HYDROGELS FOR BONE TISSUE REPARING BY RADIATION METHOD (1) (1) (2).docx

**HYDROGELS FOR BONE TISSUE REPARING BY RADIATION METHOD** Tanuja Wankhade^1^ Tejaswini Mankar^2^ Pranav Mapari^3^ Yash Mande^4^ Ankit Makhamale^5^ Kunal Mahajan^6^ Assistant Professor^1^ UG student^2^ UG student^3^ UG student^4^ UG student^5^ UG Student^6^ **1.Abstract** In this study, the comp...

**HYDROGELS FOR BONE TISSUE REPARING BY RADIATION METHOD** Tanuja Wankhade^1^ Tejaswini Mankar^2^ Pranav Mapari^3^ Yash Mande^4^ Ankit Makhamale^5^ Kunal Mahajan^6^ Assistant Professor^1^ UG student^2^ UG student^3^ UG student^4^ UG student^5^ UG Student^6^ **1.Abstract** In this study, the composite hydrogels containing hydroxyapatite (HAP) nanoparticles (NPs) for bone tissue engineering were fabricated using gamma-ray irradiation treatment.^1^ Hydrogel was examined by SEM imagery and energy dispersive X-ray spectrophotometry, and the crystalline structure of SF composite hydrogels was also confirmed by X-ray Diffractometry. Bones provide mechanical protection for the body (such as protecting internal organs and blood forming marrow), facilitate locomotion, and serve as a reservoir for calcium, magnesium and phosphate minerals. Osteogenesis often requires a for replacement graft to restore the function of damaged tissue. Bone tissue engineering offer a promising alternative treatment for medical use, as well as a controllable system for studies of biological function, development of biology and pathogenesis. Bone tissue repair has garnered significant attention in regenerative medicine.^30^ Hydrogels, due to their biocompatibility, versatility, and ability to mimic the extracellular matrix, have emerged as promising candidates for bone repair. This review focuses on recent advances in using Radiation methods offer precise control over hydrogel properties, which can be crucial for bone tissue engineering, highlighting key methodologies and the challenges. Radiation techniques including gamma radiation, electron beam and UV radiation are employed to cross link polymer chains, thereby enhancing the mechanical properties and stability of hydrogels.^27^Challenges and feature directions in the fields are highlighted, emphasizing the need for optimizing radiation parameters and hydrogel formulations to achieve better clinical outcomes. This review provides a comprehensive overview of the state- of -- the- art radiation method in hydrogel development and their implications for advancing bone tissue repair technologies. **2.Keywords** Hydrogels, Biocompatibility, Radiation cross-linking, Bone tissue repairing, Electron beam, Scaffold, Irradiation **3.Introduction** Significant health problems arise due to bone defects resulting from tumors, diseases, infections, biochemical disorder, trauma and abnormal skeleton development.^2^ Bone tissue engineering has significant advancement in recent years, driven by the need for effective strategies to repair and regenerate damage bone tissues. Hydrogels, three dimensional networks of hydrophilic polymers capable of retaining substantial amount of water, have emerged as a versatile solution in this field. Their inherent properties, such as high biocompatibility tunable mechanical characteristics, and the ability to support cell growth make them ideal candidate for bone tissue application.^10^ Bones provide mechanical protection to the body, facility locomotion, and they serve as a reservoir for calcium, magnesium and phosphate minerals. Numerous research efforts have addressed the development of an ideal scaffold for bone tissue engineering; however, they still have several limitations. For brain drug delivery and nerve regenerative engineering, polysaccharide base gels have been explored. Hydrogel materials have natural advantages compares with other bioactive materials in bone tissue repair engineering. Hydrogels enable adhesion, proliferation and differentiation properties of stem cells during bone tissue repair.^4^ Among various methods for hydrogel fabrication, radiation techniques have gained attention due to their ability to precisely control the cross-linking of polymer chains, radiation methods including gamma rays, electron beams and UV light, enable the creation of hydrogels with tailored properties essential for bone tissue engineering.^8^ this technique of several advantages such as uniform cross-linking, reduced reliance on chemical initiators, and enhanced control over the physical and chemical properties of hydrogels. This introduction explores the principles behind radiation- induced hydrogel synthesis and modification, outlining how this method contributes to the development of advanced material for bone repair.^12^ This review aims to provide an understanding of impact of radiation technique on hydrogel properties and their potential applications in regenerative medicines. **4.Hydrogels in Bone Tissue Engineering** **5.Types of Hydrogels** Common types are natural like collagen, alginate and synthetic like polyethylene glycol, polyvinyl alcohol, hydrogels. Each types has unique advantages in terms of degradation rates, mechanical properties, and biological interactions.^14^ **Fig No.2 TYPES OF HYDROGELS** The hydrogels classification depends on various types such as sources, composition, configuration, cross- linking, ionic charge, response, degradability, physical property  Fig No.3.TYPES OF HYDROGELS BY GENERATION 6.Radiation methods for hydrogel modification: Radiation Techniques are pivotal in modifying hydrogels to enhance their properties for biomedical applications, particularly in tissue engineering.to induce cross-linking these methods involve various forms of Radiation. The new ionization Radiation method is use recently for hydrogels modification. Radiation methods are used to modify hydrogels in a variety of ways includes: 6.1. Radiations cross linking: In this Induces a cross-linking reaction between Polymer chains in the method.^9^ 6.2. Radiations Polymerization: In this generates free radicals from monomers in the method.^13^ 6.3. Radiations Grafting. This method causes the polymer to produce radicals f graft Copolymerization.^13^ Hydrogel fabrication using gamma radiation involves applying high-energy gamma rays to induce crosslinking within hydrophilic polymer networks. This method utilizes isotopes like cobalt-60 to uniformly crosslink the polymer chains, transforming the precursor solution into a stable, three-dimensional hydrogel.^17^ 1.Gamma Radiation: Process: Gamma rays, emitted from radioactive isotopes like Cobalt-60, penetrate the hydrogel and induce ionization of polymer chains. Effects: This ionization leads to the formation of free radicals, which then initiate cross-linking reactions between polymer chains. Gamma radiation allows for uniform cross-linking throughout the hydrogel, improving its mechanical properties and stability. Advantages: It offers high penetration depth, making it suitable for bulk hydrogel processing. Additionally, it requires no chemical initiators, minimizing potential cytotoxicity. 2.Electron Beam (E-beam) Radiation: Process: High-energy electron beams are directed aat the hydrogel, causing ionization and the creation of free radicals. Effects: Similar gamma radiation, the free radicals facilitate cross-linking between polymer chains. E-beam radiation is known for its high efficiency and rapid processing times. Advantages: It provides precise control over the degree of cross-linking and is effective for high-throughput production. It also allows for deep penetration into thicker hydrogels. 3.Ultraviolet (UV) Radiation: Process: UV light, typically from mercury lamps or LEDs, is used to irradiate hydrogels containing photo initiators. Effects: Photo initiators absorb UV light and generate free radicals, which initiate cross-linking in the presence of suitable monomers. This method allows for the creation of hydrogels with specific patterns or shapes through mask-based techniques. Advantages: UV radiation enables rapid and localized cross-linking, which is useful for fabricating hydrogels with complex geometries or surface modifications. 4.Combination Techniques: Process: Combining different radiation methods, such as gamma and UV radiation, can further optimize hydrogel properties. Effects: This approach can enhance cross-linking density, adjust swelling behaviour, and incorporate functional groups more effectively. Advantages: It offers increased flexibility in tailoring hydrogel properties for specific applications. Fig No.4.RADIATION TECHNIQUES Radiation methods can be used to create hydrogels with specific properties for various applications. For example, gamma irradiation can be used to synthesize polyacrylic acid-co-polyacrylamide hydrogels, which can then be chemically modified to remove metal ions from polluted water.^21^ 7.Applications Of Hydrogels in Tissue Engineering: 7.1. Enhances Mechanical Properties: Radiation-induced cross-linking improves the strength and elasticity of hydrogels, which is crucial for supporting and regenerating bone tissue.^17^ 7.2. Controlled Degradation Rates: By adjusting radiation parameters, the degradation rate of hydrogels can be fine-tuned to match the rate of bone healing. Incorporation of Bioactive Agents: Radiation methods facilitate the integration of bioactive molecules into hydrogels, promoting cell growth and bone formation. in summary, radiation methods provide a versatile and effective means of modifying hydrogels to meet the specific requirements of bone tissue engineering, offering benefits in terms of mechanical performance, stability, and bioactivity.^20^ 7.3. Scaffolds: Hydrogels can mimic extracellular matrices and provide structural integrity for cells to organize and grow.   7.4. cell encapsulation and delivery: The Hydrogel can encapsulate and deliver cells.   7.5. Tissue barriers and bio adhesives: Hydrogels can act as tissue barriers and bio adhesives.   7.6. Drug depots: Hydrogels can serve as depots for drugs.   7.7. Bioactive moiety delivery: Hydrogels can deliver bioactive moieties to encourage the natural reparative process.  7.8 Regenerating artificial cartilage: PVA hydrogels can be used to regenerate artificial articular cartilage.   Bone-like apatite formation: PVA hydrogels can be used to form bone-like apatite.   7.9. Treating spinal cord injuries: Hydrogels can stabilize the inflammatory environment at the lesion site and provide a suitable environment for regeneration.   7.10. Regenerating tissue lost after brain injuries: Hydrogels can be an alternative to regenerating tissue lost after brain injuries.^11^ 7.11. Hydrogels Inspired by the Extracellular Matrix: To preserve the structural integrity of tissues, the ECM of native tissues provides physical support.it serves as an adhesive substrate for the attachment and organization of cells, and as a reservoir for biochemical cues to support cell survival and differentiation.^7^ 7.12. Photopolymerized hydrogels in tissue engineering: It has been Use in a wide range of Biomedical applications. in tissue engineering , Hydrogels have been used to alter and improve tissue function, for instance, by functioning as tissue barriers and have also been investigated for use as cell carrier materials for the tissue replacement strategies.^17^ 7.13. Bones Regeneration: Hydrogels modified by radiation can support the attachment, proliferation, and differentiation of osteoblasts, enhancing bone regeneration. 7.14. Delivery Systems: Radiation-modified hydrogels can serve as carriers for growth factors, drugs, or genes that promote bone healing. 7.15 Scaffold Integration: These hydrogels can be integrated with other materials like ceramics or metals to improve their mechanical properties and suitability for load-bearing applications. 8.Advantages of Radiation Method: 8.1. Radiations-induced polymerization: A Radiation -induced penetrating polymerization method can create hydrogels that combine the best feature of elastomers and hydrogels. these can have similar young s modulus and friction coefficients to human skin, and they can withstand better compression and puncture loads.^13^ 8.2. Tissue Adhesion: Hydrogels have good tissue adhesion and shape Adaptation, and this is excellent property of the hydrogels. 8.3 Sterilization: Efficiency: Radiation can effectively sterilize equipment and materials, killing bacteria, viruses, and other pathogens.^19^ Penetration: It can penetrate through packaging and materials, making it suitable for sterilizing items that are difficult to clean with other methods. No Residues: Unlike chemical sterilization, radiation does not leave harmful residues on products. 8.4. Imaging: Detailed Images: In medical imaging (like X-rays and CT scans), radiation provides detailed internal images of the body, aiding in diagnosis and treatment planning. Non-Invasive: Allows for internal examination without the need for invasive procedures. 8.5. Therapy: Targeted Treatment: In cancer treatment (radiotherapy), radiation can precisely target and destroy cancer cells while minimizing damage to surrounding healthy tissue. Effective for Specific Types: Effective for certain types of cancers and conditions that are less responsive to other treatments. 8.6. Industrial Applications: Non-Destructive Testing: Radiation is used in non-destructive testing to inspect the integrity of materials and structures without damaging them. 8.7 Preservation: Food Preservation: Radiation can extend the shelf life of food by killing spoilage organisms and pests. Each application of radiation has its own specific advantages, but it's essential to manage and control radiation use carefully to minimize potential health risks and environmental impacts. 8.8Therapeutic reagent delivery: Hydrogels can be used as on demand it is intelligent delivery system to release therapeutic reagents. 8.9 Self-healing: Hydrogels have the self -healing properties 8.10 Radioprotection: Hydrogels can be used to protect form against radiation damage. For example, hydrogels can be implanted between the prostate and the rectum to increase the radiation dose to the prostate while minimizing rectal injury.^22^ 8.11 Mechanical and biochemical properties: Hydrogels have excellent mechanical and biochemical properties, including the antibacterial, antioxidant, and adhesive abilities. 8.12 ECM-derived hydrogels: Hydrogels derived from the extracellular matrix (ECM) can help repair injured tissues. For example, can help with pulmonary damage and oedema after radiation exposure the lung ECM-derived hydrogels use.^21^ 8.13 Platelet-rich hydrogels: Platelet rich hydrogels can help protect against radiation -induced dermatitis and bone injury. Precision and Control: Radiation allows for precise control over the crosslinking density and network structure of hydrogels, leading to improved mechanical strength and stability.^20^ Reduced Chemical Usage: Unlike chemical crosslinking agents, radiation methods do not introduce potentially toxic residues into the hydrogel. Customization: The extent and type of crosslinking can be adjusted to meet the specific requirements of different bone repair applications Frontiers \| Hydrogels for Tissue Engineering: Addressing Key Design Needs Toward Clinical Translation Fig No.5.ADVANTAGES OF TISSUE ENGINEERING 9.Prepared for bone tissue repair using radiation: 9.1 Photo-cross-linking: A photo-cross-linked osteogenic growth peptide (OGP) and gelatin (GelMA) were used to create a novel osteogenic polypeptide hydrogel (GelMA-C-OGP) using ultraviolet radiation. This hydrogel can promote bone regeneration by increasing calcium salt precipitation in osteoblasts and enhancing the expression of osteoblast-related genes. 9.2 Gamma or electron beam irradiation: High-energy radiation can cross-link water-soluble polymer or monomer chain ends without the need for a cross-linker. This method can be performed at room temperature and physiological pH, but the radiation can damage cells and tissues. 9.3 UV light irradiation: Liquid hydrogels and BMSCs were co-cultured with Factor A and Factor B, and then cured with UV light irradiation. This hydrogel mixture was used to fill osteochondral defect areas in layers. 9.4 Sol-gel method: This method was used to prepare a thermosensitive chitosan-based hydrogel reinforced with nano hydroxy apatite. 9.5 3D printing: This microfabrication technique can create 3D structures with the desired architecture or shape. 10.Challenges and Future Directions: 10.1Challenges: Fig No.6.CHALLENGES OF HYDROGELS BY RADIATION METHOD 10.1.1 Radiation Sensitivity: Hydrogels can be sensitive to radiation, which can alter their physical and chemical properties, Potentially Affecting their performance in bone repair 10.1.2 Biocompatibility: Ensuring the Hydrogels remain biocompatible after radiation-induced modifications is crucial. could Compromise their effectiveness by unwanted side effects or toxicity. 10.1.3 Controlled Cross-linking: Achieving precise control over the cross-linking density of hydrogels through radiation in challenging but essential for maintaining the mechanical properties of necessary for bone repair.^26^ 10.1.4 Degradation: The degradation of hydrogels under physiological conditions can be difficult to control. 10.1.5 Lead bearing capacity: Hydrogels need to have adequate mechanical strength to support bone repair. Ensuring achieves the desired strength without compromising the hydrogels other properties is a significant challenge in radiation method. 10.2 Future Directions: 10.2.1 Advanced Radiation Techniques: Development of more precise and controlled radiation techniques could improve the cross-linking process and minimize unwanted changes in the hydrogel properties. 10.2.2 Hybrid Materials: Combining hydrogels with other materials or bioactive agents could enhance their performance. For instance, incorporating nanoparticles or growth factors might improve both their mechanical strength and biological functionality.^25^ 10.2.3 Customization and Optimization: Tailoring hydrogels for specific types of bone defects and repair requirements through radiation-induced modifications could lead to more effective treatments. 10.2.4 Long-term Studies: More research is needed on the long-term effects of radiation-processed hydrogels in biological systems, including their stability, degradation, and interaction with surrounding tissues. 10.2.5 Clinical Trials: Progressing from laboratory research to clinical trials will be crucial in assessing the real-world applicability and safety of radiation-processed hydrogels for bone tissue repair. These advancements could significantly enhance the utility of hydrogels in regenerative medicine, offering better solutions for bone repair and regeneration. 10.2.6 Long-term Stability: Ensuring that the hydrogels maintain their properties over extended periods and in physiological conditions is crucial for clinical applications.^24^ 10.2.7 Regulatory and Safety Aspects: Addressing regulatory concerns and ensuring the safety of radiation-modified hydrogels in clinical settings are important for their successful translation to the clinic. 11.Conclusion: Radiation methods offer a powerful tool for enhancing the properties of hydrogels used in bone tissue engineering. By providing precise control over crosslinking and minimizing chemical additives, these methods hold significant promise for developing effective and safe materials for bone repair. Ongoing research is needed to address current challenges and fully realize the potential of radiation-modified hydrogels in clinical applications. Hydrogels created via radiation methods have shown significant promise for bone tissue repair due to their unique properties, such as biocompatibility, controlled degradation, and the ability to be tailored for specific applications. The radiation-induced crosslinking techniques offer precise control over the hydrogel\'s mechanical strength and porosity, which are crucial for effective bone regeneration. Future research should focus on optimizing these hydrogels by exploring various radiation parameters, incorporating bioactive agents, and conducting extensive in vivo studies to better understand their long-term efficacy and safety in clinical settings. Advances in this field could lead to more effective and personalized treatments for bone repair and regeneration. 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