Special Issue: Multifunctional Coatings in Orthopedic Implants

As technology continues to advance, implants are widely used in orthopedic surgery, such as the fixation of fractures, artificial joints, the reconstruction of the spine and the correction of skeletal deformities. There are approximately millions of patients worldwide benefiting from orthopedic implants each year. Bone has a remarkable ability to regenerate by itself, and in fracture recovery, it was previously thought that the bone could heal itself if properly fixed, but this view is now considered short-sighted. Many potential causes, such as patient characteristics, local factors, surgical manipulation and implant factors, can affect fracture healing [1]. Therefore, orthopedic implants should not be considered as a mere mechanical device that simply stabilizes or replaces the function of bones and joints; they should have a broader biological function. With the general increase in life expectancy and the appearance of some bone and joint diseases in younger patients, an increasing number of patients will outlive their implants, which places higher demands on orthopedic implants.

The implant–bone contact surface is an important interface where bacteria and cells compete to win the “race for the surface” of the implant [2]. In addition, both wear particles generated by mechanical friction and subtle movements triggered by poor implant fixation can affect the success of the implant procedure [3]. More importantly, implants as foreign bodies inevitably have chemotaxis to immune cells, altering the local immune microenvironment and thus affecting the formation of new bone or the integration with the implant [4]. Orthopedic implants are usually made of titanium, titanium alloys, stainless steel and PEEK, but their biological inertness is not conducive to sterilization, osteogenesis, or local immune modulation. Although improvements can be made with systemic drug therapy, topical treatment strategies are more favored by clinical practitioners for their targeted drug delivery, lower overall dose and mitigation of potential systemic side effects. The advent and rapid development of implant coating technology is well suited to meet this requirement. Currently, there are two main causes of implant failure, infection and aseptic loosening. Infection at the implant site is mainly due to bacteria adhering to the prosthesis surface, multiplying and forming a biofilm, while aseptic loosening may arise from poor osseointegration or aseptic inflammation occurring around the implant. Therefore, how to prevent infection and promote osseointegration are the main tasks of coating design. However, in the past, the function of the coating was mainly focused on one point, namely, antibacterial or osteointegration promotion at the expense of the other. It should be realized that achieving the long-term stability of orthopedic implants relies on both functions working together.

A solid initial connection between the implant and the bone tissue reduces mutual movement and friction, and is the basis for osseointegration [5]. Coatings such as hydrogels, foams and elastic metal structures can effectively fill the gaps between the implant and the bone tissue at the micron level [6], thus achieving the purpose mentioned above. In addition, calcium phosphate, bioactive glass, titanium dioxide nanotubes, graphene oxide, silica, etc., independently facilitate osteoinduction and bone in-growth and can also be used as a coating to modify the implant surface for enhancing the subsequent osseointegration [7,8]. Notably, these coatings can also serve as drug delivery systems, which achieve antimicrobial properties while promoting osteogenesis if loaded with antimicrobial agents (e.g., antibiotics, antimicrobial peptides, metal ions and metal compounds). This approach is a hot topic of current research and involves many creative designs. However, how to increase the loading capacity of antimicrobial agents and how to improve the release characteristics are key issues that warrant investigation. The inhibition of bacterial adhesion to implant surfaces can prevent implant infection. However, many coatings are able to limit bacteria adhesion, also making it difficult for cells to adhere, which is also detrimental to the long-term stability of implants in the body [9]. At present, some polymers that can limit bacteria adhesion are modified to promote cell adhesion, including polyethylene glycol (PEG), glucan, poly(methacrylic acid) (PMAA) and poly-L-Lysine (HBPL) [10,11]. A coating that is able to directly kill the bacteria attached to the implant surface or kill bacteria indirectly by releasing antibacterial substances into the surroundings is also a recommended strategy. Bactericidal coatings, when combined with biologically active molecules, such as the extracellular matrix, growth factors, bone morphogenetic proteins and gene fragments [6,12], can form implants with multiple functions. However, how to introduce these substances together, maintain their function and control their release will be the focus of future research. It should be highlighted that the long-term stability of implants in the body can be maintained if the drug molecules or materials, which themselves are highly capable of killing bacteria, inhibit osteoclast and promote osteogenesis, are grafted onto the surface in an appropriate way [13].

Enhancing the body’s immunity and maintaining an appropriate level of local immune response is a more recommendable way to fight bacteria than through drug molecules, as it creates a long-term, broad-spectrum defense and prevents the development of bacterial resistance [14,15]. Thus, the immunomodulatory function of implant coatings is also an effective strategy against bacteria. One approach is to kill bacteria through immune cells such as macrophages, which are attracted to the site of infection by cellular chemokines released from a coating or by the physicochemical properties of the coating [16]. However, the excessive activation of macrophages can produce an osteolytic reaction that destroys the new bone formed around the implant, which should be strongly avoided. This excessive reaction may be mediated by pathogenic bacteria or may result from a foreign body reaction and sterile inflammation caused by the implant itself or by wear particles [17]. Recent studies have further shown that the immune microenvironment also plays an important role in bone tissue formation [18], which is the theoretical basis for improving the tissue microenvironment via implant coating to promote osteogenesis. Therefore, how to coordinate the level of immune response in a way that is sufficient for antibacterial promotion but not sufficient to inhibit osteogenesis should be the focus of implant coatings in the future. Angiogenesis is another important factor that affects osseointegration. Increased vascularization not only provides more oxygen and nutrients for osteogenesis, but also brings higher levels of growth factors and signaling stimulation [19]. Some studies have prepared coatings loaded with pitavastatin, cobalt ions and miR-21, providing implants with the ability to induce angiogenesis [20,21,22]. Vascular endothelial growth factor (VEGF) itself has been reported to mediate osteoblast differentiation, and some studies have also developed implant coatings loaded with fusion peptides that mimic VEGF, simultaneously enhancing anti-infection, vascularization and osseointegration [23].

In addition to this, the demand for implants is growing dramatically in other medical specialties, such as dentistry, cardiovascular surgery and neurosurgery, where preventing implant infections is a common and constant theme. The future of implant surface coating technology as a local drug delivery strategy is highly promising. With the gradual advancement of research on implant infections, the future function of medical implant surface coatings is definitely not single and mechanical, but more intelligent and multifunctional, to fit the antimicrobial characteristics of different stages and sites, as well as other special needs.