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Methods to enhance wound healing and enhanced wound coverage material

a wound and material technology, applied in the field of trauma medicine and wounds, can solve the problems of high cost of materials, poor extended outcome, poor safety, etc., and achieve the effects of improving wound healing, enhancing wound healing, and enhancing wound coverag

Inactive Publication Date: 2002-09-12
RES DEVMENT FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0015] The present invention describes a method of enhanced wound healing using liposomes carrying genes encoding growth-enhancing agents. The present invention further describes an enhanced wound coverage material impregnated with liposomes carrying genes expressing growth factors to improve wound healing. It is an object of the present invention to decrease the hypermetabolic response, and thus, improve the clinical outcome and increase the survivability after trauma, particularly thermal injury.
[0016] The present invention describes the incorporation of liposomal gene constructs directly into a wound and / or into the coverage material to improve wound repair and enhance the functionality of the wound coverage material. The present invention further describes the use of enhanced fetal human amnion membrane, in conjunction with liposomal gene constructs expressing growth factors, as a transient wound coverage material in full-thickness wound repair. Fetal membrane has advantages over currently used materials, such as Integra.TM., Biobrane.TM., Alloderm.TM., and is an efficient and safe approach to improve clinical outcome.
[0017] One object of the present invention is to provide methods to enhance wound healing, methods to enhance wound coverage material and an enhanced wound coverage material.

Problems solved by technology

The larger the burn injury, the more severe the consequences and the higher the chance of poor extended outcomes and death.
Autologous skin can be used to graft the excised wound (donor-site), however, this is not an effective treatment in patients with especially large burns.
However, these materials are very expensive, which limits their widespread use.
However, the risk of transmission of HIV, CMV, HSV and hepatitis is a significant concern, and therefore, limits application of cadaver skin.
There are adverse side effects, such as hypoglycemia, mental status changes, edema, fatigue and headache, which limit the therapeutic utility of IGF-I in the treatment of burns [49, 50].
Viruses, however, display viral infection-associated toxicity, immunological compromise, and possible mutagenic or carcinogenic effects that make this approach potentially dangerous [1].
The prior art is deficient in methods to enhance wound healing and enhanced wound coverage materials.

Method used

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  • Methods to enhance wound healing and enhanced wound coverage material
  • Methods to enhance wound healing and enhanced wound coverage material
  • Methods to enhance wound healing and enhanced wound coverage material

Examples

Experimental program
Comparison scheme
Effect test

example 1

Experimental Animals--Rats

[0066] Adult male Sprague-Dawley rats (350-375 g) were placed in wire bottom cages and housed in a temperature-controlled room with a 12 hour light-dark cycle. The animals were acclimatized to their environment for 7 days prior to the start of the blinded study. All received equal amounts of a liquid diet of Sustacal (Mead Johnson Nutritionals, Evansville, Ind., USA) and water ad libitum throughout the study. Each rat received a 60% total body surface area (TBSA) full-thickness scald burn. Thermally injured rats were then randomly divided into:

[0067] (a) 2 groups to receive injections of cholesterol-containing cationic liposomes (20 .mu.l liposomes in 180 .mu.l saline, n=28), or saline (control, 200 .mu.l, n=28);

[0068] (b) 2 groups to receive weekly subcutaneous injections of liposomes (10 .mu.l liposomes in 180 .mu.l saline) containing 2.2 .mu.g of an IGF-I cDNA construct and 0.2 .mu.g of the reporter gene .beta.-galactosidase, Lac Z cDNA construct driven ...

example 2

Experimental Animals--Pigs

[0070] The wound repair mechanisms in Yorkshire mini-pigs are closest to the same mechanisms in humans. Thus, Yorkshire mini-pigs are a well-described model and have been used in several experimental trauma studies. Each of 10 Yorkshire swines receive 4 full-thickness wounds (standard model) under anesthesia and analgesia. Each wound site is square or rectangular in shape, with an approximate dimension of 8.times.8 cm, spaced approximately 5 cm between sites and confined to the area of the upper flank and back. The wounds must be positioned and placed according to a particular scheme such that the animal can lie comfortably on its side following release from the restraining hammock.

[0071] Immediately after wound induction, the wound is covered with human fetal chorion / amnion, INTEGRA.TM. (Life Science), ALLODERM.TM. (Life-Cell) or BIOBRANE.TM. (Dow-Hickhan). The cover is stapled to the unburned wound and covered with triple-antibiotic ointment-impregnated g...

example 3

Liposomes

[0073] The liposomes used were cholesterol-containing cationic liposomes, DMRIE-C Reagent (1,2-dimyristyloxypropyl-3-dimethyl-hydroxyl ethyl ammonium bromide) prepared with cholesterol membrane-filtered water (Life Technologies, Rockville, Md.). The IGF-I cDNA construct (FIG. 2) consisted of a cytomegalovirus driven IGF-I cDNA plasmid prepared at the UTMB Sealy Center for Molecular Science Recombinant DNA Core Facility (the IGF-I cDNA was a kind gift of G. Rotwein, NIH, Bethesda, Md.). The doses used were 10% liposomes (the highest concentration used in DNA transfer experiments that does not have deleterious consequences on DNA solubility and is compatible with gene transfer paradigms). In order to determine the time course of liposomal effects, liposomes were injected intravenously into the tail vein of rats in group (a) 0.5 h after the thermal injury and changes were examined over a 7-day period. The volume of 200 .mu.l is an amount that can be administered into the tail ...

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Abstract

The present invention describes the incorporation of liposomal gene constructs directly into a wound to further improve wound repair, or into wound coverage and / or closure materials to enhance the functionality of the material. The present invention further describes the use of human fetal membranes (e.g., amnion) enhanced with the liposomal gene therapy as a wound coverage material in full-thickness wound repair. The enhanced fetal membranes or enhanced cadaver skin have advantages over currently used materials lacking the liposomal gene construct and are an efficient and safe approach to improve clinical outcome in patients with burn injuries.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001] This is a divisional application of U.S. Ser. No. 09 / 602,183, filed on Jun. 22, 2000, which claims benefit of priority of provisional application U.S. Serial No. 60 / 140,196, filed Jun. 22, 1999, now abandoned.BACKGROUND OF THE INVENTION[0002] 1. Field of the Invention[0003] The present invention relates generally to the field of trauma medicine and wounds. More specifically the present invention relates to methods of enhancing wound healing and enhanced wound coverage materials.[0004] 2. Description of the Related Art[0005] Burn injuries represent one of the most severe forms of trauma. The larger the burn injury, the more severe the consequences and the higher the chance of poor extended outcomes and death. There are over 2 million burn patients annually, and costs for treatment exceed one billion dollars a year. Fire and burn injuries are the third leading cause of injuries and death in children aged 1 to 18 years. The number of mortal...

Claims

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Application Information

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IPC IPC(8): A61F13/00A61K9/127A61K38/00A61K38/18A61K38/22A61K38/27A61K38/28A61K38/30A61K47/28A61K48/00A61L15/00A61L15/32A61L15/40A61L15/44A61L26/00A61P17/02A61P41/00A61P43/00
CPCA61K9/1272A61K38/30A61K48/00A61L15/32A61L15/40A61L26/0047A61P17/02A61P41/00A61P43/00
Inventor HERNDON, DAVID N.PEREZ-POLO, JOSE R.BARROW, ROBERT E.
Owner RES DEVMENT FOUND
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