There are multifold challenges in making ideal tissue adhesives for multipurpose use. Some issues that need to be addressed for actual implementation are wet adhesion, biocompatibility and safety of the adhesive materials, degradability without producing dangerous byproducts to the physical body, ease of accessibility, and use of in clinical environment, and last but not least the cost. The recommendations based on future works that need to be done are listed below:
1. Enriching platelet-rich plasma by fractionation to reduce clotting time
2. In vivo toxicity tests using mice or rabbits can be performed for safety concerns.
3. Adhesion strength tests can be performed on actual human skins or skin grafts using a Universal Testing Machine (UTM).
4. Various types of blood tests like platelet count, hemoglobin level, etc. can be performed using blood from multiple donors to determine their correlation with adhesion time and strength of the fibrin glue.
66 5. More experiments may need to be completed by varying the concentration of the polymer and mix various polymers in different ratios to enhance the strength of the fibrin glue.
67
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Appendix A : Data Tables
Table A.1: Determination of Clotting Time of Autologous Fibrin Glue Plasma Type/Polymer
Concentration Frozen Plasma Fresh
Plasma 1.25%
CMC 0.6250%
CMC 0.3125%
CMC 1.25%
MC 0.6250%
MC 0.3125%
MC Calcium Chloride
Concentration (% w/v) 5% 10% 20% 10% 10% 10% 10% 10% 10% 10%
3.00 6.83 5.17 4.83 4.50 6.62 2.65
6.75 2.88 4.03 2.42 4.00 3.28 4.33 4.25
18.00 13.50 41.00 6.75 5.33 5.75 5.17 6.83 4.83 5.17
19.00 20.00 43.00 6.83 5.92 5.83 3.67 1.98 4.33 2.48
11.50 16.67 48.00 6.17
18.00 13.67 33.50 3.83
10.50 16.50 50.00 6.02
8.53 4.58
8.67 14.00
6.17 53.65 11.67
13.90 11.67
Average Clotting Time (m) 15.40 12.91 44.86 5.01 5.53 4.79 4.42 4.15 5.03 3.64 Standard Deviation
(SAMPLE) 4.05 4.09 7.22 1.64 1.17 1.61 0.70 2.07 1.08 1.29
Count (n) 5.00 13.00 6.00 8.00 4.00 4.00 4.00 4.00 4.00 4.00
Standard Error Mean 1.81 1.14 2.95 0.58 0.59 0.81 0.35 1.03 0.54 0.65
72 Table A.2: Determination of Adhesion Strength of Autologous Fibrin Glue
Plasma Type/Polymer Concentration
Adhesion Strength (g/cm2) Plasma Bag Fresh
Plasma 1.25%
CMC 0.6250%
CMC 0.3125%
CMC 1.25%
MC 0.6250%
MC 0.3125%
MC Calcium Chloride
Concentration (% w/v) 5% 10% 20% 10% 10% 10% 10% 10% 10% 10%
66.20 65.20 24.20 41.21 51.39 82.13 71.23 112.19 80.89 60.85
34.20 42.20 54.20 41.36 55.88 79.33 72.50 108.50 83.25 59.50
38.20 57.28 81.25 61.13 98.25 79.61 62.15
38.12 60.07 43.20 Average Adhesion
Strength (g/cm2) 46.17 55.82 40.53 40.26 54.85 80.90 68.28 106.31 81.25 60.83
Standard Deviation
(SAMPLE) 17.45 12.07 15.18 1.78 3.08 1.43 6.23 7.22 1.85 1.33
Count (n) 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00
Standard Error Mean 10.08 6.97 8.76 1.03 1.78 0.83 3.60 4.17 1.07 0.77
73 Table A.3: Determination of heating effect on Autologous Fibrin Glue
Plasma Source Clotting Time(m)
Without applying heat Applying heat
Donor Plasma 4.50 3.00
Frozen Plasma from Blood
Bank 8.63 3.70
Frozen Plasma from Blood
Bank 16.00 8.00
Table A.4: Determination of Water Content
Sample Type Initial
Weight, Wi (g)
Lyophilized Weight,
Wd (g)
Water content (%)
Blank (Fresh Plasma) 36.65 36.11 1.47
MC-0.3125 39.66 38.93 1.85
MC-0.6250 18.96 18.65 1.64
MC-1.25 18.62 18.44 0.96
CMC-0.3125 39.37 39.23 0.35
CMC-0.6250 39.38 39.14 0.62
CMC-1.25 39.34 39.21 0.34
74 Table A.5: Determination of Cytotoxicity of Polymers
Sample Concentration
(%w/v) Absorbance (@490 nm) Cell Viability Control (Deionized (%)
Water) - 2.922 3.436 100
Methylcellulose
0.3125 2.834 3.126 93.74
0.6250 2.5 2.381 76.77
1.25 2.282 2.532 75.72
2.50 2.122 2.202 68.01
Sodium carboxymethyl cellulose
0.3125 2.316 2.613 77.52
0.6250 2.17 2.391 71.74
1.25 2.216 2.183 69.19
2.50 2.005 2.113 64.77
75
Appendix B : Instrumental Setup
Figure B.1: Custom Tensile Testing Machine with Modifications
Figure B.2: Custom Digital Thermometer with Multiple Probes
76 Figure B.4: Before and After Freeze Drying
Figure B.3: Freeze Drying Machine (BCSIR)
77 Figure B.5: Gold Sputtering device and SEM with EDS Machine
78
Appendix C : Fibrin Glue Market
Fibrin Glue Global market
Some of the major companies operating in the global fibrin glue market are Haemacure, Cryolife, Inc., Baxter International Inc., Vivostat A/S, Omrix Biopharmaceutical Inc., Harvest Technologies, CSL Behring, and Interpore Cross(Aryan Mishra n.d.)
Fibrin Glue Market Breakdown By Geography
➢ North America o U.S
o Canada
o Rest of North America
➢ Europe o U.K.
o Germany o France o Italy o Spain o Russia
o Rest of Europe
➢ Asia o India o China o Japan o Rest of Asia
➢ ROW
o Australia o Brazil