Dental implants are a common treatment for the loss of teeth. This paper summarizes current knowledge on implant surfaces, immediate loading versus conventional loading, short implants, sinus lifting, and custom implants using three-dimensional printing. Most of the implant surface modifications showed good osseointegration results. Regarding biomolecular coatings, which have been recently developed and studied, good results were observed in animal experiments. Immediate loading had similar clinical outcomes compared to conventional loading and can be used as a successful treatment because it has the advantage of reducing treatment times and providing early function and aesthetics. Short implants showed similar clinical outcomes compared to standard implants. A variety of sinus augmentation techniques, grafting materials, and alternative techniques, such as tilted implants, zygomatic implants, and short implants, can be used. With the development of new technologies in three-dimension and computer-aided design/computer-aided manufacturing (CAD/CAM) customized implants can be used as an alternative to conventional implant designs. However, there are limitations due to the lack of long-term studies or clinical studies. A long-term clinical trial and a more predictive study are needed.

With the development of computer-aided design/computer-aided manufacturing (CAD/CAM) technology, it has been possible to reconstruct the cranio-maxillofacial defect with more accurate preoperative planning, precise patient-specific implants (PSIs), and shorter operation times. The manufacturing processes include subtractive manufacturing and additive manufacturing and should be selected in consideration of the material type, available technology, post-processing, accuracy, lead time, properties, and surface quality. Materials such as titanium, polyethylene, polyetheretherketone (PEEK), hydroxyapatite (HA), poly-DL-lactic acid (PDLLA), polylactide-co-glycolide acid (PLGA), and calcium phosphate are used. Design methods for the reconstruction of cranio-maxillofacial defects include the use of a pre-operative model printed with pre-operative data, printing a cutting guide or template after virtual surgery, a model after virtual surgery printed with reconstructed data using a mirror image, and manufacturing PSIs by directly obtaining PSI data after reconstruction using a mirror image. By selecting the appropriate design method, manufacturing process, and implant material according to the case, it is possible to obtain a more accurate surgical procedure, reduced operation time, the prevention of various complications that can occur using the traditional method, and predictive results compared to the traditional method.

Bone morphogenic protein-2/4 (BMP-2/4) is an osteoinductive protein that accelerates osteogenesis when administered to bony defects. Sericin is produced by silkworms, and has a biological activity that differs depending on the degumming method used. Our results indicated that the high molecular weight fraction of silk sericin (MW > 30 kDa) obtained via sonication had a more abundant β-sheet structure than the low molecular weight fraction. Administration of the β-sheet structure silk sericin increased BMP-2/4 expression in a dose-dependent manner in RAW264.7 cells and human monocytes. This sericin increased the expression levels of toll-like receptor (TLR)-2, TLR-3, and TLR-4 in RAW264.7 cells. Application of a TLR-2 antibody or TLR pathway blocker decreased BMP-2/4 expression following sericin administration. In the animal model, the bone volume and BMP-2/4 expression were higher in rats treated with a sericin-incorporated gelatin sponge than in rats treated with a gelatin sponge alone or a sponge-incorporated with denatured sericin. In conclusion, sericin with a more abundant β-sheet structure increased BMP-2/4 expression and bone formation better than sericin with a less abundant β-sheet structure.

Sericin is a 10-to-400 kDa hydrophilic protein with high serine content and is a silk constituent together with fibroin. It is produced in the middle silk gland of the silkworm and encoded by four sericin genes. The molecular weight of sericin and its biological activity vary depending on the extraction method employed. Its chemical structure, in terms of random coil and β-sheet conformations, also differs with the extraction method, thereby extending its applications in various fields. Sericin, which was discarded in the textile industry in the past, is being applied and developed in the biomedical field, owing to its biological properties. In particular, many studies are underway in the field of tissue engineering, evaluating its applicability in burn dressing, drug delivery, bone regeneration, cartilage regeneration, and nerve regeneration.

4-Hexyl resorcinol (4HR) is an organic compound and has been used in skin care application. 4HR is an M2-type macrophage activator and elevates vascular endothelial growth factor (VEGF) expression via the hypoxia-inducible factor (HIF)-independent pathway. As endothelial cells are important in wound healing, the human umbilical vein endothelial cells (HUVECs) were treated with 4HR, and changes in VEGF-A, -C, and transforming growth factor-β1 (TGF-β1) expression were investigated. The administration of 4HR increased the expression level of VEGF-A, -C, and TGF-β1. The application of TGF-β1 protein also increased the expression level of VEGF-A and -C. Knockdown with small interfering RNA (siRNA) targeting to TGF-β1 and the selective chemical inhibition (A83-01) to ALK5 confirmed the involvement of the TGF-β signaling pathway in the 4-HR-mediated VEGFs expression. 4HR application in a burn model of diabetic rats demonstrated an increased level of angiogenic proteins with wound healing. Compared to sericin application, the 4HR application group showed more prominent capillary regeneration. Collectively, 4HR activated TGF-β1/ALK5/VEGFs signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.