Special Issue on Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery

Immunomodulation in tissue engineering involves the deliberate manipulation or regulation of the immune system's response to aid in tissue regeneration, repair, or the incorporation of engineered constructs within the body. As the immune system plays a pivotal role in the success or failure of implanted biomaterials and engineered tissues, immunomodulation is a critical aspect of tissue engineering.

This Special Issue focuses on immunomodulation and the development of smart materials, aiming to advance maxillofacial surgery and improve patient outcomes and the effectiveness of treatment. By encouraging research on materials that induce M1- or M2-type macrophages, which are crucial for tissue regeneration, this Special Issue seeks to potentially accelerate healing and reduce scarring in patients undergoing maxillofacial surgery. The issue also promotes research on guided differentiation, considering cytokines as active ingredients to further enhance tissue regeneration and repair in maxillofacial surgical procedures. Research related to 4-hexylresorcinol (4HR), an emerging material for M2 induction, is also welcomed, as it has potential to lead to the discovery of innovative materials and techniques that enhance maxillofacial surgery. The development of smart materials for the optimal delivery of active ingredients can revolutionize maxillofacial surgery by ensuring precise and targeted release of therapeutic agents, thereby increasing their effectiveness.

This Special Issue presents a total of thirteen papers (eleven research papers and two review papers) covering various aspects of immunomodulation and smart materials, including advancing maxillofacial surgery, enhancing tissue regeneration, developing guided differentiation, exploring emerging materials, and optimizing the delivery of active ingredients. These studies encompass a wide range of topics, from evaluating the effects of 4HR on cellular and animal models to the development and application of innovative materials and techniques in tissue engineering and maxillofacial surgery. Kim et al. [1] reported that 4HR increases the expression of transforming growth factor-β1 (TGF-β1) in human umbilical vein endothelial cells (HUVECs) through the upregulation of the endoplasmic reticulum stress response and histone 3 acetylation. Kim et al. [2] reported that unilateral alloplastic total joint replacement demonstrated stable and reliable clinical outcomes for both the replaced and natural joint sides over a long period of time, with no significant complications or negative impacts on the natural joint side. Chang et al. [3] reported that 4HR ointment demonstrated an antioxidant effect in damaged dental pulp by increasing antioxidant capacity and glutathione peroxidase activity, while reducing the expression of inflammatory markers such as tumor necrosis factor-α and interleukin 1β. Kim et al. [4] reported that 4HR acts as a novel class I histone deacetylase (HDAC) inhibitor, effectively reducing its expression and activity. Hong et al. [5] reported that the application of sericin combined with a gelatin sponge significantly enhanced bone regeneration in a diabetic animal model, as evidenced by increased regenerated bone volume compared to control groups. Jang et al. [6] reported that 4HR administration reduced root resorption during orthodontic tooth movement in rats, while increasing the expression levels of bone regeneration associated markers, suggesting its potential protective effect against root resorption. Kim et al. [7] demonstrated that administering 4HR elevated the expression of markers related to dental hard tissue formation and hastened the eruption rate of incisors in a rat model, suggesting its potential impact on tooth development and eruption. Cossellu et al. [8] revealed that employing a Leaf Expander for slow maxillary expansion successfully rectified transverse maxillary deficiencies, while also exerting notable indirect impacts on the mandibular arch, leading to more substantial increases in primary first and second intermolar and canine width in comparison to rapid maxillary expander treatment. Lee et al. [9] reported that this study found no significant differences in implant stability or bone-to-implant contact between UV-irradiated and non-irradiated dental implants in canine models, both in the short-term (4 weeks) and long-term (12 weeks) assessments. Jung et al. [10] reported that tooth biomaterial combined with platelet-rich fibrin (PRF) and tooth biomaterial alone led to better bone regeneration in peri-implant defects than PRF alone, as assessed by micro-CT, implant stability, and histomorphometric analysis. Kang et al. [11] reported that 4HR did not exhibit estrogen-like effects in breast cancer cells or ovariectomized rats, unlike bisphenol-A and 17-β estradiol, suggesting 4HR has a different effect than pseudo-estrogen on ERα-positive cells and estrogen-deficient rat models. Jo et al. [12] reviewed that sericin, a silk constituent, has varying molecular weight and biological activity depending on the degumming method, and its diverse applications in the biomedical field include tissue engineering, burn dressing, drug delivery, and the regeneration of bone, cartilage, and nerves. Kim and Seok [13] reviewed that 4HR is a beneficial pharmacological agent in tissue engineering, as it exhibits antimicrobial, antiseptic, anti-inflammatory, and pro-bone formation properties when incorporated with biomaterials, promoting wound healing and new bone formation.

The ultimate objective of this Special Issue was to improve the quality of life for patients with maxillofacial defects. By fostering research and innovation in immunomodulation and smart materials, this issue sought to advance the development of more effective, minimally invasive, and faster-healing treatments, ultimately improving patient outcomes and well-being. As such, continued research and collaboration in this area is highly encouraged.