Due to their varied structures and compositions, nanomaterials have enriched many biomedical applications. Nanomaterials have recently been implemented in the study of bone disorders. Biological tumour imaging, crack development detection, arthritis metabolomics sensors, targeted delivery, and complication prevention are just some of the emerging fields of nanomaterials for the diagnoses and treatment of bone-related diseases ^[1][30]. Natural-origin polymers like chitosan (CHT) and chondroitin sulphate (CS) are viable alternatives to the organic template because of their structural similarities to the extracellular environment (ECM), chemical versatility, and favourable biocompatibility ^[2][31]. Potentially useful for preventing spoilage in refrigerated grass carp, PC encapsulated NPs added to CS bio-films reduced bacterial and oxidation-induced spoilage ^[3][32]. Due to the small identity potential of the bone and cartilage tissues, cartilage repair following trauma or degenerative diseases like osteoarthritis (OA) remains a major challenge in modern medicine. Cryo-biomaterials made of marine collagen, chitosan, fucoidan, and chondroitin sulphate are infused with primary human cells for cartilage tissue engineering ^[4][33]. Preparation and characterisation of MgCS, a compound containing magnesium and chondroitin sulphate, two chemicals found to be effective in treating OA. It helps by boosting cartilage production and halting its breakdown ^[5][34]. It would appear that the delivery system’s design is not particularly straightforward. A collagen-CS-based hydrogel type distribution system was used at the outset of the study because it provides a satisfactory release profile of this bioactive agent, which is necessary to initiate osteogenesis in several clinical applications. Other protein-based drugs that target bone tissue can also be delivered using this system. The mesh worked wonderfully to hold the implant in place and stop it from moving around ^[6][35]. In order to speed up the bone healing process, orthopaedic implants were coated with cell surface bone matrix components. Type I collagen coatings on 0.8 mm titanium pins significantly improved bone remodelling during the beginning phases of fracture healing around Ti implants ^[7][36]. The Chinese sturgeon (Cart-CS) and the Russian sturgeon (Noto-CS) were used to obtain these particular lipids. Cart-CS had a higher molecular weight than Noto-CS in both sturgeon species, with the highest molecular weight found in Chinese Cart-CS. The spine and notochord of the Russian sturgeon are rich in CS-C and CS-A, and between. Natural biomolecules phenolics and biological biomaterials can be found in high concentrations in sturgeon CS. Future research will elucidate the sturgeon Cart-CS and Noto-additional CS’s functional activities ^[8][13]. When compared to a gelatin sponge, the MeCMC/CSS dressing demonstrated superior platelet adhesion. In addition, there was a high level of haemocompatibility and cytocompatibility demonstrated by the Me-CMC/CSS dressing. The findings suggest that composite dressings may be used as quick haemostatic materials ^[9][37]. Through enzymatic crosslinking, a biopolymer mimicking ECM component was prepared by incorporating bilayered calcium phosphate (BCP) nanoparticles. These findings suggest that regular member cross-linked CDTA-GTA gel with BCP nanomaterials may be useful for tissue and bone tissue engineering as a means of speeding up the bone repair process ^[10][14]. Using itaconylchondroitin sulphate nanogel (ICSNG) as a synergistic agent for reduction and stabilisation, a novel biofunctionalised nanosilver (ICS-Ag) was developed for antibacterial and anti-biofilm applications. By reducing microorganism pathogens and pathogens growth on medical equipment, ICS-Ag film has the potential to significantly enhance patient outcomes and safety ^[11][38]. The development of a nano-elemental selenium particle (chondroitin sulphate Aselenium nanoparticle, CSA-SeNP) through the membrane protein identity of Na2SeO3 and opposite charges, chondroitin sulphate A is highly promising as a selenium supplementation preparation for clinical application to tackle the challenge of healing cartilage lesions with exceptional repair effects ^[12][39]. Heparan sulphate (HS) and chondroitin sulphate (CS) play critical roles in cartilage development, cartilage development in the zebrafish pharynx, specifically the functions of heparan sulphate (HS) and chondroitin sulphate (CS) proteoglycans. Ext2 and extl3 mutants, predicted to already have defective HS polymerisation, and uxs1 and b3gat3 mutants, estimated to have cognitive impairment biosynthesis of both HS and CS due to damaged establishment of the widely known proteoglycan linkage tetrasaccharide, were examined ^[13][40]. Implantable self-crosslinking hybrid Gel-OCS/MBGN biomaterials were developed for bone repair applications. Crosslinking and gelation were both sped up by the addition of MBGNs. In comparison to Gel-CS hydrogels, Gel-OCS/MBGN hydrogels significantly enhanced the propagation and osteogenic difference of BMSCs in vitro and demonstrated efficient bone regeneration in vivo. Since the degradation and gelation behaviour of the hybrid hydrogels can be tuned, and since the hydrogels exhibit favourable mechanical behaviour and osteogenic activity ^[14][9]. Using nanostructures with novel properties and exceptional functions has the potential to improve therapeutic efficacy, and this evaluation offers a clear and onward summary of innovative theranostic nanomaterials in bone-related diseases.

The biomimetic possibility of inducing CaP precipitation by using multilayers to trap ions has potential for improving the efficiency with which biologically active fibreglass biomaterials are prepared for orthopaedic uses, such as bone tissue engineering ^[2][31]. Bone regeneration biomaterial-based structures have been developed thanks to a greater grasp of the specific activities, combined actions, and perhaps even ability to induce effects of growth factors. Bioactive agent-based strategies for modulating cell response may rely on the precise regulation of molecule release via drug delivery systems. For example, a biodegradable dosage forms system that allows for the diastolic release of PTH over the course of 21 days offers a promising alternative to the conventional, once-daily injections required to maintain therapeutic levels of this drug ^[15][41]. Applying successful methods in the lab to animal models has not always yielded the same positive results. Pilot studies can provide even a basic understanding and the in vivo performance of such techniques, leading to a more streamlined procedure for developing novel, functional tissue engineering solutions. Sulphated polysaccharides have the proper biocompatibility for osteochondral tissue engineering, and the studies discussed here show that they do not trigger any major systemic inflammation when implanted in vivo ^[16][42]. To slow the development of osteoarthritis through dual antioxidation, chondroitin sulphate MMP (ChsMA) microspheres grounded with liquiritin (LQ)-loaded liposomes (ChsMA@Lipo) were created. Enzymatic hydrolysis of ChsMA into chondroitin sulphate monomers in vivo can remove reactive oxygen species. Because of its biodegradability and dual antioxidant properties, ChsMA@Lipo holds great promise as a drug delivery platform for the treatment of osteoarthritis ^[17][43]. Numerous studies have demonstrated that chitosan’s properties are optimal for use in chondrocytes regeneration and repair when it is mixed with or covalently linked to fibroin, gelatin, collagen, or other safe man-made polymers like PEO and PCL, or when it is used as a polyelectrolyte complex with hyaluronan and chondroitin sulphate ^[18][10]. The results of this investigation suggest that a novel biocompatible selenium-chondroitin sulphate (SeCS) may be useful in the treatment of knee cartilage damage (KBD) and osteoarthritis for bone regeneration/repair applications ^[19][44]. Moreover, to aid in wound healing, the developed chitosan-HYA/nCS composite sponge can be subsumed into chitosan-HYA sponge as a transport vehicle for growth factors ^[20][45]. Chitosan and hyaluronic acid are used in wound healing, medication transport, tissue engineering, and biomedical device coatings. Besides preventing bacteria from attaching, chitosan may restore injured tissue. Natural hyaluronic acid is found in human skin, joints, and connective tissues. Medical uses include osteoarthritis, ophthalmology, cosmetic surgery, and wound healing. Patient-derived platelet-rich fibrin (PRF) and plasma (PRP) are autologous materials with high platelet concentrations ^[21][46]. Several medical specialties use PRF and PRP to speed healing and stimulate tissue regeneration ^[22][47]. Cell proliferation, angiogenesis, and tissue repair are promoted by growth factors and bioactives. Wound closure, tissue regrowth, and augmentation surgeries, orthopedics, dentistry, dermatology, and other professions now use them. PRF and PRP can improve wound healing, inflammation, and tissue regeneration when applied topically or intravenously. PRF in oral surgery speeds wound healing, bone regeneration, and extraction socket healing ^[23][48]. Although it is possible to bioprint and implant simple connective tissue in animal models, more research and optimisation are needed before complex tissues like cartilage can be printed. Although three-dimensional natural CTE frameworks have been shown to stimulate chondrogenesis in the lab, this success has not yet been transferred to clinical use [49]. ^[24]Opportunities abound for researchers in chemistry, physics, materials, engineering, physiology, and clinical medicine to work together to find lasting solutions to the pressing problems we have outlined above.

Overall, if the aforementioned obstacles can be overcome, nanomaterials may one day replace many of the conventional drugs used to treat RA ^[25][50]. The pros and cons of CS-based nanostructures for the dispatch of biopharmaceuticals, as well as stimuli-sensitive delivery systems like HAase and ROS sensitive nanocarriers for tumor-targeted delivery, are discussed in depth. The manuscript also discusses the use of CS-based tissue engineering in synthetic biology and wound healing ^[26][24]. The G10-F@Mc composite scaffold was made by loading CSA microspheres into a 3D printed framework. This scaffold has the chance of growing as a biomaterial scaffold for filling bone defects because of its ability to effectively connect the conversation of cells and considerations in bone tissue microenvironment ^[27][51]. The complex formation rather than dual modes of action on pathogenesis of degenerative cartilage may account for improvement in efficacy. These findings demonstrated the therapeutic potential of drug targeting with this ChS moving targets to articular cartilage for the treatment of OA ^[28][52]. In search of a more cost-effective and environmentally friendly source for chondroitin sulphate (CS) isolation for potential applications in tissue engineering and the pharmaceutical industry, chicken keel skeletal cartilage was investigated. Use of this technology in nanomedicine to create a reliable transportation vehicle for natural compounds, improve its specificity, and achieve controlled drug release are all potential future obstacles ^[29][53]. In general, natural polymers may help autoimmune disease patients repair their bones. They are interesting options for bone regeneration and autoimmune response management due to their flexibility, immunomodulatory effects, biodegradability, resemblance to the extracellular matrix, and biocompatibility. A microporous membrane made from a novel blend of strontium chondroitin sulphate and silk fibroin (SrCS/SF) was created. Thus, it was reasoned that the SrCS/SF membranes developed could serve as bioactive GBR membranes with multiple functions ^[30][54].

It is a clinical challenge to repair broken bones triggered by trauma, infection, tumours, or inherited conditions that cause abnormal skeletal development. Spinal fusions and osteolysis-related defects around implants also call for bone regeneration ^[31][69]. Osteoclastic resorption is the first step in bone replacement, which is quickly followed by osteoblastic formation. Frost, who coined the term “basic metabolising units”, first described the intimate relationship between resorption and formation within temporary anatomic structures (BMUs) ^[32][70]. Because the remodelling system is structured to allow for projects to be prioritised, a limited amount of effector cells can be deployed most efficiently with the most pressing needs, such as the targeted genesis of new BMUs for earlier findings repair ^[33][71]. Bone remodelling is primarily carried out by osteoclasts, osteoblasts, and osteocytes. Bone resorption is mediated by osteoclasts. They are associated to myeloid cells and developed from hematopoietic stem cells ^[34][72]. Tissue engineering scaffolds can also be made through photopolymerisation. Hydrogels of this type are typically easy to inject or print. It has been demonstrated that implantable MA-modified HA containing the small molecule drug kartogenin can gel in situ and repair cartilage defects ^[35][73]. Mitochondrial content, cellular structure, and matrix remodelling rate are all drastically different between fibrocartilage and subchondral bone. These variations in stress distribution between fibrocartilage and subchondral bone serve to safeguard cartilage in its natural state ^[36][74].

Multiple kinds of bone transplants are accessible for bone repair. Auto grafts are determined to be superior among the others due to their remarkable osteoconductive and osteogenic possibilities. Autografts have >90% effectiveness in bones defect therapy and typically 200.000 transplanted tissue are harvested in the United States alone ^[37][75]. For a self-healing structure, bone is notoriously difficult to regrow. Calcium homeostasis and stress and age-related damage repair both necessitate bone remodelling for optimal bone health. Bone is broken down by osteoclasts and rebuilt by osteoblasts. The amount of new bone formed is always exactly the same as the amount of bone resorbed, so any bone that is lost is always replaced ^[38][76]. Long bones of critical size do not unite, fusion does not occur, and there are calvarial deficiencies. Given the observation that healthy persons are incapable of self-healing lateral nodules beyond a specific threshold, it is plausible to explore the efficacy of systems for treating minor injuries by conducting experiments on rodents such as rabbits and hamsters. Many fractures can be readily repaired by utilizing sophisticated fail-safe systems that enable the examination of animals of human size through intricate models and state-of-the-art methods ^[39][77]. The study examined the accuracy and appropriateness of cone beam computed tomography (CBCT) grayscale values for evaluating radiographic bone mineral density compared to CT Hounsfield units (HU). To convert CBCT grayscale data into gold standard HU, the study determined conversion ratios and a standardised density scale resulted ^[40][78]. Bone modelling begins in the foetal stage and continues throughout life, and bone restoration is necessary for the creation and preservation of bone function. In fact, bone restoration is the process by which bone cells adapt their configuration and materials in response to mechanical stimuli. When a bone is broken, it loses its ability to support the body mechanically, prompting the body to take corrective measures ^[41][79]. Regenerating new bone and improving its basic mechanical properties through repair is an amazing process. Trauma causes damage to the skeletal and circulatory systems. A fibrin clot forms as part of the inflammatory response that kicks off the healing process after a fracture. The immune system at this point relies on “active” cells. The next step is for mesenchymal stem cells (MSCs) to migrate to the fracture site from their primary locations in the periosteum and bone marrow. Granular ECM is formed by MSCs ^[42][80]. One of the key characteristics of bone scaffolds is their capacity to endorse or intensify bone differentiation, a process that ultimately results in the generation of new mineral bone tissue. Bone extracellular matrix (ECM) synthesis and mineralisation are linked to this procedure ^[43][81]. Since rat osteogenic repair is higher than human levels, future studies using this model of osteoporosis should concentrate on animals whose bone structure is similar to that of humans. Furthermore, in order to fully understand how bone marrow-mesenchymal stem cells (BM-MSCs) repair osteoporosis, additional research is required ^[44][82]. The best way to treat osteoporosis using BM-MSCs in humans requires more clinical trials. Most of the processes involved in primary bone healing occur during bone remodelling. It is only in the later stages of secondary bone healing that the modelling and remodelling processes become active. Secondary bone healing begins with a period of reconstruction of the fracture site through intramembranous and/or endochondral ossification. Bone and cartilage are woven together to create this stability. Then, the bone undergoes a process of modelling and remodelling to restore its original shape by replacing the damaged tissue with healthy lamellar bone ^[45][83].