Patent Application
20150359926
1. Field of the Invention
The present invention relates to the field of biomaterials and supportive devices for medical applications. More specifically, the present invention relates to compositions and production methods of proteinaceous materials, including foam dressings, foam sponges and biomaterial devices.
2. Background of the Invention
Biomaterials are commonly used in the treatment and maintenance of acute and chronic wounds of the body as well as for tissue implants, sealants and barriers. Hence, materials such as collagen and gelatin have been utilized as biocompatible materials to aid in the establishment and maintenance of a favorable environment for tissue growth and repair. On a therapeutic level, these materials generally improve fluid homeostasis and provide biocompatible matrices for tissue growth and migration. On a physical level, they serve as a secondary covering to protect and limit access to the wound from the external environment. The present invention discloses the construction and utilization of inert and bioactive peptides and proteins to produce medical articles in the form of solidified foams, pads, and granular or multiparticulate constructs for application within or upon bodily tissues. In addition to the benefits of traditional materials, the present compositions and methods, through the passive release of bioactive molecules and substances as well as the option of delivery of beneficial pharmaceutical agents, display the added benefit of altering the local environment within the wound in such a manner to be conducive to tissue growth while inhibiting opportunistic microorganisms generally detrimental medical health.
Similar devices in the prior art comprised of gelatin and collagen have disadvantages depending on their specific embodiment, including (a) lacking, or limited, control of microorganisms, (b) lower biocompatibility, (c) higher toxicity and (d) if bovine sourced, the possibility of transferring Creutzfelt-Jacob disease (vCJD).
Consequently, a need has been demonstrated for the invention which provides compositions and methods for biocompatible biomaterials with at least one of the following: (a) improved control of microorganisms, (b) improved biocompatibility, (c) lower toxicity, and (d) no vCJD potential.
A search of the prior art did not disclose any patents that read directly on the claims of the instant invention; however, the following references were considered related.
The purpose of the invention is to provide compositions and methods for biocompatible biomaterials with at least one of the following advantages over the prior art: (a) improved control of microorganisms, (b) improved biocompatibility, (c) lower toxicity, and (d) no vCJD potential. These combined benefits cascade to provide improved efficacy, improved patient compliance and improved performance, while limiting clinical complications in treatment.
In one embodiment of the invention, a bioactive protein and adjunct additives are processed to exact a suspension containing gaseous inclusions or bubbles. The gaseous inclusions or bubbles may be imparted by mechanical means through vigorous agitation, homogenization and/or direct injection of gaseous products or by chemical means such as effervescent chemical or emulsification reactions. This composition is then processed in a manner to remove the liquid or fluid character and produce an article possessing a solidified structure with the rigid or semi-rigid characteristics of commonly made and used closed cell and open cell foam products. This may be achieved by the addition of energy in the form of heat or irradiation, by chemical means through the use of commonly utilized reactive cross-linking agents, and/or lyophilization. The articles may be further processed through sizing and packaged in a plurality of formats for therapeutic applications in medicine. Upon application to tissues, the system manages exudate, releases bioactive molecules beneficial to the process of healing, seals tissues, aids in the control and reduction of opportunistic bacteria, and serves as a primary cushion for wounds.
A first aspect is a proteinaceous foam composition and method of production that provides a preferred structural framework for use as foam dressings, foam sponges including hemostatic sponges, and biomaterial devices useful as tissue sealants and/or barriers. The composition and methods comprise an amino acid containing compound of natural, synthetic or recombinant origin selected from the group of proteins, glycoprotein, peptides, poly amino acids, protein hydrolysates, peptide hydrolysates, derivatives of this group and any combination thereof, and at least one augmentative polymer. Particularly useful amino acid containing compounds are albumin, gelatin and collagen. Particularly useful augmentative polymers are chitosan, glucosamine, N-acetyl glucosamine, hyaluronic acid, sulfoglucosamine, glycosylamine, and galactosamine.
In broad terms, a preferred embodiment of the composition and methods are further comprised of at least one secondary component selected from the group of an adjunct compound, an anti-infective, a crosslink augmentation agent, and a crosslinking-agent.
One advantage of the invention is that the augmentative polymer promotes the formation of the desired final physical structure, function and/or lessens toxicity, including lessening the amount of crosslinking-agent, by providing additional reactive sites than those inherent to the amino acid containing compound.
Another advantage of the invention is that the adjunct compound can promote the formation and retention of the desired final physical structure by stabilizing the liquid, preserving the composition, plasticizing the composition, and/or enhancing the viscosity.
Another advantage of the invention is that the anti-infective can limit, arrest or reduce the growth, attachment, colonization or quantity of infective micro organisms, including planktonic or biofilm phenotypes such as pathogenic and nonpathogentic bacteria, viruses, fungi, and yeasts.
Another advantage of the invention is that the crosslinking-agent can chemically react with the amino acid containing compound and secondary components to form crosslinks that provide the composition the desired final physical structure.
Another advantage of the invention is that the crosslink augmentation agent can promote the formation of the desired final physical structure, function or lessen toxicity through the potentiation of crosslinks, which lessen the total crosslinking-agent required, thereby lessening toxicity and improving biocompatibility.
Another aspect is a proteinaceous foam composition and method of production based on lactoferrin that provides a preferred structural framework for use as foam dressings, foam sponges including hemostatic sponges, and biomaterial devices useful as tissue sealants and/or barriers. The composition and methods comprise lactoferrin, or derivatives thereof, of synthetic or recombinant origin.
In broad terms, a preferred embodiment of the composition and methods are further comprised of at least one secondary component selected from the group of an augmentative polymer, an adjunct compound, an anti-infective, a crosslink augmentation agent, and a crosslinking-agent.
One advantage of the invention is that the augmentative polymer promotes the formation of the desired final physical structure, function and/or lessens toxicity, including lessening the amount of crosslinking-agent, by providing additional reactive sites than those inherent to the amino acid containing compound.
Another advantage of the invention is that the adjunct compound can promote the formation and retention of the desired final physical structure by stabilizing the liquid, preserving the composition, plasticizing the composition, and/or enhancing the viscosity.
Another advantage of the invention is that the anti-infective can limit, arrest or reduce the growth, attachment, colonization or quantity of infective micro organisms, including planktonic or biofilm phenotypes such as pathogenic and nonpathogentic bacteria, viruses, fungi, and yeasts.
Another advantage of the invention is that the crosslinking-agent can chemically react with the amino acid containing compound and secondary components to form crosslinks that provide the composition the desired final physical structure.
Another advantage of the invention is that the crosslink augmentation agent can promote the formation of the desired final physical structure, function or lessen toxicity through the potentiation of crosslinks, which lessen the total crosslinking-agent required, thereby lessening toxicity and improving biocompatibility.
In another embodiment of the invention, a bioactive protein and adjunct additives are processed to produce multiparticulates. The multiparticulates may be imparted by physical means through emulsification or homogenization followed by crosslinking to form a suspension, extrusion and spray drying, depending on the desire final structure. Upon application to tissues, the system manages exudate, releases bioactive molecules, and aids in the control and reduction of opportunistic bacteria.
A first aspect is a proteinaceous multiparticulate composition and methods of production that provide a preferred structural framework for use as multiparticulate biomaterial devices. The composition and methods comprise an amino acid containing compound of natural, synthetic or recombinant origin selected from the group of proteins, glycoprotein, peptides, poly amino acids, protein hydrolysates, peptide hydrolysates, derivatives of this group and any combination thereof, and at least one augmentative polymer. Particularly useful amino acid containing compounds are albumin, gelatin and collagen. Particularly useful augmentative polymers are chitosan, glucosamine, N-acetyl glucosamine, hyaluronic acid, sulfoglucosamine, glycosylamine, and galactosamine.
In broad terms, a preferred embodiment of the composition and methods are further comprised of at least one secondary component selected from the group of an adjunct compound, an anti-infective, a crosslink augmentation agent, and a crosslinking-agent.
One advantage of the invention is that the augmentative polymer promotes the formation of the desired final physical structure, function and/or lessens toxicity, including lessening the amount of crosslinking-agent, by providing additional reactive sites than those inherent to the amino acid containing compound.
Another advantage of the invention is that the adjunct compound can promote the formation and retention of the desired final physical structure by stabilizing the liquid, preserving the composition, plasticizing the composition, and/or enhancing the viscosity.
Another advantage of the invention is that the anti-infective can limit, arrest or reduce the growth, attachment, colonization or quantity of infective micro organisms, including planktonic or biofilm phenotypes such as pathogenic and nonpathogentic bacteria, viruses, fungi, and yeasts.
Another advantage of the invention is that the crosslinking-agent can chemically react with the amino acid containing compound and secondary components to form crosslinks that provide the composition the desired final physical structure.
Another advantage of the invention is that the crosslink augmentation agent can promote the formation of the desired final physical structure, function or lessen toxicity through the potentiation of crosslinks, which lessen the total crosslinking-agent required, thereby lessening toxicity and improving biocompatibility.
Another aspect is a proteinaceous multiparticulate composition and methods of production based on lactoferrin that provide a preferred structural framework for use as multiparticulate biomaterial devices. The composition and methods comprise lactoferrin, or derivatives thereof, of synthetic or recombinant origin.
In broad terms, a preferred embodiment of the composition and methods are further comprised of at least one secondary component selected from the group of an augmentative polymer, an adjunct compound, an anti-infective, a crosslink augmentation agent, and a crosslinking-agent.
One advantage of the invention is that the augmentative polymer promotes the formation of the desired final physical structure, function and/or lessens toxicity, including lessening the amount of crosslinking-agent, by providing additional reactive sites than those inherent to the amino acid containing compound.
Another advantage of the invention is that the adjunct compound can promote the formation and retention of the desired final physical structure by stabilizing the liquid, preserving the composition, plasticizing the composition, and/or enhancing the viscosity.
Another advantage of the invention is that the anti-infective can limit, arrest or reduce the growth, attachment, colonization or quantity of infective micro organisms, including planktonic or biofilm phenotypes such as pathogenic and nonpathogentic bacteria, viruses, fungi, and yeasts.
Another advantage of the invention is that the crosslinking-agent can chemically react with the amino acid containing compound and secondary components to form crosslinks that provide the composition the desired final physical structure.
Another advantage of the invention is that the crosslink augmentation agent can promote the formation of the desired final physical structure, function or lessen toxicity through the potentiation of crosslinks, which lessen the total crosslinking-agent required, thereby lessening toxicity and improving biocompatibility.
Further aspects will become apparent from consideration of the ensuing description of preferred embodiments of the invention. A person skilled in the art will realize that other embodiments of the invention are possible and that the details of the invention can be modified in a number of respects, all without departing from the inventive concept. Thus, the following drawings and description are to be regarded as illustrative in nature and not restrictive.
There are no drawings.
DEFINITIONS: As used in this description and the accompanying claims, the following terms shall have the meanings indicated, unless the context otherwise requires:
“Proteinaceous” as broadly defined and used herein, means an amino acid containing compound or composition selected from the group of proteins, peptides, poly amino acids, protein hydrolysates, peptide hydrolysates, derivatives of this group or any combination thereof.
“Crosslinking-agent” as broadly defined and used herein, means any reagent that produces a chemical reaction that forms crosslinks of proteinaceous compounds.
“Augmentative polymer” as broadly defined and used herein, means any polymer when part of a proteinaceous composition as disclosed herein, that potentiates the formation of the desired final physical structure, function or toxicity, including lessening the amount of crosslinking-agent required or residual crosslinking-agent.
“Adjunctive compound” as broadly defined and used herein, means any compound when part of a proteinaceous composition as disclosed herein, that potentiates the formation and retention of the desired final physical structure, including lessening the amount of crosslinking-agent required or residual crosslinking-agent, as a stabilizer, preservative, plasticizer or viscosity enhancer.
“Crosslink augmentation agent” as broadly defined and used herein, means any compound when part of a proteinaceous composition as disclosed herein, that potentiates the formation of the desired final physical structure, function or toxicity through the potentiation of crosslinks, including lessening the amount of crosslinking-agent required or residual crosslinking-agent.
“Foam” as broadly defined and used herein, means a material formed by trapping gas bubbles within for form cells. Foam further includes two types of distinct structure, open and closed cell types. By example, open cell foams contain primarily open pores that are interconnected and most commonly formed by the rupture of the cells during process. Open cell foams are therefore porous. By example, closed cell foams do not have interconnected pores, as the cells formed during processing are largely intact and unruptured.
“Anti-infective” when used as an adjective or adverb herein, means broadly having or exhibiting the ability to limit, arrest or reduce the growth, attachment, colonization or quantity of infective micro organisms, including planktonic or biofilm phenotypes such as pathogenic and nonpathogentic bacteria, viruses, fungi, and yeasts. When used as a noun herein, or as a noun derivative, the noun means any substance or composition having or exhibiting the ability to limit, arrest or reduce the growth, attachment, colonization or quantity of infective micro organisms, including planktonic or biofilm phenotypes such as pathogenic and nonpathogentic bacteria, viruses, fungi, and yeasts.
“Primary Dressing” when used herein shall mean any foreign material, any collection of foreign materials, or any composition of foreign materials positioned in direct contact with a wound bed. Examples include a primary dressing separating the tissue bed from a secondary dressing.
“Secondary Dressing” when used herein shall mean any foreign material, collection of foreign materials or any composition of foreign materials positioned on top of a primary dressing. Examples include wraps, tapes or dressings used to hold a primary dressing in place.
Broadly a proteinaceous foam composition is disclosed which provides preferred structural framework for use as foam dressings, foam sponges including hemostatic sponges, and biomaterial devices useful as tissue sealants and/or barriers.
The composition comprises an amino acid containing compound of natural, synthetic or recombinant origin selected from the group of proteins, glycoprotein, peptides, poly amino acids, protein hydrolysates, peptide hydrolysates, derivatives of this group and any combination thereof, and at least one augmentative polymer. Particularly useful amino acid containing compounds are albumin, gelatin and collagen. Particularly useful concentrations range from 2.5 to 25%. Particularly useful augmentative polymers are chitosan, glucosamine, N-acetyl glucosamine, hyaluronic acid, sulfoglucosamine, glycosylamine, and galactosamine. Particularly useful concentrations range from 0.001 to 20%.
A second best mode of the invention further comprises at least one adjunct compound to promote the formation and retention of the desired final physical structure, including lessening the amount of crosslinking-agent required or remaining (less toxicity). Useful adjunct compounds are stabilizers, preservatives, plasticizers, viscosity enhancers, and any combination thereof. Particularly useful adjunct compounds are surfactants, fatty acids, hydrogen peroxide, and poly(ethylene glycol).
A third best mode of the invention further comprises at least one anti-infective to reduce the growth, attachment, colonization or quantity of infective micro organisms, including planktonic or biofilm phenotypes of pathogenic and nonpathogentic bacteria, viruses, fungi, and yeasts. Particularly useful anti-infectives are urea, fatty acids, silver compounds, lysozyme, sugar alcohols, methylene blue, gentian violet, glycopeptides, and lipoglycopeptides.
A fourth best mode of the invention further comprises at least one crosslinking-agent to produce a chemical reaction which chemically crosslinks compounds in the composition that contain reactive sites together to form the solidified structure. Particularly useful crosslinking-agents are formaldehyde, glutaraldehyde, acetaldehyde, malonaldehyde, succinaldehyde, adipaldehyde, and dialdehyde starch. Particularly useful concentrations range from 0.001 to 10% (unreacted).
A fifth best mode of the invention further comprises at least one crosslink augmentation agent to promote the formation of the desired final physical structure, function or toxicity through the potentiation of crosslinks, including lessening the amount of crosslinking-agent required or remaining (toxicity). Particularly useful crosslink augmentation agents are polyamine compounds, resorcinol, vanillin, urea, nicotinamide, carbodiimide, and cyanamide.
One method of the invention may be operated by combining a gas with an amino acid containing compound, an augmentative polymer and at least one secondary component selected from the group of: (i) an adjunct compound, (ii) an anti-infective, (iii) a crosslink augmentation agent, and (iv) a crosslinking-agent.
The embodiments are further described by the following aspects:
Broadly a lactoferrin based foam composition is disclosed which provides preferred structural framework and anti-infective properties for use as foam dressings, foam sponges including hemostatic sponges, and biomaterial devices useful as tissue sealants and/or barriers.
The composition comprises lactoferrin, or derivatives thereof including lactoferricin, from natural, synthetic or recombinant origin in a solidified cellular foam structure. Particularly useful concentrations range from 2.5 to 25%.
A second best mode of the invention further comprises at least one augmentative polymer. Particularly useful augmentative polymers are chitosan, glucosamine, N-acetyl glucosamine, hyaluronic acid, sulfoglucosamine, glycosylamine, and galactosamine. Particularly useful concentrations range from 0.001 to 20%.
A third best mode of the invention further comprises at least one adjunct compound to promote the formation and retention of the desired final physical structure, including lessening the amount of crosslinking-agent required or remaining (less toxicity). Useful adjunct compounds are stabilizers, preservatives, plasticizers, viscosity enhancers, and any combination thereof. Particularly useful adjunct compounds are surfactants, fatty acids, hydrogen peroxide, and poly(ethylene glycol).
A fourth best mode of the invention further comprises at least one anti-infective to reduce the growth, attachment, colonization or quantity of infective micro organisms, including planktonic or biofilm phenotypes of pathogenic and nonpathogentic bacteria, viruses, fungi, and yeasts. Particularly useful anti-infectives are urea, fatty acids, silver compounds, lysozyme, sugar alcohols, methylene blue, gentian violet, glycopeptides, and lipoglycopeptides.
A fifth best mode of the invention further comprises at least one crosslinking-agent to produce a chemical reaction which chemically crosslinks compounds in the composition that contain reactive sites together to form the solidified cellular foam structure. Particularly useful crosslinking-agents are formaldehyde, glutaraldehyde, acetaldehyde, malonaldehyde, succinaldehyde, adipaldehyde, and dialdehyde starch. Particularly useful concentrations range from 0.001 to 10%. As known throughout the art, modification of any active protein often results in a severe diminishment, or total loss of activity. In fact, lactoferrin produced recombinantly, still maintains >90% similarity and yet is known to lose antimicrobial activity even from such a relatively small change. A priori, it was expected that crosslinking would likewise terminate the antimicrobial activity of lactoferrin, as the crosslinking process effectively denatures it, which is also known to terminate antimicrobial efficacy. However, upon testing the resulting crosslinked materials, a very significant antimicrobial effect was unexpectedly discovered, even surpassing the native lactoferrin activity for some microbes.
A sixth best mode of the invention further comprises at least one crosslink augmentation agent to promote the formation of the desired final physical structure, function or toxicity through the potentiation of crosslinks, including lessening the amount of crosslinking-agent required or remaining (toxicity). Particularly useful crosslink augmentation agents are polyamine compounds, resorcinol, vanillin, urea, nicotinamide, carbodiimide, and cyanamide.
The final product may include crosslinks with lactoferrin alone, or crosslinks with lactoferrin and any other component of the composition with reactive sites for the crosslinking agent. In fact, this is desirable when the composition includes augmentative polymers and crosslink augmentation agents to impact the physical properties of the solidified product in use.
One method of the invention may be operated by combining a gas with lactoferrin, and at least one secondary component selected from the group of: (i) an augmentative polymer, (ii) an adjunct compound, (iii) an anti-infective, (iv) a crosslink augmentation agent, and (v) a crosslinking-agent.
The embodiments are further described by the following aspects:
Broadly a multiparticulate composition is disclosed which provides a preferred structural framework for useful as biomaterial devices, tissue implants and tissue dressings including wound dressings.
The composition comprises an amino acid containing compound of natural, synthetic or recombinant origin selected from the group of proteins, glycoprotein, peptides, poly amino acids, protein hydrolysates, peptide hydrolysates, derivatives of this group and any combination thereof, and at least one augmentative polymer in a multiparticulate structure. Particularly useful amino acid containing compounds are albumin, gelatin and collagen. Particularly useful augmentative polymers are chitosan, glucosamine, N-acetyl glucosamine, hyaluronic acid, sulfoglucosamine, glycosylamine, and galactosamine.
A second best mode of the invention further comprises at least one adjunct compound to promote the formation and retention of the desired final physical structure, including lessening the amount of crosslinking-agent required or remaining (less toxicity). Useful adjunct compounds are stabilizers, preservatives, plasticizers, viscosity enhancers, and any combination thereof. Particularly useful adjunct compounds are surfactants, fatty acids, hydrogen peroxide, and poly(ethylene glycol).
A third best mode of the invention further comprises at least one anti-infective to reduce the growth, attachment, colonization or quantity of infective micro organisms, including planktonic or biofilm phenotypes of pathogenic and nonpathogentic bacteria, viruses, fungi, and yeasts. Particularly useful anti-infectives are urea, fatty acids, silver compounds, lysozyme, sugar alcohols, methylene blue, gentian violet, glycopeptides, and lipoglycopeptides.
A fourth best mode of the invention further comprises at least one crosslinking-agent to produce a chemical reaction which chemically crosslinks compounds in the composition that contain reactive sites together into a solidified structure. Particularly useful crosslinking-agents are formaldehyde, glutaraldehyde, acetaldehyde, malonaldehyde, succinaldehyde, adipaldehyde, and dialdehyde starch.
A fifth best mode of the invention further comprises at least one crosslink augmentation agent to promote the formation of the desired final physical structure, function or toxicity through the potentiation of crosslinks, including lessening the amount of crosslinking-agent required or remaining (toxicity). Particularly useful crosslink augmentation agents are polyamine compounds, resorcinol, vanillin, urea, nicotinamide, carbodiimide, and cyanamide.
One method of the invention may be operated by combining an amino acid containing compound, an augmentative polymer and at least one secondary component selected from the group of: (i) an adjunct compound, (ii) an anti-infective, (iii) a crosslink augmentation agent, and (iv) a crosslinking-agent.
The embodiments are further described by the following aspects:
Broadly a multiparticulate composition is disclosed which provides a preferred structural framework for useful as biomaterial devices, tissue implants and tissue dressings including wound dressings.
The composition comprises lactoferrin, or derivatives thereof including lactoferricin, from natural, synthetic or recombinant origin in a solidified multiparticulate structure.
A second best mode of the invention further comprises at least one augmentative polymer. Particularly useful augmentative polymers are chitosan, glucosamine, N-acetyl glucosamine, hyaluronic acid, sulfoglucosamine, glycosylamine, and galactosamine.
A third best mode of the invention further comprises at least one adjunct compound to promote the formation and retention of the desired final physical structure, including lessening the amount of crosslinking-agent required or remaining (less toxicity). Useful adjunct compounds are stabilizers, preservatives, plasticizers, viscosity enhancers, and any combination thereof. Particularly useful adjunct compounds are surfactants, fatty acids, hydrogen peroxide, and poly(ethylene glycol).
A fourth best mode of the invention further comprises at least one anti-infective to reduce the growth, attachment, colonization or quantity of infective micro organisms, including planktonic or biofilm phenotypes of pathogenic and nonpathogentic bacteria, viruses, fungi, and yeasts. Particularly useful anti-infectives are urea, fatty acids, silver compounds, lysozyme, sugar alcohols, methylene blue, gentian violet, glycopeptides, and lipoglycopeptides.
A fifth best mode of the invention further comprises at least one crosslinking-agent to produce a chemical reaction which chemically crosslinks compounds within the composition that contain reactive sites together into a solidified structure. Particularly useful crosslinking-agents are formaldehyde, glutaraldehyde, acetaldehyde, malonaldehyde, succinaldehyde, adipaldehyde, and dialdehyde starch.
A sixth best mode of the invention further comprises at least one crosslink augmentation agent to promote the formation of the desired final physical structure, function or toxicity through the potentiation of crosslinks, including lessening the amount of crosslinking-agent required or remaining (toxicity). Particularly useful crosslink augmentation agents are polyamine compounds, resorcinol, vanillin, urea, nicotinamide, carbodiimide, and cyanamide.
One method of the invention may be operated by combining lactoferrin, and at least one secondary component selected from the group of: (i) an augmentative polymer, (ii) an adjunct compound, (iii) an anti-infective, (iv) a crosslink augmentation agent, and (v) a crosslinking-agent.
The embodiments are further described by the following aspects:
Embodiments disclosed above are further described by the following aspects:
Embodiments disclosed above are further described by the following aspects:
To produce open-cell foam, perform the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam, perform the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam, perform the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam, perform the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam perform, the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam perform, the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam perform, the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam perform, the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam perform, the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
Closed-cell foam method
To produce open-cell foam perform, the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam perform, the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam perform, the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam perform, the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
To produce open-cell foam perform, the above method followed by freezing of the foam material at −20° C. Lyophilize the foam until dry.
Note: Aldehyde may be increased to make more firm or reduced to decrease toxicity as required by scale.
Note: Aldehyde may be increased to make more firm or reduced to decrease toxicity as required by scale.
Note: Aldehyde may be increased to make more firm or reduced to decrease toxicity as required by scale.
