The use of biomaterials and bioactive agents has shown promise in bone defect repair, leading to the development of strategies for bone regeneration. Various artificial membranes, especially collagen membranes (CMs) that are widely used for periodontal therapy and provide an extracellular matrix-simulating environment, play a significant role in promoting bone regeneration. In addition, numerous growth factors (GFs) have been used as clinical applications in regenerative therapy. However, it has been established that the unregulated administration of these factors may not work to their full regenerative potential and could also trigger unfavorable side effects. The utilization of these factors in clinical settings is still restricted due to the lack of effective delivery systems and biomaterial carriers. Hence, considering the efficiency of bone regeneration, both spaces maintained using CMs and GFs can synergistically create successful outcomes in bone tissue engineering. Therefore, recent studies have demonstrated a significant interest in the potential of combining CMs and GFs to effectively promote bone repair. This approach holds great promise and has become a focal point in our research. The purpose of this review is to highlight the role of CMs containing GFs in the regeneration of bone tissue, and to discuss their use in preclinical animal models of regeneration. Additionally, the review addresses potential concerns and suggests future research directions for growth factor therapy in the field of regenerative science.

Fibroblast growth factor-2 (FGF-2) regulates bone formation. The concept of guided bone regeneration using a resorbable collagen membrane (RCM) is generally accepted in implant dentistry. This study aimed to investigate the bone healing pattern in rat mandibular bone defects in real-time with and without RCM containing FGF-2 (RCM/FGF-2). Critical-size circular bone defects (4.0 mm diameter) were created on both sides of the rat mandibular bone. The defects were randomly divided into the following groups: control, RCM alone, RCM containing low (0.5 μg) or high (2.0 μg) concentration of FGF-2. We performed real-time in vivo micro-computerized tomography scans at the baseline and at 2, 4, and 6 weeks, and measured the volume of newly formed bone (NFB), bone mineral density (BMD) of NFB, and the closure percentage of the NFB area. At 6 weeks, the mandibular specimens were assessed histologically and histomorphometrically to evaluate the area of new bone regeneration. Real-time assessment revealed a significant increase in the volume, BMD, and closure percentage of the NFB area in the RCM/FGF-2-treated groups than that in the control and RCM groups. In the H-FGF-2 group, the volume and BMD of NFB exhibited a significant increase at 6 weeks than that at the baseline. Histological evaluation revealed the presence of osteoblasts, osteocytes, and blood vessels within the NFB. The real-time in vivo experiment demonstrated that RCM/FGF-2 effectively promoted bone regeneration within the critical-size mandibular defects in rats and verified new bone formation starting in the early postoperative phase.

Advanced glycation end-products (AGEs) are increased under hyperglycemia in vivo and are associated with the onset of diabetes. According to previous studies, AGEs exacerbate inflammatory diseases. However, the mechanism by which AGEs aggravate osteoblast inflammation remains unknown. Therefore, the aim of this study was to determine the effects of AGEs on the production of inflammatory mediators in MC3T3-E1 cells and the underlying molecular mechanisms. Co-stimulation with AGEs and lipopolysaccharide (LPS) was found to increase the mRNA and protein levels of cyclooxygenase 2 (COX2), interleukin-1α (IL-1α), S100 calcium-binding protein A9 (S100A9), and the production of prostaglandin E₂ (PGE₂) compared to no stimulation (untreated control) or individual stimulation with LPS or AGEs. In contrast, the phospholipase C (PLC) inhibitor, U73122, inhibited these stimulatory effects. Co-stimulation with AGEs and LPS also increased the nuclear translocation of nuclear factor-kappa B (NF-κB) compared to no stimulation (untreated control) or individual stimulation with LPS or AGE. However, this increase was inhibited by U73122. Co-stimulation with AGEs and LPS-induced phosphorylated phospholipase Cγ1 (p-PLCγ1) and phosphorylated c-Jun N-terminal kinase (p-JNK) expression compared to no stimulation or individual stimulation with LPS or AGEs. U73122 inhibited the effects induced by co-stimulation. siPLCγ1 did not increase the expression of p-JNK and the translocation of NF-κB. Overall, co-stimulation with AGEs and LPS may promote inflammation mediators in MC3T3-E1 cells by activating the nuclear translocation of NF-κB via PLCγ1-JNK activation.

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Background/purpose Bone morphogenetic protein-9 (BMP-9) has demonstrated multiple advantages in promoting osteogenesis. Our previous findings have indicated that the use of an absorbable collagen membrane (ACM) as a carrier for growth factors is effective in stimulating bone regeneration. The objective of this study was to assess the synergistic impact of BMP-9 incorporated into ACM (ACM/BMP-9) on bone formation within rat mandibular bone defects. Materials and methods Circular bone defects of critical size were surgically induced on both sides of the rat mandibular bone, with subsequent random allocation into distinct groups: control, ACM alone, and ACM loaded with low (0.5 μg) or high (2.0 μg) concentrations of BMP-9. We conducted real-time in vivo micro-computerized tomography scans at the baseline and at 2, 4, and 6 weeks, and measured the volume of newly formed bone (NFB), bone mineral density (BMD) of NFB, and the closure percentage of the NFB area. Histological and histomorphometric analyses were performed at 6 weeks. Results: Real-time assessment revealed notably higher levels of bone volume, BMD, and closure percentage in the NFB area for the groups treated with ACM/BMP-9 compared to the control and ACM groups. Within the high concentration of BMP-9 group, the volume and BMD of NFB exhibited a significant increase at 6 weeks compared to baseline. Histological examination confirmed the existence of osteoblasts, osteocytes, and blood vessels within the NFB. Conclusion: Considering the limitations of this research, the real-time evaluation finding indicates that ACM/BMP-9 effectively promotes bone formation in critical-size mandibular defects in rats.