Medicine for improving damaged bone regeneration in inflammatory immune microenvironment

Abstract

The invention belongs to the technical field of biological medicine, and particularly relates to a medicine for improving bone regeneration damage under an inflammatory immune microenvironment, the medicine comprises Kp7-6, the Kp7-6 promotes bone regeneration by antagonizing a Fas / FasL signal channel and reducing the apoptosis induction effect of immune cells on osteogenesis-related cells, the level of osteogenesis-related cell apoptosis mediated by the immune cells is reduced, and the osteogenesis-related cell apoptosis is improved. The stability of an osteoblast bank is maintained in a specific stage of bone repair, the volume fraction of new bones and the structural quality of bone trabecula are improved, and a new strategy with a clear mechanism is provided for treating diseases such as alveolar bone defects and inflammation-related bone defects.

Description

Technical Field

[0001] This invention relates to the field of medicine, specifically to a drug that improves bone regeneration impairment caused by an inflammatory immune microenvironment. Background Technology

[0002] Bone regeneration and repair is a highly complex and precisely regulated physiological process involving the interaction between the immune system and the skeletal system—a process known as bone immunology. In the early stages of physiological bone remodeling or repair following injury, a moderate inflammatory response is crucial for clearing necrotic tissue and recruiting repair cells. However, when the inflammatory response is excessive or persistent, creating an unfavorable inflammatory immune microenvironment, it severely disrupts the balance between bone formation and resorption, leading to delayed bone repair, decreased bone quality, and even difficulty in healing bone defects. These inflammation-related bone disorders are commonly found in diseases such as periodontitis, peri-implantitis, and osteomyelitis, posing a significant challenge to clinical treatment.

[0003] In this pathological process, abnormally activated immune cells (such as macrophages, T cells, and natural killer cells) release large amounts of pro-inflammatory cytokines, which not only directly inhibit osteoblast function but also induce apoptosis of osteoblast lineage cells through multiple signaling pathways, thereby depleting the critical osteoblast pool. Among these pathways, the Fas / FasL signaling pathway, as one of the core exogenous pathways of apoptosis, has received increasing attention. Fas is a death receptor; when its ligand FasL (mainly expressed on the surface of activated T cells, NK cells, and other immune cells) binds to it, it rapidly initiates an irreversible apoptosis program, which is an important mechanism for the body to clear abnormal cells. The Fas / FasL pathway plays a complex role in skeletal homeostasis and pathological processes, participating in the regulation of the survival and apoptosis balance of various bone remodeling-related cells, such as osteoblasts and osteoclasts. Especially in the inflammatory pathological microenvironment, activated immune cells can significantly overexpress FasL, acting on Fas receptors on the surface of key effector cells of bone repair, such as pre-osteoblasts in the differentiation stage, thereby potentially inducing their abnormal apoptosis and ultimately hindering the normal regeneration and healing process of bone tissue.

[0004] Several intervention tools have been developed targeting the Fas / FasL pathway. Among them, Kp7-6 is a known specific Fas / FasL signaling pathway antagonist. Chemically, it is a Fas mimetic peptide with the sequence Tyr-Cys-Asp-Glu-His-Phe-Cys-Tyr, forming an intramolecular disulfide bond between Cys2 and Cys7, and its molecular formula is C2. 48 H 56 N 10 O 15S2, with a molecular weight of 1077.15, is a small molecule compound. Kp7-6 competitively binds to FasL, inhibiting the formation of the Fas receptor-mediated death signaling complex, thereby effectively protecting cells from FasL-induced apoptosis. Current research mainly focuses on using this pathway antagonist to treat Fas-mediated liver injury or exploring its role in tumor immunomodulation. However, there is a complete lack of guidance or inspiration in the current technology for applying Kp7-6 or similar Fas / FasL pathway antagonists to regulate the local immune microenvironment of bone repair, specifically protecting osteoblasts and improving bone regeneration outcomes.

[0005] From a clinical perspective, the mainstream strategies for treating inflammation-related bone lesions, such as alveolar bone defects commonly found in the oral and maxillofacial region, include bone grafting, guided bone regeneration techniques, and the application of osteogenic factors, such as bone micronutrients (BMPs). These methods primarily focus on providing physical support or directly stimulating osteogenic activity, but they struggle to effectively regulate the persistent inflammatory immune microenvironment itself. Studies indicate that even with the introduction of osteogenic stimulating factors, impaired function or insufficient numbers of osteoblast-related cells can still lead to unstable treatment outcomes in the presence of persistent inflammation. Therefore, there is an urgent need in this field for a novel strategy that can precisely intervene in the local immune microenvironment of bone repair, protect osteoblasts from abnormal apoptosis induction, and thereby fundamentally improve the quality of bone regeneration.

[0006] In summary, although the role of the Fas / FasL pathway in immune apoptosis is well-established, and Kp7-6, as its antagonist, has been publicly disclosed, how to creatively apply this specific tool to address the technical challenge of impaired bone regeneration caused by excessive osteoblast apoptosis due to abnormal activation of immune cells in inflammatory bone lesions remains an unexplored area. Current technologies have neither revealed the key negative effects of this pathway within specific spatiotemporal windows of bone repair, nor provided any therapeutic options for promoting bone regeneration by targeting this pathway. Therefore, developing a novel therapeutic approach based on Fas / FasL pathway antagonism, aimed at improving impaired bone regeneration in the inflammatory immune microenvironment, has significant clinical and scientific value. Summary of the Invention

[0007] The purpose of this invention is to address the unsatisfactory bone regeneration and repair effects in the current clinical treatment of inflammatory bone diseases such as periodontitis, peri-implantitis, and osteomyelitis. It utilizes the Fas / FasL signaling pathway antagonist Kp7-6 to improve, promote, or treat impaired bone regeneration in the inflammatory immune microenvironment. Without interfering with the necessary and beneficial immune responses in the early stages of bone healing, it precisely intervenes in the immune microenvironment at specific critical stages of bone repair, effectively protecting osteoblast-related cells (such as pre-osteoblasts and osteoblasts) from excessive apoptosis induced by abnormal immune attacks, thereby fundamentally restoring and promoting the normal regeneration and healing process of bone tissue.

[0008] The technical solution for achieving the objective of this invention is: a drug that improves bone regeneration impairment in an inflammatory immune microenvironment, the drug containing Kp7-6, wherein Kp7-6 reduces the apoptosis-inducing effect of immune cells on osteoblast-related cells by antagonizing the Fas / FasL signaling pathway.

[0009] Furthermore, the immune cells are NK cells and / or T cells.

[0010] Furthermore, the osteogenic-associated cells are pre-osteoblasts and / or osteoblasts.

[0011] Furthermore, the inflammatory immune microenvironment is caused by inflammatory responses, abnormal activation of immune cells, or cytokine imbalance.

[0012] Furthermore, the impaired bone regeneration is selected from alveolar bone defects, inflammation-related bone defects, impaired bone healing, insufficient bone formation, or decreased bone structure quality.

[0013] Furthermore, it also includes pharmaceutically acceptable carriers.

[0014] Furthermore, the drug is administered during the bone formation and / or bone remodeling phase following bone injury.

[0015] Furthermore, the drug is administered via local administration.

[0016] Furthermore, the local administration is performed by local injection, implantation, or application to the bone defect site.

[0017] Furthermore, the dosage form of the local administration is an injection, gel, paste, sponge, film, or bone repair material loading agent.

[0018] Furthermore, the drug also contains one or more additional active ingredients selected from bone regeneration promoters, anti-inflammatory drugs, antibacterial drugs, or immunomodulators.

[0019] Another objective of this invention is to provide a kit for improving impaired bone regeneration in an inflammatory immune microenvironment, the kit comprising a first component and a second component, the first component comprising the Fas / FasL signaling pathway antagonist Kp7-6, and the second component comprising bone repair material or bone regeneration promoter.

[0020] Furthermore, the first component and the second component are configured to be applied separately or mixed before application. Beneficial effects

[0021] This invention proposes to use a known Fas mimic peptide, Kp7-6, as the core active ingredient. Kp7-6 acts as a specific Fas / FasL signaling pathway antagonist, competitively binding to FasL and inhibiting the formation of the death signal complex, thereby effectively protecting cells from FasL-induced apoptosis.

[0022] This invention is the first to propose the application of Kp7-6 in the field of bone repair. Through a local delivery system, it specifically blocks the Fas / FasL-mediated apoptosis pathway in the inflammatory microenvironment of bone defect sites, creating a protective microenvironment for the preservation and function of osteoblast pools.

[0023] The ultimate goal of this invention is not merely to inhibit apoptosis, but to synergistically enhance the effectiveness of existing bone regeneration strategies by relieving the inhibitory and killing effects of the immune microenvironment on osteoblasts. For example, when used in conjunction with bone repair materials or osteogenic factors, this invention ensures a sufficient number of functional osteoblasts responding to osteogenic stimuli, thereby improving the quality and stability of bone regeneration under complex pathological conditions such as diabetic bone defects and infected bone defects. It provides a new approach to addressing the clinical dilemma of unstable treatment efficacy even with the introduction of osteogenic stimulating factors when inflammation persists.

[0024] This invention provides a novel treatment method that targets the Fas / FasL apoptosis pathway, aims to specifically protect osteoblasts, and reshape the pro-regenerative immune microenvironment to address the key technical bottleneck of bone regeneration impairment caused by immune-mediated excessive osteoblast apoptosis in inflammatory bone diseases. It has significant clinical translational value and scientific significance.

[0025] This invention addresses a key pathological mechanism in inflammatory bone diseases where immune cells induce apoptosis of pre-osteoblasts and osteoblasts through high FasL expression, leading to bone loss. By applying FasL antagonists to block this apoptosis pathway, the invention aims to protect the osteoblast pool, increase bone mass, and promote bone regeneration. Attached Figure Description

[0026] Figure 1 Single-cell sequencing analysis revealed different types of immune cells and stromal cells within the inflammatory microenvironment of alveolar bone injury. FasL A violin diagram of gene expression levels.

[0027] Figure 2 For single-cell sequencing analysis, the NK cell population at different time points (e.g., day 3, day 14) during the bone regeneration and repair process were analyzed. FasL A violin diagram illustrating the dynamic changes in gene expression.

[0028] Figure 3The image shows the results of enrichment analysis of the set of genes highly expressed by NK cells during the bone repair period (day 14) based on the KEGG pathway database, which shows that they are significantly enriched in the "NK cell-mediated cytotoxicity" pathway.

[0029] Figure 4 The image shows the results of enrichment analysis of highly expressed genes in osteoblasts before the bone repair period (day 14) based on the KEGG pathway database, which shows that the genes are significantly enriched in the apoptosis pathway.

[0030] Figure 5 This is a schematic diagram of the chemical structure of compound Kp7-6 used in this invention.

[0031] Figure 6 This is a timeline diagram of the drug intervention regimens in the control group and the Kp7-6 treatment group during in vivo animal experiments.

[0032] Figure 7 This is a comparison of the results of quantitative analysis of new bone formation in the bone defect area after Micro-CT scanning, including indicators such as bone volume fraction (A), trabecular thickness (B), and trabecular separation (C).

[0033] Figure 8 The images show a comparison of microscopic photographs of tissue sections stained with hematoxylin and eosin (HE) in the bone defect area, visually demonstrating the differences in the amount of new bone matrix deposition and the density of trabecular bone structure between the Kp7-6 treatment group and the control group.

[0034] Figure 9 Representative fluorescence micrographs of tissues in bone defect areas after immunofluorescence staining for alkaline phosphatase (ALP, a pre-osteoblast marker).

[0035] Figure 10 To Figure 9 A bar chart showing the quantitative statistical analysis of the number of ALP-positive cells (pre-osteoblasts) in the immunofluorescence results.

[0036] Figure 11 Representative fluorescence micrographs of tissue in bone defect areas after dual immunofluorescence co-staining with ALP and Cleaved Caspase-3 (apoptosis marker).

[0037] Figure 12 To Figure 11 The bar chart shows the quantitative statistical analysis of the intensity of Cleaved Caspase-3 positive signal in preosteoblasts in the immunofluorescence results. Detailed Implementation

[0038] The following examples are for illustrative purposes only and are not intended to limit the scope of the invention. Where specific techniques or conditions are not specified in the examples, they should be performed according to the techniques or conditions described in the literature in this field, or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased from legitimate channels.

[0039] This invention provides a novel medical use for the known Fas / FasL signaling pathway antagonist Kp7-6: the preparation of drugs or medical devices that improve, promote, or treat impaired bone regeneration in an inflammatory immune microenvironment. This use is based on a profound understanding of bone immunology mechanisms, namely, the close dialogue between the immune system and the skeletal system, and that immune dysregulation is one of the important causes of impaired bone regeneration.

[0040] This invention innovatively expands the application of Kp7-6 from known areas such as liver injury protection to the field of bone repair, particularly targeting the pathological microenvironment where inflammation persists. During the repair phase after bone injury (especially during the active bone formation period), abnormally activated immune cells (such as natural killer cells and T cells) infiltrate the area and highly express FasL. These FasLs act on Fas receptors on the surface of osteoblast lineage cells (such as pre-osteoblasts and osteoblasts), thereby inducing excessive apoptosis, depleting the critical osteoblast pool, and ultimately leading to impaired bone regeneration and decreased bone quality. Kp7-6, as a Fas mimic peptide, can competitively bind to FasL, effectively blocking the Fas / FasL signaling pathway, thereby specifically protecting osteoblast-related cells from immune-mediated apoptosis without interfering with the essential inflammatory response in the early stages of bone healing, creating a favorable cellular microenvironment for bone regeneration.

[0041] Experimental materials and instruments: Compound Kp7-6 (purity >99%) was prepared in DMSO as a stock solution and diluted to the working concentration with 20% SBE-β-CD physiological saline solution before use. Experimental animals were SPF-grade 8-week-old male C57BL / 6 mice. The animal model was a standardized alveolar bone defect model. The main instruments were a micro-CT scanner (model: SCANCO μCT50) and a laser scanning confocal microscope (brand: NIKON). The above materials and instruments are only used to illustrate the embodiments of the present invention and do not constitute a limitation of the present invention. Example 1

[0042] A. The basis for drug design in this invention to improve impaired bone regeneration in the inflammatory immune microenvironment.

[0043] a) Single-cell transcriptome sequencing analysis was performed on cells in the alveolar bone injury area, and the results are as follows: Figure 1 As shown, different immune cells and stromal cells exhibit differences during inflammation-related bone repair. FaslGene expression characteristics. Further analysis showed that at specific time points in bone repair (e.g., day 14 post-injury), infiltrating NK cell subsets were specifically highly expressed. Fasl The genes suggest that FasL, derived from NK cells, may be involved in the regulation of intercellular communication during this period.

[0044] b) Analysis of NK cell and pre-osteoblast functional status: KEGG pathway enrichment analysis was performed on the set of highly expressed genes in NK cells at the above time points. For example... Figure 3 As shown, their overall gene expression characteristics are significantly enriched in NK cell-mediated cytotoxic pathways. This functionally suggests that NK cells at this stage are in an activated state, inducing target cell apoptosis through pathways such as FasL / Fas. KEGG analysis of pre-osteoblasts at the same stage is shown below. Figure 4 As shown, the highly expressed gene was significantly enriched in the apoptosis pathway, suggesting that pre-osteoblasts initiate apoptosis-related molecular programs in the repair microenvironment and are more sensitive to the external death signal FasL. These analytical results provide experimental basis for selecting the Fas / FasL signaling pathway as an intervention target. These results, based on NK cell-related analysis, illustrate the relationship between immune cell-mediated signaling and osteoblast-related cell apoptosis in the inflammatory immune microenvironment; in other inflammatory immune backgrounds, different types of immune cells may also participate in the regulation of osteoblast-related cell survival status through similar signaling pathways.

[0045] c) Selection of intervention tools: Based on the above findings, the known specific Fas / FasL signaling pathway antagonist peptide Kp7-6 (structure shown in...) was selected. Figure 5 This was chosen as an intervention tool. The purpose was to verify whether modulating the Fas / FasL signaling pathway could improve bone regeneration within the inflammatory immune microenvironment.

[0046] B. Validation of the in vivo therapeutic efficacy of the drug of the present invention in improving bone regeneration impairment in the inflammatory immune microenvironment: A standard mouse model of alveolar bone defect in the maxillary molar region was established. Mice were randomly divided into a model control group (receiving an equal volume of 20% SBE-β-CD saline solution) and a Kp7-6 treatment group (receiving Kp7-6 solution). The administration regimen was as follows: Figure 6 As shown, drug administration began on day 3 after modeling and was repeated every 3 days via intraperitoneal injection at a dose of 10 mg / kg. Animals were sacrificed on day 14 after modeling, and bone tissue from the defect area was collected for evaluation. The above-described administration method, timing, and dosage are merely one embodiment of the present invention.

[0047] a) Micro-CT quantitative evaluation: Micro-CT scanning and three-dimensional morphometric analysis of the bone defect area, such as... Figure 7As shown, compared with the control group, the Kp7-6 treatment group showed significantly improved new bone mass and quality. Specifically, this was manifested in increased bone volume fraction, significantly increased trabecular thickness, and significantly decreased trabecular separation (all comparative quantitative analyses, P <0.001).

[0048] b) Histological morphological evaluation: HE staining of the bone defect area, such as... Figure 8 As shown, the Kp7-6 treatment group had a large amount of eosinophilic new bone matrix uniformly deposited in the bone defect area, forming a continuous and dense trabecular bone structure; while the control group had sparse new bone trabeculae.

[0049] C. Verification of the drug mechanism of action of this invention in improving impaired bone regeneration in the inflammatory immune microenvironment: a) Effect on the number of pre-osteoblasts: Immunofluorescence staining was used to detect the pre-osteoblast marker ALP, and the results are as follows: Figure 9 and Figure 10 As shown, the number of ALP-positive cells in the defect area of ​​the Kp7-6 treatment group was significantly higher than that of the control group (quantitative analysis P<0.001), suggesting that Kp7-6 can effectively maintain the number of pre-osteoblasts in the repair area.

[0050] b) Inhibition of pre-osteoblast apoptosis: ALP and Cleaved Caspase-3 dual immunofluorescence staining were used, and the results are as follows... Figure 11 and Figure 12 As shown, in the control group, a large number of ALP-positive cells simultaneously expressed Cleaved Caspase-3; while in the Kp7-6 treatment group, the signal intensity of Cleaved Caspase-3 in pre-osteoblasts was significantly reduced (quantitative analysis P<0.05). These results indicate that Kp7-6 treatment is correlated with a decrease in pre-osteoblast apoptosis levels, supporting its role in improving bone regeneration. It can be seen that in an inflammation-related bone defect model, the application of the Fas / FasL signaling pathway antagonist Kp7-6 during the bone repair stage helps reduce immune cell-mediated osteoblast-related cell apoptosis levels and improves the quantity and structural quality of newly formed bone. The above experimental results are used to illustrate the technical effects of the present invention and do not constitute a limitation on the scope of protection of the present invention.

[0051] Those skilled in the art should understand that the above embodiments are merely examples illustrating the core principles of the present invention, and the scope of protection of the present invention is not limited thereto. Various modifications and combinations can be made without departing from the concept of the present invention: Bone regeneration impairment under the inflammatory immune microenvironment described in the indications includes, but is not limited to, insufficient bone formation, delayed bone repair, or decreased bone quality caused by periodontitis, peri-implantitis, osteomyelitis, post-traumatic infected nonunion, etc. Administration is preferably carried out after bone injury, during the active phase of bone formation and / or bone remodeling, to precisely intervene in pathological apoptotic signals while avoiding interference with early beneficial inflammatory responses. Routes of administration and dosage forms include, but are not limited to, local injection, implantation, coating, or systemic administration. The drug can be formulated into dosage forms suitable for local administration, such as injectable hydrogels, bone repair sponges, films, or loaded onto the surface or interior of bone graft materials (such as hydroxyapatite, β-tricalcium phosphate). Kp7-6 can be used in combination with one or more other active ingredients to prepare compound drug compositions or combination therapy kits. For example, it can be used in combination with bone regeneration promoters such as bone morphogenetic proteins and fibroblast growth factors, or with anti-inflammatory drugs such as nonsteroidal anti-inflammatory drugs and glucocorticoids, to achieve synergistic effects. The effective therapeutic dose can be routinely adjusted according to factors such as the patient's age, weight, disease severity, and route of administration.

[0052] This invention provides a novel medical application for the known Fas / FasL pathway antagonist Kp7-6, to improve impaired bone regeneration in an inflammatory immune microenvironment, opening up new application areas for this compound. At specific stages of bone repair, FasL signaling derived from inflammatory immune cells can induce excessive apoptosis in osteoblast-associated cells, inhibiting bone regeneration. This invention proposes that by intervening in this pathway with Kp7-6, the level of apoptosis in osteoblast-associated cells can be selectively reduced without affecting the inflammatory response required in the early stages of bone repair.

[0053] The drug provided by this invention has a clear target and stage specificity, and can improve the quantity and structural quality of new bone, providing a new approach with a clear mechanism and precise intervention for the treatment of inflammatory bone diseases. Animal experimental results show that the drug of this invention can increase the bone volume fraction of new bone, improve trabecular bone structural parameters (increased trabecular thickness, decreased trabecular spacing), and promote the formation of denser and more mature new bone tissue, showing good application prospects.

[0054] Traditional strategies for promoting bone regeneration often focus on directly stimulating osteoblast differentiation or supplementing osteogenic factors, such as BMPs. This invention precisely blocks FasL, a specific signal that leads to osteoblast death. Unlike enhancing immune killing as in cancer treatment, it selectively counteracts the immune system's accidental damage to osteoblasts. By targeting FasL, a key molecule at the immune cell-osteoblast interface, it achieves remarkable precision. The aim is to transform it from a destructive force to a protective one. Unlike simple anti-inflammatory treatments, it does not comprehensively suppress the immune system but precisely intercepts a specific destructive signal, resulting in greater safety. This is the first systematic proposal to use it in the treatment of diseases characterized by impaired bone regeneration, representing a significant drug repositioning.

[0055] The Fas / FasL pathway plays a complex role in bone homeostasis regulation and is a detrimental factor in inducing apoptosis. Current technology suggests that FasL expressed by osteoblasts is crucial for inducing osteoclast apoptosis and is a necessary physiological process for maintaining normal bone mass. Systemic or non-specific inhibition of FasL function may lead to uncontrolled osteoclast activity, thereby exacerbating bone loss. Furthermore, some studies suggest that the Fas / FasL system may inhibit osteoblast differentiation. Those skilled in the art could not have foreseen that, in the complex pathological environment of inflammation, the ultimate effect of Fas / FasL antagonism would be to promote bone regeneration, rather than disrupting the balance of bone remodeling and leading to worse outcomes.

[0056] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention. The above description of specific embodiments of the present invention is intended to illustrate, rather than limit, the concept of the present invention. For those skilled in the art, any equivalent substitutions, modifications, or improvements made without departing from the principles of the present invention should be considered to fall within the protection scope of the present invention as defined by the appended claims. Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions, and variations to the above embodiments within the scope of the present invention.

Claims

1. A medicament for improving impaired bone regeneration in an inflammatory immune microenvironment, characterized by, The drug comprises Kp7-6, which reduces the apoptosis-inducing effect of immune cells on osteogenesis-related cells by antagonizing the Fas / FasL signaling pathway.

2. The medicament according to claim 1, characterized in that, The immune cells are NK cells and / or T cells.

3. The medicament according to claim 1, characterized in that, The osteogenesis-related cells are pre-osteoblasts and / or osteoblasts.

4. The medicament according to claim 1, characterized in that, The inflammatory immune microenvironment is caused by inflammatory response, abnormal activation of immune cells, or imbalance of cytokines.

5. The medicament according to claim 1, characterized in that, The impaired bone regeneration is selected from alveolar bone defect, inflammation-related bone defect, bone healing disorder, insufficient osteogenesis, or decreased bone structure quality.

6. The medicament according to claim 1, characterized in that, It further comprises a pharmaceutically acceptable carrier.

7. The medicament according to claim 1, characterized in that, The drug is administered in the osteogenesis stage and / or bone remodeling stage after bone injury.

8. The medicament according to claim 1, characterized in that, The drug is administered locally.

9. The medicament according to claim 8, characterized in that, The local administration is local injection, implantation, or coating at the bone defect site.

10. The medicament according to claim 8, characterized in that, The dosage form of the local administration is injection, gel, paste, sponge, film, or bone repair material loading.

11. The medicament according to claim 1, characterized in that, It further comprises one or more additional active ingredients selected from bone regeneration promoters, anti-inflammatory drugs, antibacterial drugs, or immunomodulators.

12. A kit for improving impaired bone regeneration in an inflammatory immune microenvironment, characterized in that, The kit comprises a first component and a second component, the first component comprising Kp7-6; and the second component, the second component comprising a bone repair material or a bone regeneration promoter.

13. The kit of claim 12, wherein The first component and the second component are configured to be administered separately or after mixing.

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