Difference between revisions of "Team:TU Darmstadt/project/hydrogel"

Line 63: Line 63:
 
</header>
 
</header>
 
<div class="post-it">
 
<div class="post-it">
<p style="font-size:20px">ABSTRACT: We manufactured different types of chitosan hydrogels, each designed for a proper medical use. We choose to use chitosan as scaffold material due to its antimicrobial and non-toxic properties. We reached to manufacture low-cost and easy to produce hydrogels for every laboratory worldwide</p></div>
+
<p style="font-size:20px">
 +
Hydrogels are three-dimensional systems with hydrophilic polymer chains with high water content. The advantages of hydrogels are the special characteristics such as biocompatibility, elasticity and modifiable chemical properties. There are two kinds of gels, natural and synthetic. The natural ones consists of natural polysachharides which are harvested from renewable resources and are abundant, nontoxic, inexpensive and biodegradable materials. They receive an increasing attention in various fields, like medicinal research <a href="#[1]">[1]</a> <a href="#[2]">[2]</a>.
 +
<br>We want to produce such a hydrogel and modify it to detect pathogenic bacteria visually in wounds. To evaluate an ideal hydrogel, various compositions were tested, like pure chitosan or chitosan in combination with agarose, agar or alginate. During this work various promising hydrogels could be produced.
 +
</p></div>
 
</div>
 
</div>
 
</section>
 
</section>
 
<section id="two"><div class="container">
 
<section id="two"><div class="container">
  
<h3>Replace adhesive bandages for patients</h3>
+
<h3>Introduction</h3>
<p>We want to detect pathogenic bacteria visually in wounds, which is not possible with standard adhesive bandages. If you want to monitor the wound healing process you would have to remove the common bandages and take samples and then check these samples for pathogenic bacteria in a specialized laboratory, a long time and expensive process. A hydrogel is characterized by containing water, forms a solid three-dimensional network structures and is water insoluble. Most Hydrogels could swell in aqueous solutions, for our purpose as a wound bandage it is possible to absorb some of the wound fluid. The hydrogels could airtight the affected wounds and therefore helps the healing process.
+
<p>Patients with burn wounds or other poor-healing wounds, like diabetes wounds, often suffer from various complications such as infections. Until now the common medical bandages have to be removed to monitor the wound healing progress. To examine if there is an infection, which implies the presence of pathogenic bacteria, samples of the wound have to be taken and studied in a specialized laboratory. This is a long time and expensive process and we want to simplify and accelerate this procedure.
Our hydrogels are designed for patients with burns or as a special health care product for patients with bad wound healing, for example diabetes patients. We can deliver an optimal wound healing and monitoring bandage for these affected patients without the need to disrupt the healing process.
+
The solution for the problem is a hydrogel, which is characterized by containing water, forming a solid three-dimensional network structures and being water insoluble. Most hydrogels could swell in aqueous solutions; for our purpose, as a wound bandage, it can be used to absorb some of the wound fluid. Furthermore it can be attached hermetically and the moisture provided by the hydrogel leads therefore to ideal wound healing conditions.
</p>
+
An optimal polymer for such a hydrogel is chitosan (poly-1,4-β-D-glucopyranosamine). It has beneficial properties like biocompatibility, biodegradability, and film forming ability. Furthermore, chitosan has reactive amine side groups, which offer possibilities for modifications, like the linkage of a fluorophore to detect the pathogenic bacteria. <a href="#[2]">[2]</a>
 
+
<br>The hemostatic chitosan is reported to have intrinsic antifungal, antibacterial, and antiviral properties. Furthermore it promotes scar free wound healing and has care effects, and is antiallergic <a href="#[3]">[3]</a>. In addition human epithelium could heal along the chitosan matrix, so no wound distance grid is necessary <a href="#[1]">[1]</a>. It is an ideal scaffold material to manufacture different types of hydrogels, salves, pastes or solid bandages. Besides its great described antimicrobial characteristics, it has a skin cooling effects. Most chitosan hydrogel topical wound dressings are formed using an expensive or toxic crosslinking agent, which we want to avoid.
<details>
+
<summary>More Informations</summary>
+
<p>During the swelling it could absorb the fluid of ulcer as well as for strong exuding wounds</p>
+
</details>
+
 
+
 
<br>
 
<br>
<h3>Why use our hydrogels?</h3>
+
<br>Due to that we can deliver an optimal wound healing and monitoring bandage for these affected patients without the need to disrupt the healing process. The hydrogel should help preventing or treat wound infections of any degree of burns.
<p>The hydrogel(s) we wanted to create are due to their compounds not toxic, biodegradable, biocompatible, while at the same time having a low-cost and easy to manufacturing processes.
+
They are easy to produce in different sizes. While being flexible they keep their stability, which makes it comfortable for patients to wear, and easy to manufacture, handle and apply on patients.
+
We chose the hemostatic chitosan due to its reported intrinsic antifungal, antibacterial and antiviral properties. Chitosan as wound dressing has scar free, excellent wound heal and care effects.  
+
The antiallergic chitosan is an ideal scaffold material to manufacture different types of hydrogels, salves, pastes or solid bandages. Besides its great described antimicrobial characteristics, it has a skin cooling effects. Most chitosan hydrogel topical wound dressings are formed using an expensive or toxic crosslinking agent, we aimed not to use any of these compounds. We could help preventing or treat wound infections of any degree of burns.</p>
+
  
 +
</p>
 +
</div></div>
 +
</section>
 +
<section id="three"><div class="container">
  
<details>
+
<h3>Production</h3>
<summary>More Informations</summary>
+
<p>To evaluate an ideal hydrogel, various compositions were tested, like pure chitosan or chitosan in combination with agarose, agar or alginate. During this work various promising hydrogels could be produced.
<p>The pH-level of some of our hydrogels are easy to regulate by rinsing it with the proper pH-level solution.</p>
+
The kind of hydrogels we want to create are due to their compounds not toxic, biodegradable, biocompatible, while at the same time having a low-cost and easy to manufacturing processes. They are easy to produce in different sizes and thicknesses. While being flexible they keep their stability, which makes it comfortable for patients to wear, and easy to manufacture, handle and apply on patients.
<p>Human epitel could heal along the chitosan matrix, no wound distance grid is necessary. The moisture provided by our hydrogels could also help the wound healing process</p>
+
The pH-level of some of our hydrogels are easy to regulate by rinsing it with the proper pH-level solution.
</details>
+
We were focused to work with basic laboratory equipment. For the preparation of chitosan hydrogels, an acidic environment is usually required to dissolve chitosan. We manufactured our chitosan containing hydrogel in aqueous acetic acid.
 +
</p>
 +
 
 +
<h4>Chitosan-Alginate</h4>
 +
<p>A long time continuous mechanical stirring (6 hours) is required to dissolve the chitosan in the acetic acid-deionized water solution. Under continuous pH measurement it was mechanically stirred for 12 hours. This solution needs to rest for at least 12 hours for further processing.</p>
  
<br>
 
<h3>Production of our chitosan-hydrogels</h3>
 
<p>We were focused to work with basic laboratory equipment. For the preparation of chitosan hydrogels, an acidic environment is usually required to dissolve chitosan. We used in our manufacturing processes chitosan with a high molecular weight
 
(310000-375000 Da) and a deacetylated patter of >75%. It took several days to figure out the composition of the specific hydrogel(s) we wanted to use for different potential medical applications. A long time continuous mechanical stirring (6 hours) is required to solve the chitosan in the acetic acid-deionized water solution. Under continuous pH measurement it was mechanically stirred constantly for 12 hours. This solution needs to rest for at least 12 hours for further processing. To change a certain pH-level we added more or less acetic acid at the chitosan solving step.</p>
 
  
  
Line 151: Line 149:
 
</figure>
 
</figure>
  
 +
</div></div>
 +
</section>
 +
<section id="four"><div class="container">
 +
<h4>Chitosan-Agarose</h4>
 +
<p>A hydrogel composed of chitosan and agarose fulfils most of the required criteria for an “ideal” wound dressing.
 +
Agarose is a biocompatible, linear polysaccharide which is extracted from marine algae. It consists of 1,4-linked 3,6-anhydro-α-L-galactose and 1,3-linked β-D-galactose derivatives.
 +
<br>When the agarose is dissolved in water, it forms a gel with a three-dimensional scaffold and a porous structure providing a good environment for cell adhesion, spreading and proliferation. It is capable of gelling within the desired site because of the polymer interaction. By varying the concentration of agarose in the hydrogel, the mechanical properties, which are similar to those of tissues, can easily be adjusted <a href="#[4]">[4]</a>.
 +
<br>The preparation of such a hydrogel is quite simple. The desired amount of agarose is dissolved in water. 1 % acetic acid and the desired amount of chitosan are dissolved in water, simultaneously. Both solution are mixed and heated while stirring until the solution is clear. We transferred this mixture in a petri dish with the desired thickness.
 +
We examined gels with concentrations of 1 -3 % agarose and 1 – 3 % chitosan. The most promising variation was the hydrogel with 1 % agarose and 1 % chitosan. It forms a stable, elastic gel which allows easy handling.
 +
The simplicity of preparing the hydrogel and its multifunctionality allows many future applications of agarose-based hydrogels <a href="#[5]">[5]</a>.
 +
</p>
  
 +
<h4>Chitosan-Agar</h4>
 +
<p>The mixture of chitosan with agar forms hydrogels with enhanced swelling compared to pure chitosan ones.
 +
Agar is a hydrophilic cell-wall polysaccharide extracted from the family of seaweeds. It composes of alternating (1-4)-D-galactose and (1-3)-3,6-anhydro-L-galactose repeating units and forms reversible gels even with a low concentration because of the formation of hydrogen bonds<a href="#[2]">[2]</a><a href="#[6]">[6]</a>. It is soluble in hot water and forms a gel during cooling. The polymer is biodegradable, low-cost, environmentally friendly and easy to extract. It is already used in pharmaceutical industry as a gelling, stabilizing and encapsulating agent <a href="#[7]">[7]</a>.
 +
The preparation is the same procedure as for agarose, just with agar instead of the agarose.
 +
The most promising variation was, as well as with agarose, the hydrogel with 1 % agar and 1 % chitosan. It forms a stable, elastic gel which allows easy handling.
 +
</p>
 
</div>
 
</div>
 
  
  
 
</div>
 
</div>
 
     </section>
 
     </section>
 +
 +
</div>
 +
    </section>
 +
 +
 +
<section id="seven"><div class="container">
 +
<h3>References</h3>
 +
<p>
 +
<table width="100%" border="0" cellpadding="0" cellspacing="2">
 +
<tr>
 +
  <td id="[1]">[1]</td>
 +
  <td>Tsou, Y. H., Khoneisser, J., Huang, P. C., and Xu, X. (2016) Hydrogel as a bioactive material to regulate stem cell fate. <i>Bioactive Materials</i>, 1, 29 – 55
 +
<br>DOI: 10.1016/j.bioactmat.2016.05.001</td>
 +
</tr>
 +
<tr>
 +
  <td id="[2]">[2]</td>
 +
  <td>El-Hefian, E. A., Nasef, M. M., and Yahaya, A. H. (2012) Preparation and Characterization of Chitosan/Agar Blended Films: Part 1. Chemical Structure and Morphology. <i>E-Journal of Chemistry</i>, 9, 1431 - 1439
 +
<br>DOI: 10.1155/2012/781206
 +
</td>
 +
</tr>
 +
<tr>
 +
  <td id="[3]">[3]</td>
 +
  <td>Ahsan, S. M., Thomas, M., Reddy, K. K., Sooraparaju, S. G., Asthana, A., and Bhatnagar, I. (2017) Chitosan as biomaterial in drug delivery and tissue engineering. <i>International Journal of Biological Macromolecules<i>/, In Press
 +
<br>DOI: 10.1016/j.ijbiomac.2017.08.140
 +
</td>
 +
</tr>
 +
<tr>
 +
  <td id="[4]">[4]</td>
 +
  <td>Miguel, S. P., Ribeiro, M. P., Brancal, H., Coutinho, P., and Correia, I. J. (2014) Thermoresponsive chitosan-agarose hydrogel for skin regeneration. <i>Carbohydrate Polymers</i>, 111, 366 – 373
 +
<br>DOI: 10.1016/j.carbpol.2014.04.093
 +
  </td>
 +
</tr>
 +
<tr>
 +
  <td id="[5]">[5]</td>
 +
  <td>Cao, Z., Gilbert, R. J., and He, W. (2009) Simple Agarose-Chitosan Gel Composite System for Enhanced Neuronal Growth in Three Dimensions. <i>Biomacromolecules</i>, 10, 2954 – 2959
 +
<br>DOI: 10.1021/bm900670n
 +
</td>
 +
</tr>
 +
<tr>
 +
  <td id="[6]">[6]</td>
 +
  <td>El-Hefian, E. A., Nasef, M. M., and Yahaya, A. H. (2012) Preparation and Characterization of Chitosan/Agar Blended Films: Part 2. Thermal, Mechanical, and Surface Properties. <i>E-Journal of Chemistry</i>, 9, 510 – 516
 +
<br>DOI: 10.1155/2012/285318
 +
</td>
 +
</tr>
 +
<tr>
 +
  <td id="[7]">[7]</td>
 +
  <td>Sousa, A. M. M., Sereno, A. M., Hilliou, L., and Goncalves, M. P. (2010) Biodegradable Agar extracted from <i>Gracilaria Vermiculophylla</i>: Film Properties and Application to Edible Coating. <i>Materials Science Forum</i>, 636-637, 739 – 744
 +
<br>DOI: 10.4028/www.scientific.net/MSF.636-637.739
 +
</td>
 +
</tr>
  
 
<!-- Footer -->
 
<!-- Footer -->

Revision as of 15:03, 15 October 2017

MainPage

The Hydrogels

Hydrogels are three-dimensional systems with hydrophilic polymer chains with high water content. The advantages of hydrogels are the special characteristics such as biocompatibility, elasticity and modifiable chemical properties. There are two kinds of gels, natural and synthetic. The natural ones consists of natural polysachharides which are harvested from renewable resources and are abundant, nontoxic, inexpensive and biodegradable materials. They receive an increasing attention in various fields, like medicinal research [1] [2].
We want to produce such a hydrogel and modify it to detect pathogenic bacteria visually in wounds. To evaluate an ideal hydrogel, various compositions were tested, like pure chitosan or chitosan in combination with agarose, agar or alginate. During this work various promising hydrogels could be produced.

Introduction

Patients with burn wounds or other poor-healing wounds, like diabetes wounds, often suffer from various complications such as infections. Until now the common medical bandages have to be removed to monitor the wound healing progress. To examine if there is an infection, which implies the presence of pathogenic bacteria, samples of the wound have to be taken and studied in a specialized laboratory. This is a long time and expensive process and we want to simplify and accelerate this procedure. The solution for the problem is a hydrogel, which is characterized by containing water, forming a solid three-dimensional network structures and being water insoluble. Most hydrogels could swell in aqueous solutions; for our purpose, as a wound bandage, it can be used to absorb some of the wound fluid. Furthermore it can be attached hermetically and the moisture provided by the hydrogel leads therefore to ideal wound healing conditions. An optimal polymer for such a hydrogel is chitosan (poly-1,4-β-D-glucopyranosamine). It has beneficial properties like biocompatibility, biodegradability, and film forming ability. Furthermore, chitosan has reactive amine side groups, which offer possibilities for modifications, like the linkage of a fluorophore to detect the pathogenic bacteria. [2]
The hemostatic chitosan is reported to have intrinsic antifungal, antibacterial, and antiviral properties. Furthermore it promotes scar free wound healing and has care effects, and is antiallergic [3]. In addition human epithelium could heal along the chitosan matrix, so no wound distance grid is necessary [1]. It is an ideal scaffold material to manufacture different types of hydrogels, salves, pastes or solid bandages. Besides its great described antimicrobial characteristics, it has a skin cooling effects. Most chitosan hydrogel topical wound dressings are formed using an expensive or toxic crosslinking agent, which we want to avoid.

Due to that we can deliver an optimal wound healing and monitoring bandage for these affected patients without the need to disrupt the healing process. The hydrogel should help preventing or treat wound infections of any degree of burns.

Production

To evaluate an ideal hydrogel, various compositions were tested, like pure chitosan or chitosan in combination with agarose, agar or alginate. During this work various promising hydrogels could be produced. The kind of hydrogels we want to create are due to their compounds not toxic, biodegradable, biocompatible, while at the same time having a low-cost and easy to manufacturing processes. They are easy to produce in different sizes and thicknesses. While being flexible they keep their stability, which makes it comfortable for patients to wear, and easy to manufacture, handle and apply on patients. The pH-level of some of our hydrogels are easy to regulate by rinsing it with the proper pH-level solution. We were focused to work with basic laboratory equipment. For the preparation of chitosan hydrogels, an acidic environment is usually required to dissolve chitosan. We manufactured our chitosan containing hydrogel in aqueous acetic acid.

Chitosan-Alginate

A long time continuous mechanical stirring (6 hours) is required to dissolve the chitosan in the acetic acid-deionized water solution. Under continuous pH measurement it was mechanically stirred for 12 hours. This solution needs to rest for at least 12 hours for further processing.

Chitosan Hydrogel solidified in Alginate-Quercetin solution


The alginate/quercetin solution was poured into a mold and then liquid-friezed. The 2% chitosan solution was then poured onto it and streaked out to the certain thickness, covered with the alginate/quercetin solution, placed into the 37° incubator for 24 hours.


After the solidification process the arosed solid hydrogel was rinsed with ultrapure water. Placed into an aqueous solution it will swell massively after time.
DS Ww - Wd Ww x100
The bandages were saturated with the liquid in which it was immersed. Our manufactured hydrogel has a degree of swelling of 800.


Chitosan Hydrogel with high pH-level

Manufacturing process of our chitosan hydrogel with a high pH-level was performed by rinsing the 2% chitosan solution with a defined NaOH solution with the desired pH-level.


Produced hydrogel rinsed with NaOH solution(pH 10) (left). Transparency shown (right)

Chitosan-Agarose

A hydrogel composed of chitosan and agarose fulfils most of the required criteria for an “ideal” wound dressing. Agarose is a biocompatible, linear polysaccharide which is extracted from marine algae. It consists of 1,4-linked 3,6-anhydro-α-L-galactose and 1,3-linked β-D-galactose derivatives.
When the agarose is dissolved in water, it forms a gel with a three-dimensional scaffold and a porous structure providing a good environment for cell adhesion, spreading and proliferation. It is capable of gelling within the desired site because of the polymer interaction. By varying the concentration of agarose in the hydrogel, the mechanical properties, which are similar to those of tissues, can easily be adjusted [4].
The preparation of such a hydrogel is quite simple. The desired amount of agarose is dissolved in water. 1 % acetic acid and the desired amount of chitosan are dissolved in water, simultaneously. Both solution are mixed and heated while stirring until the solution is clear. We transferred this mixture in a petri dish with the desired thickness. We examined gels with concentrations of 1 -3 % agarose and 1 – 3 % chitosan. The most promising variation was the hydrogel with 1 % agarose and 1 % chitosan. It forms a stable, elastic gel which allows easy handling. The simplicity of preparing the hydrogel and its multifunctionality allows many future applications of agarose-based hydrogels [5].

Chitosan-Agar

The mixture of chitosan with agar forms hydrogels with enhanced swelling compared to pure chitosan ones. Agar is a hydrophilic cell-wall polysaccharide extracted from the family of seaweeds. It composes of alternating (1-4)-D-galactose and (1-3)-3,6-anhydro-L-galactose repeating units and forms reversible gels even with a low concentration because of the formation of hydrogen bonds[2][6]. It is soluble in hot water and forms a gel during cooling. The polymer is biodegradable, low-cost, environmentally friendly and easy to extract. It is already used in pharmaceutical industry as a gelling, stabilizing and encapsulating agent [7]. The preparation is the same procedure as for agarose, just with agar instead of the agarose. The most promising variation was, as well as with agarose, the hydrogel with 1 % agar and 1 % chitosan. It forms a stable, elastic gel which allows easy handling.

References

[1] Tsou, Y. H., Khoneisser, J., Huang, P. C., and Xu, X. (2016) Hydrogel as a bioactive material to regulate stem cell fate. Bioactive Materials, 1, 29 – 55
DOI: 10.1016/j.bioactmat.2016.05.001
[2] El-Hefian, E. A., Nasef, M. M., and Yahaya, A. H. (2012) Preparation and Characterization of Chitosan/Agar Blended Films: Part 1. Chemical Structure and Morphology. E-Journal of Chemistry, 9, 1431 - 1439
DOI: 10.1155/2012/781206
[3] Ahsan, S. M., Thomas, M., Reddy, K. K., Sooraparaju, S. G., Asthana, A., and Bhatnagar, I. (2017) Chitosan as biomaterial in drug delivery and tissue engineering. International Journal of Biological Macromolecules/, In Press
DOI: 10.1016/j.ijbiomac.2017.08.140
[4] Miguel, S. P., Ribeiro, M. P., Brancal, H., Coutinho, P., and Correia, I. J. (2014) Thermoresponsive chitosan-agarose hydrogel for skin regeneration. Carbohydrate Polymers, 111, 366 – 373
DOI: 10.1016/j.carbpol.2014.04.093
[5] Cao, Z., Gilbert, R. J., and He, W. (2009) Simple Agarose-Chitosan Gel Composite System for Enhanced Neuronal Growth in Three Dimensions. Biomacromolecules, 10, 2954 – 2959
DOI: 10.1021/bm900670n
[6] El-Hefian, E. A., Nasef, M. M., and Yahaya, A. H. (2012) Preparation and Characterization of Chitosan/Agar Blended Films: Part 2. Thermal, Mechanical, and Surface Properties. E-Journal of Chemistry, 9, 510 – 516
DOI: 10.1155/2012/285318
[7] Sousa, A. M. M., Sereno, A. M., Hilliou, L., and Goncalves, M. P. (2010) Biodegradable Agar extracted from Gracilaria Vermiculophylla: Film Properties and Application to Edible Coating. Materials Science Forum, 636-637, 739 – 744
DOI: 10.4028/www.scientific.net/MSF.636-637.739