CN117379598B - Polymer hydrogel and preparation method and application thereof - Google Patents
Polymer hydrogel and preparation method and application thereof Download PDFInfo
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- CN117379598B CN117379598B CN202310929426.4A CN202310929426A CN117379598B CN 117379598 B CN117379598 B CN 117379598B CN 202310929426 A CN202310929426 A CN 202310929426A CN 117379598 B CN117379598 B CN 117379598B
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K6/50—Preparations specially adapted for dental root treatment
- A61K6/56—Apical treatment
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Abstract
The invention relates to the technical field of polymer materials, and discloses a polymer hydrogel, a preparation method and application thereof, wherein the polymer hydrogel is prepared by the following steps: step 1, synthesizing a polypeptide structure KN-17; step 2, synthesizing a naproxen (Npx) -based polypeptide derivative Npx-FFEY, and step 3, co-assembling Npx-FFEY with KN-17 to synthesize a stable semitransparent high molecular hydrogel Npx-FFEY/KN-17; the polymer hydrogel can be used for promoting angiogenesis and regeneration of dental pulp-dentin complex, the novel antibacterial short peptide with antibacterial, dentin promoting and angiogenesis promoting functions is obtained by modifying the cecropin B polypeptide sequence, and the novel antibacterial short peptide is assembled with the polypeptide derivative Npx-FFEY together to obtain the injectable hydrogel without introducing any other chemical cross-linking agent, so that the preparation process is simple and has good biological safety.
Description
Technical Field
The invention relates to the technical field of high polymer materials, in particular to a high polymer hydrogel and a preparation method and application thereof.
Background
Dental trauma, pulpitis or periapical periodontitis are quite common during childhood and Root Canal Treatment (RCT) of young permanent teeth appears to be unavoidable. Normally, the root tip holes will gradually close within 3 years after the teeth erupt. For young permanent teeth, conventional root canal treatments have difficulty achieving proper root tip occlusion. However, some residual living pulp tissue and papilla cells remain viable in periapical tissue. Root tip induction molding is a well-known non-surgical treatment scheme for promoting root tip closure as a traditional treatment method for inducing young constant root tip closure. In recent decades, materials, particularly calcium hydroxide and mineral trioxide aggregates (Mineral trioxide aggregate, MTA), have been used for young permanent apices induction. Calcium hydroxide has demonstrated its effectiveness in inducing calcified root tip barriers with a success rate of 74-100%. However, the main drawback of calcium hydroxide is that it results in a reduced thickness or length of the root wall and a long period of time (6-24 months) is required to obtain a satisfactory root tip barrier effect. Subsequently, MTA gradually replaced calcium hydroxide for shortening the treatment time. However, MTA has similar drawbacks to calcium hydroxide, i.e. the continued development of the root cannot be induced and the tooth continues to have thin and fragile dentin walls. In addition, new bioceramic materials, such as Biodentine and EndoSequence Root Repair Materials (ERRM), have been marketed for root tip repair. Although bioceramic materials can shorten the root development cycle like MTA, there is little significant improvement in dentin wall thickness and hardness.
Regenerative pulp treatment has become an alternative treatment to promote continued development of young permanent roots. Young permanent teeth in which the root tip holes have not yet developed completely are considered to be a suitable choice, because the open root tip holes can ensure an adequate blood supply for the regeneration of the pulp-dentin complex. The basis of regenerative endodontic medicine is tissue regeneration using stem/progenitor cells, scaffolds and growth factors. This strategy aids in the deposition of hard tissue on the dentin wall, providing sufficient strength to the root to prevent cracking. Notably, the formation of new blood vessels is also critical for tissue regeneration, especially after ischemic injury of the tissue. Due to lack of oxygen or nutrient supply, tissue engineering strategies for pre-vascularization are not viable and in vivo vascularization may prove to be effective in regenerative endodontic medicine. Dental pulp revascularization can be considered a cell homing strategy that relies on the delivery of blood clots, growth factors, and stem cells from the root canal papilla (SCAP) as an intravascular stent structure, as their anatomical location is near the end of the root canal system. In addition, mesenchymal Stem Cells (MSCs) from various areas of the human body, including bone marrow, skin, and perivascular tissues, fat, and dental tissues, can also be induced into pulp-dentin complex.
In recent years, antibiotics and root canal occlusion drugs have led to an increasing resistance to bacteria, and conventional root tip induction molding has not achieved the expected effect. The antibacterial peptide is used as a novel antibacterial agent, has the advantages of low toxicity, high specificity and the like, has short interaction time, and reduces the occurrence probability of bacterial resistance. cecropin-B is one of the mature antibacterial peptide molecules in the current research, and has good antibacterial property and good promotion effect on the adhesion, growth and differentiation of osteoblasts. However, the natural antibacterial peptides have the following problems in clinical applications: 1) The amino acid sequence is long, and the stability is poor; 2) Has great cytotoxicity to mammals; 3) Industrial synthesis is costly and therefore often requires modification of the antimicrobial peptides to obtain the corresponding antimicrobial short peptides.
The hydrogel is a three-dimensional network structure gel with extremely hydrophilic property, has a crosslinked pore-shaped structure, has high water content and high viscoelastic property, provides good biosafety for the hydrogel, and is widely applied to the fields of drug delivery, tissue engineering and the like. The polymeric hydrogels can be placed in the pulp cavity and root canal for local administration in an effort to provide a 3D environment for the pulp-dentin complex while controlling drug release.
Disclosure of Invention
The invention aims to provide polypeptide structure KN-17, polymer hydrogel, a preparation method and application thereof, wherein the KN-17 is obtained by modifying cecropin B serving as a structure, so that the formation of new blood vessels can be promoted, and the technical problem that biological materials in the prior art have defects in the immature permanent tooth treatment process is solved.
The invention provides a preparation method of a high molecular hydrogel, which comprises the following steps:
step 1, synthesizing a polypeptide structure KN-17, wherein the amino acid sequence of the polypeptide structure KN-17 is shown as SEQ ID NO. 1;
step 2, synthesizing a naproxen (Npx) -based polypeptide derivative Npx-FFEY, wherein the structural formula of the polypeptide derivative Npx-FFEY is as follows:
step 3, npx-FFEY and KN-17 are assembled together to synthesize the stable semitransparent high molecular hydrogel Npx-FFEY/KN-17.
Further, in step 1, the polypeptide structure KN-17 is obtained by truncating the polypeptide sequence of cecropin B (cecropin B).
Further, in step 2, the polypeptide derivative Npx-FFEY is obtained by using 2-chlorotriacyl chloride resin as a phase carrier and different N-Fmoc protected amino acids as raw materials and adopting a solid phase peptide synthesis method.
Further, in step 3, the synthesis conditions are: adding KN-17 and Npx-FFEY into PBS buffer solution, adjusting pH to neutrality, heating until KN-17 and Npx-FFEY are dissolved, and cooling to obtain hydrogel Npx-FFEY/KN-17.
Further, in the PBS buffer, the minimum concentration of Npx-FFEY is 5mg/ml, and the concentration of KN-17 is 1-100 mu mol/L.
The invention also provides a high molecular hydrogel prepared by the preparation method of any one of the above
The invention further discloses the use of the hydrogel in promoting angiogenesis and regeneration of the pulp-dentin complex.
Compared with the prior art, the invention has the beneficial effects that:
(1) At present, medicines or materials for young permanent tooth root tip induction forming include calcium hydroxide paste, MTA, bioceramics and the like clinically, and the thickness and hardness of a dentin bridge cannot reach expected effects after 6-24 months after the root tip induction forming; the novel antibacterial short peptide with antibacterial, dentin promoting and angiogenesis promoting functions is obtained by modifying the cecropin B polypeptide sequence, and the regeneration of dental pulp-dentin complex can be effectively promoted.
(2) According to the invention, naproxen (Npx) is subjected to a polypeptide solid-phase synthesis method to prepare the polypeptide derivative Npx-FFEY, and can be subjected to co-assembly with KN-17 under heating-cooling to obtain the high polymer hydrogel, so that any other chemical cross-linking agent is not required to be introduced, the preparation process is simple, and the high polymer hydrogel has good biological safety.
(3) According to the preparation method of the injectable hydrogel, gelation can be realized by combining chemical and physical crosslinking under physiological conditions, the gelation time is short, rapid solidification can be realized within 30 minutes, clinical operation is easy, and the particle size distribution of the hydrogel is uniform.
(4) The novel self-assembled Npx-FFEY/KN-17 hydrogel can maintain the protein activity of the hydrogel under the regulation and control of temperature and enzyme in vivo, and can realize the purpose of long-term slow release of KN-17.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.
FIG. 1 is a graph showing the formation and characteristics of Nap-FFEY/KN-17 hydrogel provided by the invention;
FIG. 2 is a diagram showing the effect of Nap-FFEY/KN-17 hydrogel on odontogenic differentiation of DPSCs;
FIG. 3 is a graph showing the effect of KN-17-loaded hydrogels provided by the invention on the growth of enterococcus faecalis and the formation of a biofilm;
FIG. 4 is a graph showing the effect of Nap-FFEY/KN-17 hydrogel provided by the invention on neovascular regeneration and regeneration of rat molar marrow-dentin complex.
Detailed Description
The following description of the embodiments of the present invention will be made apparent and fully in view of the accompanying drawings, in which some, but not all embodiments of the invention are shown.
The components of the embodiments of the present invention generally described and illustrated in the figures herein may be arranged and designed in a wide variety of different configurations. Thus, the following detailed description of the embodiments of the invention, as presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention.
All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The embodiment of the invention provides a polypeptide structure KN-17, and the amino acid sequence of the polypeptide structure KN-17 is shown as SEQ ID NO. 1. The polypeptide structure KN-17 can promote the formation of new blood vessels.
On the basis, the invention discloses a self-assembled peptide-based cationic polymer hydrogel which contains the KN-17, and the finally prepared hydrogel can obviously promote angiogenesis and regeneration of dental pulp-dentin complex.
The preparation of the polymer hydrogel comprises the following steps:
step 1, synthesizing a polypeptide structure KN-17;
step 2, synthesizing a naproxen (Npx) -based polypeptide derivative Npx-FFEY, wherein the structural formula of the polypeptide derivative Npx-FFEY is as follows:
step 3, npx-FFEY and KN-17 are assembled together to synthesize the stable semitransparent high molecular hydrogel Npx-FFEY/KN-17.
Wherein, in step 1, the polypeptide structure KN-17 (KWKVFKKIEKMGRNIRN) can be obtained by truncating the polypeptide sequence of cecropin B (cecropin B).
In the step 2, the polypeptide derivative Npx-FFEY is obtained by taking 2-chlorotriacyl chloride resin as a phase carrier and different N-Fmoc protected amino acids as raw materials and adopting a solid-phase peptide synthesis method.
KN-17 in the examples of the present invention was synthesized by Shanghai benefiting Biotechnology Co., ltd (Shanghai), and the final peptide sequence was purified by High Performance Liquid Chromatography (HPLC) (purity > 95%) and confirmed by Mass Spectrometry (MS).
In a specific embodiment, the polypeptide derivative Npx-FFEY can be obtained by:
(1) The pharmaceutical intermediate Fmoc-Tyr (tBu) -OH (1 mmol) was mixed with 2-chlorotriacyl chloride resin (1 g) and 20ml dichloromethane solution, and reacted at room temperature for 1 hour to load it onto the 2-chlorotriacyl chloride resin. Subsequently, the Fmoc protecting group of the amino acid was cleaved by adding a solution of 20% piperidine in anhydrous DMF (N, N-dimethylformamide), washed 3 times with dichloromethane DCM, and washed 3 times with DMF.
(2) N, N-diisopropylethylamine DIEA (4 mmol) was added, benzotriazole-N, N, N ', N' -tetramethyluronium hexafluorophosphate HBTU (2 mmol) and Fmoc-Glu (OtBu) -OH (2 mmol) were reacted for 2 hours, after which the Fmoc protecting group of the amino acid was cleaved by addition of 20% piperidine in anhydrous DMF and washed three times with DMF.
(3) Fmoc-Phe-OH, fmoc-Phe-OH and Npx were ligated to the polypeptides according to step (2).
(4) The reaction solution was filtered off, and the residue was washed 5 times with 20mL of DMF each time, 5 times with dichloromethane in the same manner. With 95% trifluoroacetic acid (TrfluoroaceticAcid, TFA) (specific formulation: TFA:19mL, TIS:0.5mL, H) 2 O0.5 mL) the reaction time for cleavage of the polypeptide from the 2-chlorotriacyl chloride resin was 30 minutes. Finally, the solvent was spin-dried, 100mL of glacial ethyl ether was added, the precipitate was washed twice with glacial ethyl ether and dried by suction to give the crude product. The crude product is separated and purified by HPLC to obtain a pure product.
The nuclear magnetic resonance results were as follows: 1H NMR (500 MHz, dmso) delta 8.15-8.02 (m, 4H), 7.75-7.66 (m, 2H), 7.62 (s, 1H), 7.33 (dd, J=8.5, 1.8 Hz, 1H), 7.27-7.08 (m, 9H), 7.08-6.98 (m, 5H), 6.65 (d, 2H), 4.57-4.45 (m, 2H), 4.38-4.29 (m, 2H), 3.85 (s, 3H), 3.72 (q, J=6.9 Hz, 1H), 3.04-2.86 (m, 3H), 2.84-2.68 (m, 3H), 2.23 (t, J=8.2 Hz, 2H), 1.95-1.84 (m, 1H), 1.80-1.69 (m, 1H), 1.19 (d, J=8.84, 2H).
After KN-17 and Npx-FFEY are obtained, the concreteThe synthesis conditions are as follows: adding KN-17, npx-FFEY into PBS buffer solution, and adjusting pH to neutral, wherein NaCO can be used 3 Adjusting, heating until KN-17 and Npx-FFEY are dissolved, and cooling to obtain hydrogel Npx-FFEY/KN-17.
In the PBS buffer, the minimum concentration of Npx-FFEY was controlled to be 5mg/ml and the concentration of KN-17 was controlled to be in the range of 1-100. Mu. Mol/L in view of the final gel forming property.
As shown in FIG. 1, the polypeptide derivative Npx-FFEY is initially designed by a standard solid-phase multi-skin synthesis (SPPS) method and purified by a reversed-phase high-performance liquid chromatography method. Then, after heating and cooling Npx-FFEY and KN-17 at room temperature for 30 minutes, a stable translucent Npx-FFEY/KN-17 hydrogel was formed in PBS (pH 7.4) at a minimum concentration of 0.5wt (5 mg/ml) (FIG. 1A shows a schematic of a hydrogel formed by Nap-FFEY and KN-17). Subsequently, the properties and the characterization of the prepared polymer hydrogel were examined. Rheological testing (Rheologytest) is to examine the mechanical properties of hydrogels, and the results show that the storage modulus value (G') is always an order of magnitude greater than the loss storage value (G ") over a dynamic frequency sweep range of 0.1-100 rad/s, further demonstrating the formation of hydrogels (fig. 1B shows dynamic frequency sweeps of Nap-FFEY and Nap-EEFY/KN-17 hydrogels). The microscopic morphology of the resulting hydrogels was observed by TEM. The images showed that the hydrogel formed by Npx-FFEY self-assembly was "fibrous" and consisted primarily of crosslinked nanofibers, while the hydrogel formed by Npx-FFEY co-assembly with KN-17 was "spherical" (fig. 1C shows TEM images of Nap-FFEY and Nap-EEFY/KN-17 hydrogels). The experimental results clearly demonstrate the successful formation of a polymeric hydrogel with nanostructure and favorable tissue regeneration properties.
As shown in FIG. 2, after the successful construction of the polymer hydrogel, dental pulp mesenchymal stem cells (DPSCs) were extracted from adult mandibular third molar dental pulp tissue, and DPSCs were cultured in odontoblast medium. DPSCs were subjected to odontoblasts differentiation and ALP staining. FIG. 2A shows quantitative analysis of DPSCs gene expression levels after 2 weeks treatment with 1. Mu.M KN-17, 1. Mu.M Nap-FFEY/KN-17, 10mg/mL Nap-FFEY or PBS (Vehicle group), ALP staining after 2 weeks, and FIG. 2B shows KN-17. Mu. M, nap-FFEY/KN-17. Mu. M, nap-FFEY 10mg/mL or solvent treatment for 2 weeks, indicating that KN-17 and Npx-FFEY/KN-17 hydrogels significantly promote ALP activity and mineralization of DPSCs for up to 2 weeks. Furthermore, the expression of dentin-associated specific genes was investigated at the transcriptional level using the qPT-PCR method. qRT-PCR assay showed significant up-regulation of the transcription levels of dwarfism related transcription factor 2 (RUNX 2), ALP, dentin Sialophosphin (DSPP) and dentin matrix protein 1 (DMP-1) in KN-17 and hydrogel groups compared to the control group (i.e., vehicle and Npx-FFEY groups) (FIG. 2C shows quantitative analysis of gene expression levels after 2 weeks for KN-17. Mu.M, nap-FFEY/KN-17. Mu.M, nap-FFEY 10mg/mL or solvent treatment of DPSCs. The above results demonstrate the positive effect of KN-17 and the corresponding hydrogels on DPSCs odontogenic differentiation.
Enterococcus faecalis is typically isolated from infected root canal and survives without nutrition in the dental environment, as shown in figure 3. Because enterococcus faecalis has the capacity of forming a biological film, the removal difficulty of enterococcus faecalis is high, so that the growth and the colonization of enterococcus faecalis are effectively inhibited and are important for the regeneration of dental pulp-dentin complex. Crystal violet experiments showed that KN-17 and KN-17 loaded hydrogels significantly destroyed the biofilm formed by E.faecalis compared to the control group (FIG. 3A shows the growth of E.faecalis after 24h treatment with KN-17 mu M, nap-FFEY/KN-1710 mu M, nap-FFEY 10mg/mL or PBS (Vehicle group), FIG. 3B shows the bacteriostatic effect of KN-17 mu M, nap-FFEY/KN-17 mu M, nap-FFEY 10mg/mL or PBS (Vehicle group) on E.faecalis). In addition, the surface morphology of E.faecalis was examined by using a scanning electron microscope, and the E.faecalis cell membranes of KN-17 group and hydrogel group were subject to waving and rupture (FIG. 5C shows that E.faecalis biofilm formation was observed by using a scanning electron microscope with KN-17. Mu. M, nap-FFEY/KN-17. Mu. M, nap-FFEY 10mg/mL or PBS for 24 hours) as compared with the control group. The results show that KN-17 and Npx-FFEY/KN-17 have better antibacterial effect on enterococcus faecalis which infects the dominant bacteria in root canal, and the method also provides guarantee for regeneration of dental pulp-dentin complex.
Finally, as shown in fig. 4, the present invention also evaluates the effect of hydrogels in promoting angiogenesis and regeneration of pulp-dentin complex through in vivo experiments. In this study, we extracted the first molar of the upper jaw of SD rats, then performed the opening and the removal of the coronal pulp, only the root pulp remained, then KN-17, npx-FFEY, npx-FFEY/KN-17 and PBS (vehicle group) were placed into the pulp cavity of the dental coronal, respectively, and the cement closed the opening. The treated rat molar was placed in the subcutaneous tissue of the back of the BALB/C-nu mice (subcutaneous implantation) for 4 weeks of transplantation. The molars were removed 28 days later for HE staining, masson's trichrome staining and CD31 immunohistochemistry. As shown in FIG. 4B, the results showed that infection necrosis did not occur in the pulp in all of the 4 sets of molars. In the KN-17 and Npx-FFEY/KN-17 hydrogel sets, a newly formed matrix with a typical dentinal tubule structure was detected across the pulp cross section. Meanwhile, dental pulp tissue contains a large number of blood vessels. Compared with KN-17, the hydrogel group has a more compact dentin structure. Furthermore, as shown in fig. 4C, masson trichromatic staining showed that there was a small amount of irregularly blue-stained collagen fibers without mineralization in the dental pulp of the control group. The Npx-FFEY group blue-stained collagen fibers were barely visible. In contrast, in the KN-17 and hydrogel groups, mineralized blue fibrils were embedded in the pulp cross-section, and dentinal bridge calcification was clearly visible. Furthermore, CD31 immunohistochemistry was also used to detect angiogenesis. Immunohistochemical staining showed little CD31 expression in the control group. Fig. 4D shows immunohistochemical staining of rat molar tissue CD31 expression, and fig. 4E scoring CD31 expression according to histological score (h-score), with a significant increase in CD31 intensity around newly formed hard tissue in KN-17 and hydrogel groups compared to Npx-FFEY groups. In conclusion, the Npx-FFEY/KN-17 hydrogel as a high polymer biological scaffold material can effectively promote angiogenesis and regeneration of dental pulp-dentin complex, and provides a totally new thought for induction forming of young constant root tips.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (7)
1. The preparation method of the high polymer hydrogel is characterized by comprising the following steps:
step 1, synthesizing a polypeptide structure KN-17, wherein the amino acid sequence of the polypeptide structure KN-17 is shown as SEQ ID NO. 1;
step 2, synthesizing a naproxen (Npx) -based polypeptide derivative Npx-FFEY, wherein the structural formula of the polypeptide derivative Npx-FFEY is as follows:
step 3, npx-FFEY and KN-17 are assembled together to synthesize the stable semitransparent high molecular hydrogel Npx-FFEY/KN-17.
2. The method of preparation according to claim 1, wherein in step 1 the polypeptide structure KN-17 is obtained by truncating the polypeptide sequence of cecropin B (cecropin B).
3. The method according to claim 1, wherein in step 2, the polypeptide derivative Npx-FFEY is obtained by using 2-chlorotriacyl chloride resin as a phase carrier and different N-Fmoc protected amino acids as raw materials, and adopting a solid phase peptide synthesis method.
4. The method according to claim 1, wherein in step 3, the synthesis conditions are: adding KN-17 and Npx-FFEY into PBS buffer solution, adjusting pH to neutrality, heating until KN-17 and Npx-FFEY are dissolved, and cooling to obtain hydrogel Npx-FFEY/KN-17.
5. The method according to claim 4, wherein the minimum concentration of Npx-FFEY is 5mg/ml and the concentration of KN-17 is 1-100. Mu. Mol/L in PBS buffer.
6. A polymeric hydrogel produced by the method of any one of claims 1-5.
7. The use of the polymer hydrogel according to claim 6 for promoting angiogenesis and regeneration of dental pulp-dentin complex.
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CN114106094A (en) * | 2021-10-22 | 2022-03-01 | 天津市口腔医院(天津市整形外科医院、南开大学口腔医院) | Polypeptide, polypeptide derivative and nanofiber capable of inducing differentiation and mineralization of dentin of human dental pulp cells and application of polypeptide, polypeptide derivative and nanofiber |
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Inventor after: Zhao Borui Inventor after: Yu Yan Inventor after: Li Meng Inventor after: Zhang Qian Inventor before: Zhao Borui Inventor before: Guo Qingxiang Inventor before: Li Meng Inventor before: Zhang Qian |