - 5
DP  - 2016 May 9
TI  - Factorial Design of Experiments to Optimize Multiple Protein Delivery for Cardiac 
      Repair.
PG  - 879-886
LID - 10.1021/acsbiomaterials.6b00146 [doi]
AB  - Myocardial infarction (MI) is a major cardiovascular disease responsible for 
      millions of deaths annually. Protein therapies can potentially repair and 
      regenerate the infarcted myocardium. However, because of the short half-lives of 
      proteins in vivo, their low retention at the target tissue, and the lack of 
      spatiotemporal cues upon injection, the efficacy of protein therapy can be 
      limited. This efficacy can be improved by utilizing controlled release systems to 
      overcome shortcomings associated with a direct bolus injection. Equally important 
      is the determination of an optimal combination of different proteins having 
      distinct roles in cardiac function and repairs to prevent or reverse the multiple 
      pathologies that develop after infarction. In this work, we used a rat MI model 
      to test a combination of potentially complementary proteins: tissue inhibitor of 
      metalloproteinases 3 (TIMP-3), interleukin-10 (IL-10), basic fibroblast growth 
      factor (FGF-2), and stromal cell-derived factor 1 alpha (SDF-1alpha). To achieve 
      controlled and timed release of the proteins per their physiologic cues during 
      proper tissue repair, we used a fibrin gel-coacervate composite. TIMP-3 and IL-10 
      were encapsulated in fibrin gel to offer early release, while FGF-2 and SDF-1alpha 
      were encapsulated in heparin-based coacervates and distributed in the same fibrin 
      gel to offer sustained release. We utilized a powerful statistical tool, 
      factorial design of experiments (DOE), to refine this protein combination based 
      on its improvement of ejection fraction 4 weeks after MI. We found that TIMP-3, 
      FGF-2, and SDF-1alpha demonstrated significant contributions toward improving the 
      ejection fraction, while the IL-10's effect was insignificant. The results also 
      suggested that the higher doses tested for TIMP-3, FGF-2, and SDF-1alpha had greater 
      benefit on function than lower doses and that there existed slight antagonism 
      between TIMP-3 and FGF-2. Taken together, we conclude that factorial DOE can 
      guide the evolution of multiple protein therapies in a small number of runs, 
      saving time, money, and resources for finding the optimal dose and composition.
FAU - Awada, Hassan K
AU  - Awada HK
FAU - Johnson, Louis A
AU  - Johnson LA
AD  - SnapDat Inc., 733 West Foster Avenue, State College, Pennsylvania 16801, United 
      States.
FAU - Hitchens, T Kevin
AU  - Hitchens TK
FAU - Foley, Lesley M
AU  - Foley LM
FAU - Wang, Yadong
AU  - Wang Y
LA  - eng
PT  - Journal Article
DEP - 20160429
PL  - United States
TA  - ACS Biomater Sci Eng
JT  - ACS biomaterials science & engineering
JID - 101654670
SB  - IM
OTO - NOTNLM
OT  - coacervate
OT  - controlled release
OT  - factorial design
OT  - fibrin gel
OT  - myocardial infarction
OT  - proteins
EDAT- 2016/05/09 00:00
MHDA- 2016/05/09 00:01
CRDT- 2021/01/14 01:00
PHST- 2021/01/14 01:00 [entrez]
PHST- 2016/05/09 00:00 [pubmed]
PHST- 2016/05/09 00:01 [medline]
AID - 10.1021/acsbiomaterials.6b00146 [doi]
PST - ppublish
SO  - ACS Biomater Sci Eng. 2016 May 9;2(5):879-886. doi: 
      10.1021/acsbiomaterials.6b00146. Epub 2016 Apr 29.