Nanotechnology development in surgical applications: recent trends and developments

Primary joint replacement surgery is quite successful. However, it has a short lifespan. The main goal of nanotechnology in arthroplasty is to create implantable materials that can work safely and effectively while increasing the average lifespan of implants and reducing infection. A more beneficial relationship between the implant and native bone can be created by altering the fundamental surface properties of the implant (Fig. 2) [30]. To improve implant osseointegration, osteoblast function and development have been enhanced using nanotextured implant surfaces. Notably, titanium implants' biocompatibility and mechanical qualities are improved by severe plastic deformation (SPD), which reduces metal's coarse grains into the nanoscale range by subjecting the metal to a complicated high-stress condition [50]. Due to worries about possible fracture, the use of ultra-high molecular weight polyethylene (UHMWPE) implants in arthroplasty has been restricted. However, there has been a growing interest in enhancing UHMWPE's mechanical strength using nanotechnology because of its superior biocompatibility characteristics and wear resistance [51]. A new composite made by mixing in carbon nanotubes has shown translational success and may 1 day be used as the lining of an acetabulum or as a part of the tibia. Modifying an implant's surface nanostructure can improve functioning, increase implant survival, and increase resistance to static and dynamic fatigue [52].

Nanotechnology is now employed to enhance widely used bone cement, such as polymethyl methacrylate (PMMA). It is standard practice to add antibiotics to bone cement, yet it is well-known that medicines frequently last for just a short time. When added to conventional cement materials, such as polymethyl methacrylate (PMMA), nanotechnology-based antibiotic transporters such as lipid nanoparticles, silica, and clay nanotubes may improve medication delivery and enable timed release. Antimicrobial characteristics of other non-antibiotic-based nanotechnology cement additives such as chitosan, silver, and dendrimer are also being studied. Furthermore, it is well-recognized that PMMA can trigger an inflammatory response that may result in implant failure through fibrous encapsulation and inflammation [53‐56]. According to studies, adding nanostructured additives to PMMA led to higher levels of osseointegration and osteoblast activity. To enable X-ray visibility, ceramic particles such as zirconia and barium sulfate are frequently added to the cement. However, these particles have a detrimental effect on biocompatibility at the bone–implant interface. According to research by Gilliani et al. [57], these particles put into bone cement have been nanoscale modified, increasing their cytocompatibility and lowering their risk of mechanical failure. Together, these findings show the potential benefits of nanotechnology for enhancing bone cement effectiveness [57‐59].

The field of regenerative medicine has conducted substantial research on the problem of repairing cartilage deformities. Adult cartilage tissue lacks the necessary healing response for complete regeneration and, if ignored, will degenerate over time to develop osteoarthritis. Early progress has been made in preclinical attempts employing nanotechnology to supplement MSC treatment (Fig. 3) by creating a biocompatible scaffold that improves native cartilage healing [60‐64]. Using pluripotent stem cells, Liu et al. [63] created a nanofibrous scaffold made of polycaprolactone and gelatin that improved articular cartilage repair and subchondral bone regeneration. According to Mahboudi et al. [60], MSC chondrogenic differentiation was significantly improved when a nanofiber-based polyethersulfone scaffold was used. In addition to the studies listed above, a broad range of alternative scaffolds, such as injectable hydrogels and materials based on peptides, are being researched to treat cartilage abnormalities. One pilot trial with 28 patients with osteochondral defects found that 70% of the lesions were fully filled 2 years after the transplant was placed. Other clinical trials have shown conflicting findings after a 3-year follow-up. More research is being done to determine the effectiveness and safety of these scaffolds. Although using nanoparticles as scaffolds for regenerative tissue engineering has been proven to alter cell adhesion, proliferation favorably, and phenotypic selection of chondrocytes, the application of nanotechnology in cartilage regeneration has not yet attained general clinical use [65‐68].

Despite recent advancements in surgical technique and post-operative care, adhesion development following tendon surgery remains a serious concern. An exciting alternative to enhance extrinsic and intrinsic tendon repair may be provided by developments in nanotechnology and medication delivery. Using hydrosol nanoparticles as drug carriers, Zhao et al. [69] created a method to enable the controlled release of mitomycin-C, a chemotherapeutic agent with the capacity to reduce post-operative adhesions. This made it possible to preserve mechanical strength equivalent to typically repaired tendons while reducing the establishment of tendon adhesion in vivo. Another development demonstrating the potential therapeutic utility of nanotechnology in tendon healing is tendon tissue engineering, specifically nanocomposite scaffolds. Several scaffolding materials are being researched. These scaffolds appear to meet the demands of regenerated tendons better than allografts, and studies have demonstrated that they increase healing and mechanical stability [69‐72]. For example, a modified silk nano scaffold created by Sharif-Aghdam et al. [73] showed superior collagen content generation and viability. In addition, Huegel et al. [70] demonstrated that autologous nano scaffolds enhanced healing and mechanical stability in rat shoulders after supraspinatus repair surgery. Although clinical trials for tendon healing utilizing nanotechnology have not yet been conducted, several research investigations employing tissue engineering methods to mimic the bone–tendon interface are in progress.

Similar to arthroplasty, orthopedic trauma research using nanotechnology is focused on enhancing implant osseointegration and encouraging healthy bone formation after a fracture or non-union therapy. Surface alterations that allow for more accurate replication of the natural bone environment than traditional implants are the key to the potential effectiveness of nanostructured implants in trauma. Many research projects aim to design a bioactive scaffold for bone regeneration that would enable quicker healing and function recovery. Numerous studies have proven the osteogenic potential of these nanomaterials, and nanofiber scaffolds have been seen to promote cell migration and development during bone mending [74‐77]. Although there has been much research into the nanostructuring of various materials, including metals, composites, polymers, and ceramics, it has not yet been applied in clinical settings due to unresolved concerns about clinical safety. By offering a viable alternative to bone allografting, and nanotechnology may also be able to assist in the management of nonunion deformities. Nanoengineered artificial bone grafts resembling natural bone structures have demonstrated pre-clinical effectiveness in increasing osteoblast adhesion and offering sufficient mechanical stability. An ultra-thin nanomaterial called nano silicates could also aid in the repair of bone deformities. When added to collagen-based hydrogels, they have shown good bone stiffness, porosity, and mineralization. The potential future use of nanomaterials in the therapeutic context is highlighted by their capacity to increase osteogenesis and improve the osseointegration of orthopedic implants [78‐80].

Orthopedic infection is still a serious issue, resulting in implant failure, delayed recovery, and further surgery. Infections are frequently caused by bacterial biofilms, which can only be effectively treated by removing the implant. Therefore, current efforts have concentrated on creating innovative nanoparticle-equipped anti-biofilm implants. For instance, a new vancomycin drug delivery system integrated into titanium femoral stems showed continuous release for up to 100 h. Over the past 10 years, orthopedics has developed a strong interest in nanophase silver, which is clinically employed in wound treatment [81, 82]. Anti-microbial nanophase silver dressings have been superior to standard dressings in preventing infections and promoting healing [83]. Compared to titanium implants that were not coated, germs were less likely to colonize covered titanium implants thanks to a silver nano powder coating created by Kose et al. [84]. Innovative research into IL-12 nanocoatings has shown promise in reducing infections caused by open fractures and may even alter immune responses to do so. Researchers recently created a titanium pedicle screw coated with silver nanoparticles, which has prevented biofilm growth on screws placed in rabbits. Overall, attempts to manage infection using nanotechnology have shown significant promise in preventing acute post-operative infections after trauma, spinal implants, and joint replacements [84‐87].

An implant is an artificial structure used to restore or stabilize bodily processes that have been destroyed. Many implants heal bone fractures and replace hip, knee, or temporomandibular joints. Problems with biocompatibility were addressed by introducing materials, such as titanium, cement, and polymers [88, 89]. The lifespan of conventional orthopedic/dental implants is constrained due to implant failure. Failure of implants can occur for various causes, including inadequate initial bone-integrating growth on the implant's surface, production of wear debris in the articulating parts of the implant, and imbalanced tension and strain on the surrounding tissues. If an implant is firmly placed into neighboring bone or implant material induces fast bone development, the failure rate may be reduced (osseointegration). Stainless steel and cobalt chrome alloys were initially the favored metallic implants for joint replacement due to their excellent mechanical qualities. However, due to these materials' high Young's moduli, stress shielding and bone resorption occurred. Since live bone needs to be subjected to some tensile pressure to remain healthy, stress-shielding should be avoided. At the tissue–implant contact, osseointegration reduces imbalances in stress and strain. Therefore, the mechanical properties of the surrounding bone tissue should match those of the implanted material [90‐92].

Numerous methods have been explored to address these problems, such as manipulating the implant's surface, which would affect how osteoblasts work [93]. This is accomplished by supersaturating the implant's surface with calcium and phosphate [94]. Another strategy is to make the implant material's surface rougher [95]. Recent research has shown that the increased surface energetics of these proteins contribute significantly to their improved adsorption and confirmation on nanophase materials, which facilitate particular osteoblast adhesion. In addition, due to the wettability and surface properties of nanophase materials being near to protein size, they change the bioactivity of proteins [47]. In addition, surface characteristics, including implant or biomaterial composition, surface treatment, roughness, immobilization of different chemical agents to the surface, and nano features on the surface modify surface wettability and impact cell behavior. New nanoscale coatings will significantly improve surgical implants' fixation, biocompatibility, and wear properties. Like cells and tissues, nano-contoured implants or scaffold surfaces in regenerative medicine can significantly positively impact the development and proliferation of cells. The characteristics of various coating materials, including metalloceramic coatings, hydroxyapatite, and nanostructured diamond coatings, have been the subject of several studies. The most effective technique for creating nanostructured diamond coatings is chemical vapor deposition, which results in surfaces with a surface roughness of only 15 nm [92, 96, 97].

NanOss™, a synthetic bone product, is made of hydroxyapatite nanocrystals, which have the strength of stainless steel and are scaled and formed, such as native bone crystals. VITOSS is an additional artificial substitute for cancellous bone transplants. Nanoparticles of -tricalcium phosphate with a diameter of around 100 nm are included in VITOSS®. Its porosity and structural design are created to imitate human cancellous bone [98, 99].

Compared to traditional tricalcium phosphate, higher porosity, and a greater surface area allow quicker and more efficient biosorption and vascular penetration. Artificial bone is a bone-like substance used in a lab for a bone transplant [100, 101]. The two main components of bone are hydroxyapatite and collagen fibers. Additionally found are keratan sulfate, lipid, and chondroitin sulfate. The material types prepared in bone grafting include minerals (hydroxyapatite) and organic polysaccharides (chitin, chitosan, alginate). Bone cement supplemented with nano clay fillers has improved mechanical qualities. Nanophase features may be seen in selenium, nanoceramics, alumina, titania, carbon, nanometals, cobalt chrome alloys, and nanocrystalline diamonds. To treat bone fractures, periprosthetic fractures during hip revision surgery, acetabular reconstruction, filling cages in spinal column surgery, osteotomies, and to repair bone abnormalities in children, bone replacement materials are employed [22, 47, 102, 103].

The gold standard method for repairing skeletal abnormalities is bone transplantation, although there are drawbacks, including morbidity and resorption. Incorporating nanosurfaces into scaffolds may improve biocompatibility and lead to fewer issues [99, 104‐107]. Nanotechnology to stimulate bone regeneration has been studied in recent years. In an experimental model, Tsukimura et al. examined the results of titanium alloy implants that had been both sandblasted and nanomodified. According to biomechanical analysis, the push-in forces for implants that had been sandblasted, alkali-treated, and heat-treated were all much higher than for implants that had merely been sandblasted. The histomorphometric study, which demonstrated increased bone-to-implant contact after implantation on the surface of the removed nanomodified implants, further supported these findings [108].

Skin defects have been treated using artificial skin. Advanced production facilities have improved aesthetic attractiveness with the availability of novel biomaterials and products that heal well. The quantity of adsorbed proteins needed for nerve repair is increased by Type I collagen scaffolds that are nanophase silver-impregnated [122, 123]. The daily practice of plastic surgery includes the use of implants and prosthetics. Breast implants used in mastectomy-related breast augmentation and reconstruction surgeries must be strong enough to endure deformation, capable of preventing the development of capsular contracture, and long-lasting [124]. The silicone breast implants silicone rubber nanocomposite shell is strengthened with nanoscale SiO₂ [125]. Surface alterations by micro/macro texturization make the surface rougher. Available surface alterations include Biocell surface, patterned surface, and Siltex texturing. Silicone implants that have been coated in halofuginone, an anti-angiogenic substance, reduce the onset of capsular contracture [126]. Nanofiber coatings on the implants deliver chemotherapy medications tailored to the tumor's precise location at the tumor site [127]. Currently used systemic chemotherapy regimens do not have any unfavorable side effects. Maxillofacial surgery and dentistry might benefit significantly from using nanotechnology in the future, thanks to its applications in nanorobotics, nanomaterials, and biotechnology [128‐130].

To cure bone deformities, hydroxyapatite nanoparticles are employed. Protein-adsorbing nanopores on the modified surfaces of nanocrystals. Small voids left in tooth sockets following extraction are filled with calcium sulfate. It supplements the more durable bone graft material and is used to treat periodontal bone abnormalities [22, 47, 102, 103].

When new technology can be swiftly and readily taught and integrated into an established practice with little disturbance, plastic surgeons tend to pay attention to it. Surgeons are anticipated to make training investments and put up with schedule disruptions if a new technology would significantly improve their surgical practice and help them compete more effectively. New biomaterials with unique features that control cell functions have been produced due to advancements in nanotechnology, providing several therapeutic advantages. The use of breast implants in cosmetic and reconstructive breast surgery frequently results in various issues, including capsular contracture, double capsules, and late seromas [7, 17, 131, 132]. The goal of reducing those difficulties has led to the development and proposal of various breast implant surfaces. Different breast implant surfaces, a sterile, non-traumatic method, precise hemostasis, and local antibacterial medicines are currently used to treat the development of capsular contracture. Although a broad agreement has not yet been established, textured surfaces are thought to reduce the occurrence of capsular contracture. The most common causes of seroma include surgical site dead space, patient BMI, micro and macro repetitive stress, the use of acellular dermal matrix, and adjuvant radiation in patients undergoing reconstructive surgery [133‐138]. By mimicking extracellular matrix topographical cues seen in the acellular dermal matrix (ADM) in synthetic implant surfaces, Kyle et al. [139] have described the production processes and attributes of breast implant surfaces based on nanotechnology. These authors claim this method may improve implant integration and function while lowering problems. In this work, a novel maskless 3D greyscale production method was used to reproduce ADM's micro- and nanoscale characteristics in polydimethylsiloxane (PDMS). Human-derived fibroblasts. Breast tissue cultures were performed on PDMS surfaces and contrasted with smooth and textured silicone implant surfaces that are readily accessible in the market. In comparison with commercially available implant surfaces, the scientists discovered that the PDMS with repeated ADM surfaces boosted cell adhesion, proliferation, and survival, as well as increased focal contact formation and disseminated fibroblast morphology. In addition, vinculin and collagen 1 were up-regulated, whereas IL8, TNFa, TGFb1, and HSP60 were down-regulated in fibroblasts on biomimetic surfaces. Similarly, Anderson et al. [140] investigated how nano topography affected cytokine production and cell shape. New functional materials could be developed as our understanding of cell interactions and organized nanoscale structures grows. These investigations highlighted the value of a unique strategy for creating functionalized biomimetic breast implant surfaces, which were shown to considerably lessen the in vitro acute foreign body response to silicone. Breast surgery may undergo significant modifications as a result of nanotechnology [126]. Chun and Webster [141] demonstrated that poor macrophage adherence and low protein absorption make nanostructured polytetrafluoroethylene (PTFE) less immunogenic in vivo. It has also been demonstrated that nanomaterials inhibit bacteria's capacity to form biofilms. Chronic biofilm-associated infection and antibiotic resistance are caused by bacterial adherence to surfaces [141, 142]. As a result, nanotechnology will offer crucial tools for creating a new class of substrates with antimicrobial qualities and for changing conventional surfaces to prevent bacterial attachment. The idea that such minute changes can have such a big impact is exciting, and the idea of nano surfaces has many applications in integrating breast implants and controlling the inflammatory response [142, 143]. These early findings also suggest that there are still a lot of unanswered concerns in the effort to integrate nanotechnology into clinical practice. The positive outcomes of in vivo studies can be regarded as a successful first step in introducing these implant surface modifications to plastic surgeons. However, conclusions regarding these new surface features' effect on implant performance for breast surgery applications will not be fully understood until long-term clinical studies are carried out [144].

Nanotechnology is a fascinating new topic that has several uses in skin regeneration [145, 146]. Due to their structural resemblance to the extracellular matrix, nanofibers have attracted particular attention in the field of skin regeneration as scaffolds for skin regeneration; a wide range of polymeric nanofibers with unique characteristics have been created and studied. Nanofibrous materials can operate as delivery systems for medicines, proteins, growth factors, and other compounds in addition to supporting tissue healing. In addition, nanofibrous materials' shape, biodegradability, and other capabilities may be tailored to certain wound-healing circumstances. At various phases of wound healing, several nanostructured drug delivery systems have been employed to enhance healing, including nanoparticles, micelles, nanoemulsions, and liposomes. These nanoscale delivery systems have shown to have several advantages for the healing process of wounds, including decreased cytotoxicity of drugs, administration of poorly water-soluble drugs, enhanced skin penetration, controlled release properties, antimicrobial activity, protection of drugs against light, temperature, enzymes, or pH degradation, stimulation of fibroblast proliferation, and decreased inflammation [147, 148].

Clinical burn and trauma wound treatment have been greatly enhanced by nanotechnology [149]. Different dressing materials are made to promote wound healing at every stage of the healing process [150]. Nanofiber scaffolds in three dimensions mimic the natural extracellular matrix (ECM) and promote host tissue regeneration [151]. For the best wound healing and tissue recovery, mechanical integrity, fluid absorption, temperature management, and gas exchange qualities are crucial. Nanofibers offer all the ideal circumstances for an ideal healing environment [22]. Several studies show that chitosan is a physiologically active dressing that affects wound treatment positively. According to reports, applying chitosan to open wounds in dogs caused exudate, which has a high growth factor activity, as well as inflammatory cell infiltration and the creation of granulation tissue accompanied by angiogenesis. Although chitosan-membrane-based wound products have been studied in laboratory animals and humans, they are still in their infancy [152, 153]. It has been proven that chitosan microspheres have potent antibacterial action against S. aurous [154]. Due to its biocompatibility, biodegradability, hemostatic activity, anti-inflectional activity, and ability to hasten wound healing, chitosan was chosen as a dressing material [155]. N-acetyl glucosamine (NAG), a key component of dermal tissue and a prerequisite for healing scar tissue, is found in chitin and chitosan [156]. Its positive surface charge makes it possible to assist cell proliferation efficiently and encourages surface-induced thrombosis and blood coagulation. With the acidic groups of the cellular components of blood, free amino groups present on the chitosan membrane surface may form polyelectrolyte complexes [157, 158].

On the other hand, synthetic polymers are more affordable than biopolymer chitosan [159]; thus, replacing them with one might reduce the cost of chitosan-based films without compromising their functioning. One of the medicinal plants in the Liliaceae family is aloe vera. Since ancient times, it has been used as a laxative to cure many illnesses, including infections and dermatological diseases. The leaves of this plant are long, meaty, and thick and have twisted sides that finish with thorns. A long-chain polysaccharide of the acetylated glucomannan kind, together with other carbohydrates, makes up most of the "gel" found inside the leaf, composed of 99% water [160].

Along with avoiding infections, it is critical to consider the cellular activities that affect the healing process, such as cell migration and proliferation, inflammation, angiogenesis, and the production of collagen and other ECM elements [161]. Growth factors are crucial to these occurrences and determine whether the healing process is successful. Thus, several studies have created electrospun nanofibers for growth factor administration [147].

Researchers are looking for nano adhesives that take advantage of the delicate structure of biological surfaces. For example, geckos can scale vertical surfaces, whether dry, wet, or dusty [162]. They have no glue residue on their feet. Instead, they can achieve this because of tiny spatula-like protrusions on their footpads. Spatulas alone are nonpolar. The adhesion of nonpolar surfaces is caused by the brief creation of transient dipoles on nearby surfaces. The van der Waals attraction is based on these transitory dipoles. Minor and transient van der Waals attraction forces exist individually. They may be helpful in "scarless" surgery, in the treatment of tissues too delicate for suture, such as conjunctival, corneal, or lens tissues, in the treatment of photodamaged skin, or in the treatment of fragile tissues in patients who are immunosuppressed (such as patients taking prednisone) [163].

Two clinical care specialties that are currently gaining from advances in nanotechnology are wound and burn treatment [164]. New dressing materials have to be created to recognize the significance of a moist wound-healing environment based on the physiology and features of wounds. The health industry has looked into and introduced newer dressing materials based on an understanding of the biology of wounds, as opposed to the passive coverings previously used, which evolved from "natural" coverings, such as feathers, lint, grease, milk, wine, mud, leaves, and other strange concoctions. The objectives of an "ideal" wound covering are actively facilitated by modern wound dressings, which deliver local and systemic growth factors (e.g., cytokines), debride vitalized tissue and debris, act as a bactericidal and bacteriostatic agent, and maintain ideal moisture and pH balance of the wound milieu (e.g., by either removing excess fluid or providing extra oxygen) [165].

Wound dressings can now have customizable characteristics because of nanotechnology [166]. Wound dressings made with nanotechnology have behavior that can be customized for each individual wound and can stop chronic wounds from becoming worse. The release of antibacterial, anti-inflammatory, and drug/growth factors (GFs) may be adjusted in nanotechnology-based wound dressings in reaction to the wound environment [167]. Lipase and protease enzymes are two examples of the secreted virulence factors that are released by pathogenic bacteria that can cause tissue damage and cell death. Nanotechnology allows for the encapsulation of antimicrobial compounds in nanocontainers, where medication release is dependent on the presence of harmful microorganisms [168]. The optimal wound dressing should be mechanically stable enough, have a nanofiber-engineered structure, absorb wound exudate, moisturize the wound milieu, enable gas exchange, and release wound-healing mediators and antibiotics as needed. In this review, we concentrate on cutting-edge wound dressing technology that applies nanotechnology and regenerative medicine ideas. Different approaches to treating wounds include nanomicrobial-based dressings, antimicrobial, immunomodulatory nanoparticles, gene-altering/extinguishing technologies, and growth-releasing nanoparticles. A double layer of high-density polyethylene mesh with a silver coating surrounds the nanoparticles and nanofibers used in wound dressing. The three materials most frequently utilized in wound dressings are electrospun nanofibers, polyurethane, and silk fibroin nanofibers [120].

A unique type of biomaterials known as nano biomaterials, which has at least one dimension in the nanoscale order, is an interface between biomaterials and nanotechnology [169]. Many biomaterials with short-term therapeutic uses are expected to be replaced in the following years by biodegradable biomaterials, which promote tissue regeneration and repair. For example, nanofibrous scaffolds have recently received much interest as skin healing scaffolds, mainly because they resemble ECM [170]. Synthetic medications, including antibiotics, anticancer medications, and analgesics, have been effectively mixed into nanofibers to create novel scaffolds and delivery systems. Even nucleic acids, peptides, and proteins are natural substances derived from plants [171]. It is possible to create nanofiber-based bioactive delivery systems using several techniques [172, 173]. The most basic of them is adding the bioactive material directly to the electrospun polymeric solution so it may be used when it is soluble. However, growth factors have been effectively encapsulated within the core of the fibers using core–shell nanofibers made by coaxial electrospinning and emulsion electrospinning, maintaining their bioactivity and continuous release. Post-treating electrospun fibers have increased the biocompatibility of the scaffold. Enzymes, adhesion molecules, and growth factors may all be immobilized to modify the surface properties of nanofibers and promote adherence and cell survival. Surface functionalization provides the benefit of modifying the surface features while keeping the mechanical qualities of the fibers and can be accomplished by plasma treatment, coating, or chemical techniques (such as hydrolysis and aminolysis). The tridimensional, highly porous structure of electrospun nanofibers acts as a barrier against microorganisms, preserving an adequate gas exchange and absorbing exudates when used as a wound dressing. Electrospun nanofibers can be loaded with a variety of bioactive compounds that can be delivered to the wound in a sustained manner. In addition, a variety of electrospun nanofiber composites with antibiotics have been created for use as wound dressings for the treatment of infected wounds. Along with avoiding infections, it is critical to consider the cellular activities that affect the healing process, such as cell migration and proliferation, inflammation, angiogenesis, and the production of collagen and other ECM elements [174‐176]. Growth factors are crucial to these occurrences and determine whether the healing process is successful. Thus, several studies have created electrospun nanofibers for growth factor administration. An electrospinning technique may be used to create wound dressings made of synthetic and natural polymers, depending on the kind of wound. To create bioactive nanofibers, natural items such as plant extracts and essential oils can be added to the electrospinning polymer solution. In this regard, Sun et al. [177] mixed two organic substances with a biodegradable polyester electrospun wound dressing. The scientists integrated the ginsenoside (Rg3) from Panax ginseng into PLGA nanofibers, who then used pressure-driven permeation to coat the mat with chitosan. Chitosan increased the hydrophilicity of the mat and kept the ginsenoside Rg3 release constant for 40 days. Experiments in vivo showed that hypertrophic scar development and healing time were sped up. Nanofibrous materials have been thoroughly investigated as medication delivery systems and scaffolds for skin regeneration [178]. Other nanostructured drug delivery mechanisms, such as nanoparticles and liposomes, have been applied to enhance various stages of wound healing [179]. Numerous cutting-edge remedies powered by nanotechnology have been developed to address particular issues with the healing of chronic wounds. For the standardization of nanotechnologies, more study is still needed before these medicines may be used in the clinic. Skin wound healing is a highly coordinated, spatiotemporally controlled process that has been preserved throughout evolution. Hemostasis, inflammation, proliferation, and remodeling occur concurrently but in succession. Targeting the intricacy of the normal wound-healing process, cell-type specificity, an abundance of regulatory molecules, as well as the pathophysiology of chronic wounds is made possible by nanotechnology-based diagnostics and therapy techniques. In addition, there is a critical need for strong, more effective therapies for chronic wounds that may address a malfunctioning healing process at several cellular levels. These results highlight the requirement for creating and using innovative, nanotechnology-driven therapeutics [177, 180‐182]. To effectively manage wound healing and reduce any potential complications that can arise during this process, nanotherapeutic techniques were developed using materials that have at least one dimension inside the nanoscale (1–100 nm), which are used in these materials. The adaptability and tunability of the nanomaterial's physicochemical features are its main benefit over its bulk equivalents (e.g., hydrophobicity, charge, size). Furthermore, nanostructures have distinctive characteristics due to the high surface area-to-volume ratio. Nanoparticles can, therefore, administer medicines in a prolonged and regulated manner, which speeds up the healing process. Nanoparticles with inherent qualities that help treat wounds and nanomaterials utilized as therapeutic agent delivery systems are the two primary kinds of nanomaterials used in wound healing [183‐187].

The definition of tissue engineering is "the application of engineering and life science principles and methods toward a fundamental understanding of structure–function relationships in normal and pathological mammalian tissues and the development of biological substitutes to restore, maintain, or improve tissue function" [188, 189]. Three elements commonly combine to create tissue-engineered products: isolated cells, an extracellular matrix, and signal molecules, such as growth factors. New possibilities for the extracellular matrix, often known as the scaffold, are made possible by nanotechnology [190‐193]. There are three primary purposes for the extracellular matrix. The first benefit is that it makes cell distribution and localization within the body easier. In addition, it creates and preserves a three-dimensional environment for the growth of new tissues with the proper structure. Third, it directs the growth of new tissues with suitable properties. The relationship between the cells and the extracellular matrix is crucial for the finished product's intended function [194]. Scaffold materials with micro- and nano-structured surfaces significantly positively impact cell adhesion and proliferation [195, 196]. To create three-dimensional constructions with the correct qualities, (nano) porosity control is crucial. In addition, the ability to adjust mechanical properties to resemble the target tissue closely increases the likelihood that tissue-engineered items will work as intended [197, 198]. The health care sector is developing extensively in tissue engineering and regenerative medicine [199].

Furthermore, practically all scientific and clinical research on structural fat grafting, which involves the transplantation of mesenchymal stem cells to treat congenital, oncological, traumatic, or cosmetic abnormalities, is carried out by plastic surgeons. By combining engineering ideas with life sciences, tissue engineering produces goods that enhance, restore, or sustain current biological systems (Fig. 5) [200‐203]. Reconstructive plastic surgery uses cartilage engineering, which has long been used in orthopedic surgery. For example, it is a well-known approach to designing auricular cartilage for ear restoration [204, 205].

In addition, sophisticated nasal restoration following cancer, trauma, or congenital deformities is also being looked into using nasal cartilage. Skin defects have traditionally been treated using artificial skin. In recent developments, a scaffold made of polylactic and polyglycolic acids embedded with different growth factors is used, enhancing skin healing. Creating these goods can provide patients with a more natural-looking appearance following reconstruction in a safe, dependable, and repeatable manner using precise production processes and innovative biomaterials [206‐208].

Engineering nano polymeric scaffolds to imitate the qualities of ECM, i.e., its fibrous nature and nanoscale features, is a crucial part of the current therapeutic drugs used in wound healing. Scaffolds are created using a variety of nanotechnology processes, including electrospinning, self-assembly, and phase separation (Fig. 6) [209]. The most popular technique for creating nanofibers is electrospinning. Electrospinning is a tried-and-true method for creating porous polymeric nanofibers, producing nano scaffolds with structural and physical characteristics similar to the ECM. PLGA/silk fibroin SF electrospun nanofibers were employed as hybrid scaffolds to encourage fibroblast adhesion and proliferation for better healing of diabetic wounds. Healing a Skin wound is a sequential and overlapping process that requires excellent spatial and temporal coordination. Proliferation, inflammation, remodeling, and hemostasis are all ongoing processes [184, 210, 211]. The wound healing method involves various cell types, such as fibroblasts, keratinocytes, immunological, endothelium, and progenitor cells. Growth factors, cytokines, and chemokines regulate several dynamic and ongoing molecular and cellular activities. The interplay between the skin and bacteria will determine how this process turns out. Cell-to-cell and cell-to-extracellular matrix (ECM) interactions are organized by the interleukin (IL) and growth factors signaling networks to heal a wound properly. Any changes to this order result in a persistent wound that never heals. The many methods for treating wounds include antimicrobial nano-based dressings, immunomodulating antimicrobial nanoparticles, gene-modifying/silencing technologies, and growth factor-releasing nanoparticles [182, 212].

Synthetic or biological tissue adhesives that rely on in situ polymerizations and crosslinking processes have arisen during the past several decades as supplementary approaches that can solve many problems related to sutures and staples, particularly in noninvasive procedures [213, 214]. However, there are certain drawbacks to the tissue adhesives currently on the market for clinical use, such as toxicity, significant swelling, inadequate strength, and a complex polymerization process [215, 216]. In addition, precise storage and preparation requirements must be met before using these polymer-based surgical materials in vivo. Recent developments in nanotechnology have impacted the area of tissue adhesives, either by providing novel functions (such as hemostatic or antibacterial qualities) or by enhancing their mechanical properties and adhesion force to neighboring tissues [217, 218]. To lower the risk of infections or bleeding after operations, nanoparticles with antibacterial and hemostatic characteristics have also been added to polymeric adhesives [219]. Therefore, it is envisaged that multifunctional tissue adhesives tailored for a particular tissue can be created by employing such nanocarriers.

The development of injectable adhesives that may crosslink in situ and produce nano topography to improve their adherence to surrounding tissues through van der Waals interaction or mechanical interlocking is one promising route for the area [220‐222]. The subject of flexible and biodegradable electronics has dramatically benefited from recent advancements in nanofabrication methods. One possible path for the future is to build innovative tissue adhesives by fusing biodegradable electronics with polymeric tissue adhesives. Such intelligent adhesives can keep an eye on the injured site's healing process and the environment for any possible infections and inflammations. Overall, it is anticipated that tissue adhesives will become more popular due to the new features introduced to them, and they will be able to replace surgical staples and sutures in various surgeries [223, 224].

Stubinger et al. performed sinus floor elevations on 20 patients using nano-structured HA-based biomaterial and discovered that the material had outstanding tissue biocompatibility. They also reported that new trabecular bone grew within 6 months without the requirement for autogenous bone. According to the results of the histologic study, the nano-enhanced biomaterial functioned as a robust osteoconductive bone replacement with no indication of an ongoing noticeable foreign body response [106]. In dentistry and among maxillofacial surgeons, bioceramics are frequently utilized to restore missing teeth, close jaw deformities, perform mandibular reconstruction, and perform temporomandibular joint surgery [225]. The scientists remark that 3D porous nano-HA scaffolds containing bone-marrow seeds displayed cell adhesion, proliferation, and differentiation, providing promise for rebuilding bony defects [226]. In addition, Nanophase HA has been shown to have better osteointegration capabilities. Better implants can be created using nanophase HA, because it more closely resembles the nanostructure of natural bones and offers the potential for stronger osteointegration, more natural mechanical qualities, less immune reaction, and better control of cell responses. The consequences of craniofacial surgery are enormous [227].

One may see a surgeon able to alter and monitor individual cells by creating a new set of tools on the nanoscale. For example, the neurosurgical elements might be highly advantageous, and the patient will also profit from the lessened trauma of even tiny incisions. The processing of microstructured hard metal with diamond coating can significantly improve the performance of surgical blades. Diamond nanolayers' minimal physical adherence to substances or tissues and chemical and biological inertness are significant benefits in this application. Diamond also has a low coefficient of friction, which lowers the required piercing force [331]. New manufacturing techniques have made it possible to produce surgical blades with cutting-edge diameters between 5 nm and 1 m. For use in ophthalmology, neurosurgery, and minimally invasive surgery, diamond scalpels with cutting edges that are only a few atoms thick (about 3 nm) have been developed. The scalpel blade is around one-thousandth the breadth of a metal blade [17, 98].

A novel method for preventing surgical infections uses silver nano-coating on sutures [332]. To efficiently control bleeding and mend injured tissues, aqueous nanoparticle solutions containing Stöber (Mesoporous) silica or iron oxide are employed for nano bridging [333, 334]. For the treatment of postoperative pain, electro-spinning drug-eluting sutures with or without bupivacaine have been created [335]. Sutures and medications such as aceclofenac or insulin release the medication gradually over time. Insulin promotes wound healing by enhancing cell migration, whereas aceclofenac inhibits epidermal hyperplasia and skin irritation [336, 337]. Antibiotic-eluting sutures reduce the risk of infection while achieving good healing qualities [338]. For eye surgery, absorbable antibiotic-eluting sutures containing poly(L-lactide), PEG, and levofloxacin are utilized successfully [338]. Using atomic force microscopy, nanoneedles are made from pyramidal silicon AFM tips using focused ion beam etching, and carbon tubes are affixed to the tips of the needles. Potentially, a nano surgeon might operate on a single cell without endangering it [339, 340].

According to Barr et al., micro- and nano-topographies impact fibroblasts and the long-term bio integration of devices, such as breast implants. They cite research showing that cell filopodia can detect "nano islands down to a size of 10 nm." The consequence is that the nanoscale design could affect how the body reacts to a breast implant and how capsular contracture eventually develops. In their investigation, Barr et al. looked at the surface architecture of the shells of five breast implant materials that have been given UK approval. They discovered a significant amount of variation in surface properties. In particular, they discovered that smooth implants had a directional "shallow, regular, 5-km period rippling pattern" that is considered to be caused by how the implants are made. This surface design is hypothesized to stimulate fibroblasts to produce capsules, which accounts for the smooth implants' increased risk of capsular contracture. Contrarily, it is believed that Biocell and Siltex surfaces with random surface characteristics 100 to 200 km deep secure implants in place and lessen contracture. In particular, they discovered that smooth implants had a directional "shallow, regular, 5-km period rippling pattern" that is considered to be caused by how the implants are made. This surface design is hypothesized to stimulate fibroblasts to produce capsules, which accounts for the smooth implants' increased risk of capsular contracture. Contrarily, it is believed that Biocell and Siltex surfaces with random surface characteristics 100 to 200 km deep secure implants in place and lessen contracture [341].

Nanoscale manufacturing advancements might increase the strength of breast implants. The silicone rubber nanocomposite used to create silicone breast implants is cross-linked and strengthened. Due to its fragility, silicone rubber must be strengthened, most frequently with nanoscale SiO₂. The shell looks to be transparent when this is done. Finally, capsular contracture continues to be one of the most common long-term problems of long-term breast implant installation despite advances and breakthroughs in implant manufacture. Surface modification of implants using antifibrotic medications, such as halofuginone, has reduced capsule formation in a rat model. Estimates place the yearly incidence of Grade 3–4 breast implant capsular contracture (i.e., needing surgical intervention) at 9–27%, or 22,000–44,000 women. These challenging operations often cost around $7500. Therefore, creating a breast implant with a lower capsular contracture profile might significantly impact how this illness develops [95, 342, 343].