A porous polyurethane dermal scaffold and a method of making the same

Abstract

This invention relates to the field of skin tissue repair material manufacturing, and particularly to a porous polyurethane dermal scaffold and its preparation method. The preparation method of the porous polyurethane dermal scaffold includes the following steps: adding dibutyltin dilaurate, triethylenediamine, butanediol, and silicone oil sequentially to polyethylene glycol and mixing thoroughly to obtain a mixed solution; adding lysine diisocyanate and ultrapure water to the mixed solution and mixing thoroughly to obtain a mixture; placing the mixture in a mold and allowing it to foam and solidify, then curing, demolding, washing, and drying to obtain the porous polyurethane dermal scaffold. The preparation method of this invention is simple, the material has a pore size of 30-200 μm, a porosity > 95%, a tensile strength of 10-12 N / cm, an elongation at break > 50%, is non-toxic and non-immunogenic, and meets the biocompatibility requirements of standards such as GB / T 16886, showing great application potential in wound dressings and skin tissue engineering.

Description

Technical Field

[0001] This invention relates to the field of skin tissue repair material manufacturing, and in particular to a porous polyurethane dermal scaffold and its preparation method. Background Technology

[0002] Artificial dermis, developed by Yannas and Burkel in 1980, is a bioactive, temporary scaffold material and absorbable dressing that allows for the growth and migration of autologous cells. Initially used to treat burn wounds, it has been widely adopted as a biomaterial-synthesized dermal substitute for various wound repairs. It offers advantages such as reduced need for donor tissue, reduced wound contraction, rapid coverage of large, acute wounds, minimal immune rejection, low surgical risk, simple operation, significantly improved appearance and function after healing, and strong wound repair capabilities. These advantages overcome the significant drawbacks of traditional repair methods like flaps and skin grafts, including large-scale damage, high surgical risk, and insufficient scar contraction.

[0003] With the improvement of people's living standards, the requirements for wound treatment are also increasing. The development and popularization of artificial dermis will completely change the high dependence of wound repair on autologous skin sources, improving the success rate and quality of wound repair. Existing artificial dermis materials, whether Integra, MatriDerm, Pelanac, or Lando, and whether derived from porcine or bovine tissue, cannot completely replace the characteristics of natural skin, and have fundamental problems such as susceptibility to infection or the need for secondary dermal transplantation. The optimal artificial dermis should simultaneously meet the following characteristics: 1. Antibacterial function; 2. Good permeability; 3. Good controllable biodegradability; 4. Low toxicity and good immunogenicity; 5. Easy structural maintenance.

[0004] Polyurethane, as a novel organic polymer material, possesses excellent biocompatibility, thus showing promising application prospects as a biomedical material. Furthermore, polyurethane can be artificially synthesized, its structure and morphology are controllable, and its cost is relatively low, making it a promising candidate for wound dressings and skin tissue engineering. However, existing polyurethane artificial dermis materials suffer from the following technical problems: First, the safety of existing polyurethane degradation products is insufficient; aromatic isocyanate degradation products have potential toxicity, and aliphatic polyurethane degradation processes easily induce local inflammation. Second, the porous structure makes it difficult to balance permeability and mechanical properties; uneven pore size distribution, porosity, and connectivity are difficult to control, and the foaming height and shape are difficult to precisely control. Third, it lacks effective antibacterial function; the scaffold structure has poor maintainability and is susceptible to infection or collapse and deformation. Fourth, the polyurethane foaming process has poor controllability; improper proportions of catalysts, foaming agents, and silicone oils can easily lead to foaming failure, brittle foam, or unsuitable hardness, resulting in a low product qualification rate. Summary of the Invention

[0005] Based on the above, this invention provides a porous polyurethane dermal scaffold and its preparation method. The porous polyurethane dermal scaffold with good softness and elasticity is obtained by catalyzing a lysine diisocyanate and polyethylene glycol system with triethylenediamine and dibutyltin dilaurate, adding butanediol for chain extension, and adding ultrapure water for foaming.

[0006] To achieve the above objectives, the present invention provides the following solution: One of the technical solutions of this invention is a method for preparing a porous polyurethane dermal scaffold, comprising the following steps: Dibutyltin dilaurate, triethylenediamine, butanediol and silicone oil were added sequentially to polyethylene glycol and mixed thoroughly to obtain a mixed solution. Lysine diisocyanate and ultrapure water were added to the mixed solution and mixed thoroughly to obtain a mixture; The mixture is placed in a mold and allowed to stand to foam and form. After curing, it is demolded, cleaned, and dried to obtain the porous polyurethane leather support.

[0007] The second technical solution of the present invention is a porous polyurethane dermal scaffold prepared by the above-mentioned preparation method.

[0008] Compared with the prior art, the present invention has the following beneficial effects: ① Lysine diisocyanate and polyethylene glycol are both biocompatible and safe raw materials. The porous polyurethane dermal scaffold prepared from them is non-immunotoxic and degradable. The degradation product is lysine (an essential amino acid for the human body), and the degradation product does not lower the pH value of nearby tissues or cause inflammation.

[0009] ②The porous polyurethane dermal scaffold of the present invention has a porous structure suitable for cell and tissue permeation, promotes angiogenesis, fibroblast and collagen deposition, and accelerates skin tissue repair.

[0010] ③ The polyurethane leather support of the present invention is easy to maintain and the macroscopic foaming height and shape of the leather support can be adjusted according to the mold to achieve personalized customization. Attached Figure Description

[0011] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0012] Figure 1 This is a macroscopic view of the polyurethane dermal scaffold prepared in Example 1.

[0013] Figure 2 The image shows a microscopic scanning electron microscope (SEM) image of the polyurethane dermal scaffold prepared in Example 1.

[0014] Figure 3 The figure shows the MTT cytotoxicity test results of the polyurethane dermal scaffold prepared in Example 1. Detailed Implementation

[0015] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0016] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0017] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0018] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0019] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0020] Currently, polyurethanes used in the medical field can be divided into biodegradable and non-biodegradable polyurethanes. Biodegradable polyurethanes are synthesized from aliphatic diisocyanates as hard segments and polyethers and polyols as soft segments, and can be broken down into small molecules that can be absorbed and metabolized by the body. Non-biodegradable polyurethanes are mainly synthesized from aromatic diisocyanates and can be used as long-term implants in the human body. Therefore, polyurethanes can be used for both permanent medical implants and systems that require degradation, such as tissue regeneration scaffolds. Improving the "hard segments" and "soft segments" of polyurethanes, or blending them with natural materials to prepare artificial skin with better biocompatibility, is a developing trend.

[0021] The first aspect of this invention provides a method for preparing a porous polyurethane dermal scaffold, comprising the following steps: Dibutyltin dilaurate, triethylenediamine, butanediol and silicone oil were added sequentially to polyethylene glycol and mixed thoroughly to obtain a mixed solution. Lysine diisocyanate and ultrapure water were added to the mixed solution and mixed thoroughly to obtain a mixture; The mixture is placed in a mold and allowed to stand to foam and form. After curing, it is demolded, cleaned, and dried to obtain the porous polyurethane leather support.

[0022] In a preferred embodiment of the present invention, the mass ratio of the lysine diisocyanate to the polyethylene glycol, butanediol, dibutyltin dilaurate, triethylenediamine, silicone oil and ultrapure water is (45-50):(50-55):(1.2-1.25):(0.1-0.2):(0.15-0.3):(2.3-2.5):1.

[0023] In this invention, silicone oil, as a surfactant, mainly plays the role of reducing the surface tension of the system, promoting the uniform distribution of bubbles, and preventing foam collapse.

[0024] In a preferred embodiment of the present invention, before adding dibutyltin dilaurate, triethylenediamine, butanediol and silicone oil to polyethylene glycol in sequence and mixing them evenly, the method further includes a step of stirring polyethylene glycol for 0.25-0.75 hours.

[0025] The purpose of stirring involved in this invention is to achieve uniform mixing. No special limit is placed on the stirring speed; stirring speeds commonly used by those skilled in the art can be adopted.

[0026] In a preferred embodiment of the present invention, dibutyltin dilaurate, triethylenediamine, butanediol and silicone oil are added to polyethylene glycol in sequence and mixed evenly by stirring for 0.5-1 h.

[0027] In a preferred embodiment of the present invention, the lysine diisocyanate and ultrapure water are added to the mixed solution and stirred for 2-5 minutes.

[0028] In a preferred embodiment of the present invention, the temperature for static foaming molding is 55-60°C, and the time for static foaming molding is 1-5 minutes.

[0029] In a preferred embodiment of the present invention, the curing temperature is 55-60°C and the curing time is 2-3 hours.

[0030] In a preferred embodiment of the present invention, the drying temperature is 80-100℃ and the drying time is 3-5 hours.

[0031] A second aspect of the present invention provides a porous polyurethane dermal scaffold prepared using the above-described preparation method.

[0032] In this invention, lysine diisocyanate and polyethylene glycol are the hard and soft segments, respectively, and are synthesized in one step using triethylenediamine and dibutyltin dilaurate as a double crosslinking agent to obtain a porous polyurethane dermal scaffold with good softness and elasticity. The preparation method of this invention is simple, the material has a pore size of 30-200 μm, a porosity >95%, a tensile strength of 10-12 N / cm, an elongation at break >50%, is non-toxic and non-immunogenic, and meets the biocompatibility requirements of standards such as GB / T 16886. It has great application potential in wound dressings and skin tissue engineering.

[0033] Unless otherwise specified, the technical solutions described in this invention are all conventional solutions in the field, and the reagents or raw materials used are all purchased from commercial channels or are publicly available unless otherwise specified.

[0034] The lysine diisocyanate used in this embodiment of the invention was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., with a purity of 95%; polyethylene glycol was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., with an average molecular weight of 400; butanediol was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., with a purity ≥98%; triethylenediamine was purchased from Shanghai Maclean Biochemical Technology Co., Ltd., with a purity of 98%; dibutyltin dilaurate was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., with a purity ≥95%; and silicone oil was purchased from Xuzhou Yihuiyang New Materials Co., Ltd., specification 8805.

[0035] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0036] Example 1 This embodiment provides a porous polyurethane dermal scaffold, which, by weight, is composed of the following raw materials: 48 parts lysine diisocyanate, 53 parts polyethylene glycol, 1.2 parts butylene glycol, 0.16 parts dibutyltin dilaurate, 0.24 parts triethylenediamine, 2.3 parts silicone oil, and 1 part ultrapure water.

[0037] The preparation method of the above-mentioned porous polyurethane dermal scaffold includes the following steps: According to the above-mentioned weight proportions, polyethylene glycol was stirred for 0.75 h; then, under stirring conditions, dibutyltin dilaurate, triethylenediamine, butanediol, and silicone oil were added slowly in sequence. After the addition was completed, stirring was continued for 0.75 h to ensure thorough mixing and obtain a mixed solution; lysine diisocyanate and ultrapure water were added to the above mixed solution under rapid stirring and stirring was continued for 3 min; the stirred mixture was poured into a clean mold, quickly transferred to a 55°C environment for standing foaming and molding for 3 min and then cured for 2.5 h; the cured sample was cooled, demolded, and washed with ultrapure water, then transferred to a 100°C oven to dry for 5 h, and after natural cooling, a polyurethane dermal support with a porous structure was obtained.

[0038] Figure 1 This is a macroscopic view of the polyurethane dermal scaffold prepared in Example 1.

[0039] Figure 2 This is a scanning electron microscope (SEM) image of the polyurethane dermal scaffold prepared in Example 1. Figure 2 As can be seen, the polyurethane dermal scaffold prepared in Example 1 has a continuous porous structure (SEM shows 20-300um), which facilitates cell and blood vessel ingrowth and has good permeability.

[0040] Figure 3 The image shows the cytotoxicity test results of the polyurethane dermal scaffold prepared in Example 1. The cytotoxicity test method was the MTT assay, and the cells used were L929 mouse fibroblasts. Figure 3 It can be seen that the polyurethane dermal scaffold of the present invention is non-cytotoxic.

[0041] The polyurethane material used in this invention to prepare the polyurethane dermal scaffold is an organic polymer material that has undergone drying treatment, eliminating the moisture and nutrients required for bacterial growth and thus possessing natural antibacterial properties.

[0042] Example 2 This embodiment provides a porous polyurethane dermal scaffold, which, by weight, is composed of the following raw materials: 50 parts lysine diisocyanate, 55 parts polyethylene glycol, 1.25 parts butylene glycol, 0.2 parts dibutyltin dilaurate, 0.3 parts triethylenediamine, 2.5 parts silicone oil, and 1 part ultrapure water.

[0043] A method for preparing a porous polyurethane dermal scaffold includes the following specific steps: The preparation method of the above-mentioned porous polyurethane dermal scaffold includes the following steps: According to the above-mentioned weight proportions, polyethylene glycol was stirred for 0.25 h; then, under stirring conditions, dibutyltin dilaurate, triethylenediamine, butanediol, and silicone oil were added slowly in sequence. After the addition was completed, stirring was continued for 1 h to ensure thorough mixing and obtain a mixed solution; lysine diisocyanate and ultrapure water were added to the above mixed solution under rapid stirring and stirring was continued for 5 min; the stirred mixture was poured into a clean mold, quickly transferred to a 60°C environment for standing foaming and molding for 1 min and then cured for 3 h; the cured sample was cooled, demolded, and washed with ultrapure water, then transferred to an 80°C oven to dry for 3 h, and after natural cooling, a polyurethane dermal support with a porous structure was obtained.

[0044] Example 3 This embodiment provides a porous polyurethane dermal scaffold, which, by weight, is composed of the following raw materials: 45 parts lysine diisocyanate, 50 parts polyethylene glycol, 1.25 parts butylene glycol, 0.1 parts dibutyltin dilaurate, 0.15 parts triethylenediamine, 2.4 parts silicone oil, and ultrapure water.

[0045] A method for preparing a porous polyurethane dermal scaffold includes the following specific steps: The preparation method of the above-mentioned porous polyurethane dermal scaffold includes the following steps: According to the above-mentioned weight proportions, polyethylene glycol was stirred for 0.5 hours; then, under stirring conditions, dibutyltin dilaurate, triethylenediamine, butanediol, and silicone oil were added slowly in sequence. After the addition was completed, stirring was continued for 0.5 hours to ensure thorough mixing and obtain a mixed solution; lysine diisocyanate and ultrapure water were added to the above mixed solution under rapid stirring and stirring was continued for 2 minutes; the stirred mixture was poured into a clean mold, quickly transferred to a 55°C environment for standing foaming and molding for 5 minutes and then cured for 2 hours; the cured sample was cooled, demolded, and washed with ultrapure water, then transferred to a 100°C oven to dry for 4 hours. After natural cooling, a polyurethane dermal support with a porous structure was obtained.

[0046] Comparative Example 1 The only difference from Example 1 is the modification of the ratio of hard to soft segments. By weight, the amount of lysine diisocyanate added is 42 parts and the amount of polyethylene glycol added is 30 parts. All other parameters and steps are the same as in Example 1.

[0047] Results: The porous polyurethane scaffold prepared in Comparative Example 3 had excessive hardness, lacked flexibility, and produced a lot of residue.

[0048] Comparative Example 2 The only difference from Example 1 is the modification of the ratio of the two catalysts. By weight, the amount of dibutyltin dilaurate added is 0.15 parts and the amount of triethylenediamine added is 0.1 parts. All other parameters and steps are the same as in Example 1.

[0049] Results: The porous polyurethane dermal scaffold prepared in Comparative Example 2 was hollow and leaky at the bottom, and the foam was brittle.

[0050] Comparative Example 3 The only difference from Example 1 is the change in the ratio of silicone oil to water. By weight, the amount of silicone oil added is 1.2 parts. All other parameters and steps are the same as in Example 1.

[0051] Result: The porous polyurethane dermal scaffold prepared in Comparative Example 3 could not be foamed and molded.

[0052] Comparative Example 4 The only difference from Example 1 is the modification of the chain extender ratio. The amount of butanediol added is 2.14 parts by mass. All other parameters and steps are the same as in Example 1.

[0053] Results: The porous polyurethane dermal scaffold prepared in Comparative Example 4 had uneven pores and poor elasticity.

[0054] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for preparing a porous polyurethane dermal scaffold, characterized in that, Includes the following steps: Dibutyltin dilaurate, triethylenediamine, butanediol and silicone oil were added sequentially to polyethylene glycol and mixed thoroughly to obtain a mixed solution. Lysine diisocyanate and ultrapure water were added to the mixed solution and mixed thoroughly to obtain a mixture; The mixture is placed in a mold and allowed to stand to foam and form. After curing, it is demolded, cleaned, and dried to obtain the porous polyurethane leather support.

2. The preparation method according to claim 1, characterized in that, The mass ratio of the lysine diisocyanate to the polyethylene glycol, butanediol, dibutyltin dilaurate, triethylenediamine, silicone oil, and ultrapure water is (45-50):(50-55):(1.2-1.25):(0.1-0.2):(0.15-0.3):(2.3-2.5):

1.

3. The preparation method according to claim 1, characterized in that, Before adding dibutyltin dilaurate, triethylenediamine, butanediol and silicone oil to polyethylene glycol and mixing them evenly, the process includes stirring the polyethylene glycol for 0.25-0.75 hours.

4. The preparation method according to claim 1, characterized in that, The method of adding dibutyltin dilaurate, triethylenediamine, butanediol and silicone oil to polyethylene glycol in sequence and mixing them evenly is to stir for 0.5-1 hours.

5. The preparation method according to claim 1, characterized in that, The lysine diisocyanate and ultrapure water are added to the mixed solution and stirred for 2-5 minutes.

6. The preparation method according to claim 1, characterized in that, The temperature for static foaming is 55-60℃, and the time for static foaming is 1-5 minutes.

7. The preparation method according to claim 1, characterized in that, The curing temperature is 55-60℃, and the curing time is 2-3 hours.

8. The preparation method according to claim 1, characterized in that, The drying temperature is 80-100℃, and the drying time is 3-5 hours.

9. A porous polyurethane dermal scaffold prepared by the preparation method according to any one of claims 1-8.

Images