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| ORIGINAL ARTICLE |
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| Year : 2014 | Volume
: 22
| Issue : 1 | Page : 33-36 |
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Untold story of collagen dressings
Mathangi K Ramakrishnan1, Mary Babu2, V Jayaraman3, T Mathivanan4
1 Kanchi Kamakoti Childs Trust Hospital, Chennai, Tamil Nadu; Banaras Hindu University, Varanasi, Uttar Pradesh, India
2 Kanchi Kamakoti Childs Trust Hospital; Central Leather Research Institute of India, Chennai, Tamil Nadu, India
3 Kilpauk Medical College, Chennai, Tamil Nadu, India
4 Kanchi Kamakoti Childs Trust Hospital, Chennai, Tamil Nadu, India
| Date of Web Publication | 15-Dec-2014 |
Correspondence Address:
Mathangi K Ramakrishnan
H.O.D, Department of Burns and Plastic Surgery, CHILDS Trust Medical Research Foundation, Kanchi Kamakoti CHILDS Trust Hospital, Chennai
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0971-653X.146998
This article tells the story of the making of collagen sheets as dressing material in India. The thought process behind the science and the methods of usage of collagen sheets have been deliberated upon. Versatility of collagen based dressings is approved by most of the surgeons and plastic surgeons for burn injuries. There have been no adverse reactions by way of allergy, or anaphylaxis. Collagen dressings are very cost-effective, less labor intensive, but the person who uses must understand the nuances thoroughly, before starting to use. It is better to learn all about the membrane prior to using it. Keywords: Amniotic membrane, biologic dressings for burns, collagen sheets
How to cite this article:
Ramakrishnan MK, Babu M, Jayaraman V, Mathivanan T. Untold story of collagen dressings. Indian J Burns 2014;22:33-6 |
| Introduction | |  |
Process of wound healing in the injured site in the skin involves multiple stages like coagulation, Inflammation, proliferation and remodeling of the injured tissue. The major players in the process are cytokines, growth factors, cells (endothelial, fibroblast and keratinocytes) and connective tissue proteins, collagen and proteoglycans. In the process of the wound healing synthesis of connective tissue during the repair must be in equilibrium with the remodeling, otherwise excessive deposition of collagen leads to thick scar tissue - Hypertrophic Scar. [1]
Description of collagen
This is a unique protein with a triple helical structure, and each helix has over 1000 aminoacids. The predominant aminoacid is glycine that constitutes 33% of the total aminoacids and hydroxyproline constitute about 10% of total acids. The essential aminoacid tryptophane is absent in all types of collagen. So far about 25 types of collagen have been identified. The main type of collagen in the skin is a type I collagen. [2]
The individual collagen molecules are cross-linked to give a stable structure to the skin. In any skin wound healing, the wound closure must be obtained as fast as possible, and this is mainly achieved by primary closure of the wound, or by skin grafting. The depth of skin and adjacent tissue dictates the type of skin graft to be used like full thickness skin, or vascularized flaps. Important aspect of wound healing is providing the best environment, lack of infection and foreign body as well as reducing the evaporative water and electrolyte loss. [3]
Wound care
To keep the wound closed primarily or with a graft, needs dressing material. Varieties of dressings (synthetic, as well as biological, are available). [4] Synthetic dressings are not very useful in tropical countries, where the skin loss (burn) is extensive. Hence the research into the types of superior dressings started in the late 1900's.
Among this group, biological dressings were thought of. A biological product that is easily available was identified as the amniotic membrane from animals and human beings. It was Robson who identified the value of amnion to heal pressure sore wounds (in 1973) [5],[6] He used bovine amniotic membrane. After hearing his deliberations at a meeting of the ISBI at Paris, Dr. Mathangi Ramakrishnan decided to try human amniotic membrane on burn patients at the burn unit of Kilpauk Medical College Hospital, Chennai [Figure 1] and [Figure 2]. With a clearance from the Ethics Committee of the same Hospital she was permitted to use human amniotic membrane from the C-Sections of mothers who were negative for HIV or hepatitis B surface antigen. [7],[8]
Since the strict laws preventing the use of body products came into existence amniotic membrane could not be used as a biologic dressing.
| Emergence of collagen based dressings | | |
Collagen from the bovine source was identified by researchers at the biomaterials Lab of Central Leather Research Institute (CLRI). Preparation of collagen membrane has two major approaches. In the first approach, the serosal layer of bovine small intestine was treated with mild enzymes, and the collagen was strengthened without disturbing the structure and cross-linking. This kind of membrane though useful was not advantageous because it has fixed configuration and size. In the second approach, the collagen was solubilized with acetic acid and purified and reconstituted in proper shape and size. [9],[10]
This membrane can be dried and sterilized and has a shelf life of 3 years. The desired porosity and size can be fabricated. This certified collagen membrane after ethics committee approval was used at the Kilpauk Medical Collage Hospital, Department of Burn and Plastic Surgery. Since then in year 1996 the process was patented with Government of India and the technology was passed on to Eucare Pharmaceuticals, who has made the membrane commercially available under the name "Kollagen."
Clinical application
This commercial collagen membrane was accepted by the medical fraternity and became a very popular cost effective burn wound dressing - both as out-patient department as well as in extensive burns in the ward.
Indications for application of collagen membrane
Superficial partial-thickness burns
As an outpatient procedure small membrane can be applied on the surface of 5-10% superficial and partial thickness burns. We use reinstituted collagen and the patient has only to wash and subject themselves to the membrane application. Once the membrane gets dried, child can be discharged and allowed to come for review [Figure 3].
Deep partial thickness burns
If the area of burn is larger than 10%, up to 20% we can remove the blister and apply the membrane after cleaning. If there is oozing of fluid within 6 h of burn, then we place a sterile gamgee dressing for 24 h, and then apply the membrane the next day [Figure 4].
Deep burns
Usually, there is no place for biologic dressings on 3 rd -degree areas. However due to lack of sufficient availability of blood, or poor general condition of the patient, or due to the cost of synthetic or commercial preparations like Integra, we may have to use closed dressings with antibiotics creams, which may get infected. As a bold step, we have used collagen dressing just as a cover on 3 rd degree wounds, or even applied after escharotomy and excision and tided over the crisis. The lessons to learn are, the availability, sterility, easy application after controlling the blood oozing are the factors which dictate the selection of biological cover - be it auto skin, homograft, Integra, membrane or collagen. We have used the latter in critical conditions, tided over the crisis, and quickly applied auto grafts. Till then, biological dressings have been useful. Examples are seen in [Figure 5] and [Figure 6]. | Figure 5: Third degree burns in a 12-year-old girl collagen membrane was used as a biologic dressing prior to excision and grafting
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 | Figure 6: Application of reconstituted bovine collagen on 30 (60%) burns after excision in a 12-year-old boy with high tension electric accident
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Complications that could arise are
- Moving of the membrane due to air bubble underneath. Milking of all the air bubbles after application is required.
- Hemorrhage under the membrane. If the oozing of blood has not been completely stopped with pressure, on the 2 nd or 3 rd day - one may find spread out clotted blood underneath. If the color of the clot is maroon and not blood red, one can leave the collagen alone and wound healing will take place.
- If we feel that the appearance is not satisfactory, under sedation the applied membrane can be removed, and fresh one can be applied as a second application also will hold well. In certain circumstances, due to poor general conditions of the burnt child, we can even do 2 or 3 membrane changes, final wound healing will be good (children particularly after membrane application do not complain of pain.)
Removal of collagen dressing
The membrane is removed with an artery forceps dipped in sterile liquid paraffin, after the patient is given mild sedation and draping. If the wound is dry, topical creams with a small amount of steroid are liberally applied. If there are small punctuate hemorrhage at the wound site, a closed sterile pressure dressing is applied. This is removed after 24 h, bath given to the patient and the patient would then be ready for discharge.
Postmembrane removal advice
- For a week to 10 days, do not face direct sunlight.
- Avoid synthetic clothes.
- Use any moisturizing cream with low dose steroid (water soluble) after removable.
- Patients have to be warned that the scars, if any occur have to be massaged daily.
- Patients have to be warned that postmembrane removal areas may become hyper pigmented. If it occurs, dermatologist can be consulted.
The plastic surgeon uses a strict protocol as to when to use, how to use, and when to remove the membrane.
Advances in the manufacture of collagen membrane dressing
Researchers and clinicians who were satisfied with the versatility of collagen, decided to make new collagen based products. For wound healing, one may require antimicrobials, growth factors and low molecular weight heparin which is antiinflammatory. CLRI incorporated silver sulfadiazine in alginate microspheres and these microspheres were loaded on collagen membrane and fabricated as a dressing. This was clinically tried out at Kanchi Kamakoti Childs Trust Hospital (Exclusive children's hospital with a burn unit) as well as in Kilpauk Medical College hospital burn unit in Chennai [Figure 7]. The results were good. The process was patented by CLRI. The process technology also was transferred to Eucare Pharmaceuticals. | Figure 7: Partial thickness burns of the chest 2 days old with surface swab positive for organisms. Hence SSD incorporated membrane was used
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Advantages
In the SSD membrane, slow drug delivery occurs, and infection settles.
| Conclusions | | |
Versatility of collagen based dressings is approved by most of the surgeons and plastic surgeons for burn injuries. There have been no adverse reactions by way of allergy, or anaphylaxis. Collagen dressings are very cost effective, less labor intensive, but the person who uses must understand the nuances thoroughly, before starting to use. It is better to learn all about the membrane prior to using it.
| Acknowledgement | | |
This work was sponsored by the "CHILDS Trust Medical Research Foundation and Kanchi Kamakoti CHILDS Trust Hospital, Chennai".
| References | | |
| 1. | Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res 2012;49:35-43.  |
| 2. | Shoulders MD, Raines RT. Collagen structure and stability. Annu Rev Biochem 2009;78:929-58. |
| 3. | Shoshan S, Gross J. Biosynthesis and metabolism of collagen and its role in tissue repair processes. Isr J Med Sci 1974;10:537-61. |
| 4. | Peters WJ. Biological dressings in burns - a review. Ann Plast Surg 1980;4:133-7. |
| 5. | Robson MC, Krizek TJ. The effect of human amniotic membranes on the bacteria population of infected rat burns. Ann Surg 1973;177:144-9. |
| 6. | Robson MC, Samburg JL, Krizek TJ. Quantitative comparison of biological dressings. J Surg Res 1973;14:431-4. |
| 7. | Ramakrishnan KM, Jayaraman V. Management of partial-thickness burn wounds by amniotic membrane: A cost-effective treatment in developing countries. Burns 1997;23 Suppl 1:S33-6. |
| 8. | Ramakrishnan KM, Doss CR, Rao DK. Human amniotic membrane as a temporary biological dressing in complicated burns a developing country. J Burn Care Rehabil 1983;4:202-4. |
| 9. | Purna SK, Babu M. Collagen based dressings - a review. Burns 2000;26:54-62. |
| 10. | Brett D. A review of collagen and collagen based wound dressings. Wounds - A compendium of clinical research and practice. 2008;20:347-56. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
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