1.The role of crosslinked collagen-hydroxyapatite on the properties of tissue graft material.
Fitria Rahmitasari ; Widyasri Prananingrum ; Sularsih ; Moh Basroni Rizal ; Puguh Bayu Prabowo
Acta Medica Philippina 2026;60(6):99-106
OBJECTIVE
This review article aims to determine the properties, uses, toxicity, and other side effects of crosslinking agents in tissue scaffolds when applied in vitro and in vivo.
METHODSA literature search was performed using the PubMed-NCBI (MEDLINE) database (https://pubmed.ncbi.nlm. nih.gov/) with keywords: crosslinking reagent, collagen, hydroxyapatite, and bone regeneration. GRADE criteria were used to assess the quality of evidence.
RESULTSA total of six articles were included in the study. Improved mechanical properties of collagen-hydroxyapatite scaffolds with high porosity can be achieved by employing crosslinking methods, including physical dehydrothermal (DHT) treatment, chemical treatment with glutaraldehyde (GA), Microbial Transglutaminase (mTGase), 1‐ethyl‐3‐(3‐ dimethylaminopropyl) carbodiimide (EDAC), or a combination of both DHT and EDAC. Furthermore, the crosslinking of EDAC and DHT can lead to forming ester bonds between activated carboxyl groups and hydroxyl groups.
CONCLUSIONThe combination of DHT and EDAC crosslinking can increase mechanical strength, make the pore size appropriate, make the scaffold more stable, and support cell adhesion so that new cells can grow, and the process of osteogenesis can run more optimally.
Cross-linking Reagents ; Collagen ; Durapatite ; Hydroxyapatite ; Bone Regeneration
2.Role of caffeine and ethanol in modulating expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG) during orthodontic tooth movement: An in vivo study.
Ardiansyah S. Pawinru ; Eka Erwansyah ; Eddy Heriyanto Habar ; Abul Fauzi ; AMINULLAH ; Gita Gayatri ; Yustisia Puspitasari ; Ita Purnama Alwi ; Andi Husnul Hasanah
Acta Medica Philippina 2026;60(8):115-122
BACKGROUND AND OBJECTIVES
Orthodontic tooth movement is driven by bone remodeling influenced by systemic factors, including caffeine and ethanol. This study aimed to investigate the effects of caffeine and ethanol on the expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG), key bone remodeling biomarkers, during orthodontic tooth movement.
METHODSA laboratory experimental study was conducted on 30 male Wistar rats divided into three groups: K1 (orthodontic force only), K2 (force + caffeine), and K3 (force + ethanol). Orthodontic force was applied using Ni-Ti coil springs. Caffeine and ethanol were administered orally daily. On days 7 and 14, maxillary tissues were collected and analyzed via immunohistochemistry for RANK and OPG expression. Data were analyzed using One-Way ANOVA and Independent Sample T-tests with significance at pRESULTS
Caffeine and ethanol administration increased RANK and OPG expression compared to controls; however, only the ethanol group showed a significant increase in RANK expression on day 14 (p = 0.044). OPG expression was significantly higher in treatment groups at both time points (pCONCLUSION
Caffeine and ethanol modulate bone remodeling marker expression during orthodontic force application, with ethanol significantly increasing RANK expression at later stages. Further studies are needed to clarify the clinical implications for orthodontic treatment.
Animals ; Tooth Movement Techniques ; Tooth Movement ; Osteoprotegerin ; Role ; Movement ; Ethanol ; Bone Remodeling ; Caffeine ; Immunohistochemistry
3.A case of vanishing mandible: Diagnosis and treatment considerations for Gorham-Stout disease of the mandible
Harroun Valdimir T. Wong ; Johanna Patricia A. Canal
Acta Medica Philippina 2025;59(5):75-81
Gorham-Stout disease is a rare osteolytic disorder with an unclear pathophysiology. It presents as lesions characterized by the loss of the bony matrix and the proliferation of malformed vasculature. At present, there are no gold-standard diagnostic evaluation protocols and it is diagnosed through a mixture of clinical, histopathologic, and radiographic findings. We report a case of a 19-year-old female with Gorham-Stout disease presenting with an 8-year progressive soft tissue mass in the mandible. Extensive osteolysis of the mandible with clustering of the mandibular dentition is noted on computed tomography (CT) imaging. Her case was discussed in a multidisciplinary conference and her treatment was radiotherapy followed by surgery ± reconstruction. We used a CT-based three-dimensional planning technique to give 40 Gy over 20 treatment sessions to the involved areas. Post treatment, a repeat CT was done at six weeks to reassess for disease progression or stabilization, followed by surgical excision. As of 31 October 2021, no evidence of recurrence is noted 48 months after treatment. Arriving at a definitive diagnosis with GorhamStout disease is challenging and a multidisciplinary team approach can help determine the treatment choice with best outcomes.
Osteolysis, Essential ; Gorham-stout Disease
4.Research progress on enhancing osseointegration properties of polyetheretherketone implants through various modification methods.
Shilai LIU ; Xiaoke FENG ; Chunxia CHEN
Journal of Biomedical Engineering 2025;42(2):417-422
This review article summarizes the current modification methods employed to enhance the osseointegration properties of polyetheretherketone (PEEK), a novel biomaterial. Our analysis highlights that strategies such as surface treatment, surface modification, and the incorporation of bioactive composites can markedly improve the bioactivity of PEEK surfaces, thus facilitating their effective integration with bone tissue. However, to ensure widespread application of PEEK in the medical field, particularly in oral implantology, additional experiments and long-term clinical evaluations are required. Looking ahead, future research should concentrate on developing innovative modification techniques and assessment methodologies to further optimize the performance of PEEK implant materials. The ultimate goal is to provide the clinical setting with even more reliable solutions.
Benzophenones
;
Ketones/chemistry*
;
Polyethylene Glycols/chemistry*
;
Osseointegration
;
Humans
;
Polymers
;
Biocompatible Materials/chemistry*
;
Surface Properties
;
Prostheses and Implants
;
Dental Implants
5.Research progress of bioactive scaffolds in repair and regeneration of osteoporotic bone defects.
Yuangang WU ; Kaibo SUN ; Yi ZENG ; Bin SHEN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(1):100-105
OBJECTIVE:
To summarize the research progress of bioactive scaffolds in the repair and regeneration of osteoporotic bone defects.
METHODS:
Recent literature on bioactive scaffolds for the repair of osteoporotic bone defects was reviewed to summarize various types of bioactive scaffolds and their associated repair methods.
RESULTS:
The application of bioactive scaffolds provides a new idea for the repair and regeneration of osteoporotic bone defects. For example, calcium phosphate ceramics scaffolds, hydrogel scaffolds, three-dimensional (3D)-printed biological scaffolds, metal scaffolds, as well as polymer material scaffolds and bone organoids, have all demonstrated good bone repair-promoting effects. However, in the pathological bone microenvironment of osteoporosis, the function of single-material scaffolds to promote bone regeneration is insufficient. Therefore, the design of bioactive scaffolds must consider multiple factors, including material biocompatibility, mechanical properties, bioactivity, bone conductivity, and osteogenic induction. Furthermore, physical and chemical surface modifications, along with advanced biotechnological approaches, can help to improve the osteogenic microenvironment and promote the differentiation of bone cells.
CONCLUSION
With advancements in technology, the synergistic application of 3D bioprinting, bone organoids technologies, and advanced biotechnologies holds promise for providing more efficient bioactive scaffolds for the repair and regeneration of osteoporotic bone defects.
Humans
;
Tissue Scaffolds/chemistry*
;
Bone Regeneration
;
Osteoporosis/therapy*
;
Tissue Engineering/methods*
;
Biocompatible Materials/chemistry*
;
Printing, Three-Dimensional
;
Calcium Phosphates/chemistry*
;
Osteogenesis
;
Ceramics
;
Cell Differentiation
;
Hydrogels
;
Bioprinting
;
Bone and Bones
6.Applications and prospects of graphene and its derivatives in bone repair.
Zhipo DU ; Yizhan MA ; Cunyang WANG ; Ruihong ZHANG ; Xiaoming LI
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(1):106-117
OBJECTIVE:
To summarize the latest research progress of graphene and its derivatives (GDs) in bone repair.
METHODS:
The relevant research literature at home and abroad in recent years was extensively accessed. The properties of GDs in bone repair materials, including mechanical properties, electrical conductivity, and antibacterial properties, were systematically summarized, and the unique advantages of GDs in material preparation, functionalization, and application, as well as the contributions and challenges to bone tissue engineering, were discussed.
RESULTS:
The application of GDs in bone repair materials has broad prospects, and the functionalization and modification technology effectively improve the osteogenic activity and material properties of GDs. GDs can induce osteogenic differentiation of stem cells through specific signaling pathways and promote osteogenic activity through immunomodulatory mechanisms. In addition, the parameters of GDs have significant effects on the cytotoxicity and degradation behavior.
CONCLUSION
GDs has great potential in the field of bone repair because of its excellent physical and chemical properties and biological properties. However, the cytotoxicity, biodegradability, and functionalization strategies of GDs still need to be further studied in order to achieve a wider application in the field of bone tissue engineering.
Graphite/pharmacology*
;
Tissue Engineering/methods*
;
Humans
;
Osteogenesis/drug effects*
;
Biocompatible Materials/pharmacology*
;
Bone Regeneration
;
Tissue Scaffolds/chemistry*
;
Cell Differentiation
;
Bone and Bones
;
Bone Substitutes/chemistry*
;
Animals
7.Research progress on strontium modified β-tricalcium phosphate composite biomaterials with immune regulatory properties.
Huanxi LI ; Xingyu SHAN ; Hongda WANG ; Zhimin TIAN ; Chunnuo HE ; Haoqiang ZHANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(4):511-517
OBJECTIVE:
To review the research progress of strontium (Sr) modified β-tricalcium phosphate composite biomaterials (SrTCP) promoting osteogenesis through immune regulation, and provides reference and theoretical support for the further development and research of SrTCP bone repair materials in bone tissue engineering in the future.
METHODS:
The literature about SrTCP promoting osteogenesis through immune regulation at home and abroad in recent years was extensively reviewed, and the preparation methods, immune mechanism and application of promoting osteogenesis were summarized and analyzed.
RESULTS:
The preparation methods of SrTCP include solid-state reaction sintering method, solution combustion quenching method, direct doping method, ion substitution method, etc. SrTCP has immune regulatory effects, which can play an immune regulatory role in inducing macrophage polarization, inducing angiogenesis and anti oxidative stress to promote osteogenesis.
CONCLUSION
At present, studies have shown that SrTCP can promote bone defect repair through immune regulation. Subsequent studies can start from the control of the optimal repair concentration and release rate of Sr, and further clarify the specific mechanism of SrTCP in promoting angiogenesis and anti oxidative stress, which is helpful to develop new materials for bone defect repair.
Calcium Phosphates/pharmacology*
;
Strontium/pharmacology*
;
Biocompatible Materials/pharmacology*
;
Humans
;
Osteogenesis/drug effects*
;
Tissue Engineering/methods*
;
Bone Substitutes/pharmacology*
;
Bone Regeneration/drug effects*
;
Animals
;
Tissue Scaffolds/chemistry*
;
Neovascularization, Physiologic/drug effects*
;
Macrophages/immunology*
8.Effect of stretch on taurine upregulated gene 1-mediated miR-545-3p/cannbinoida receptor 2 pathway regulating distraction osteogenesis in rats.
Mengzhu ZHANG ; Bin WANG ; Zixin WANG ; Yalong WU ; Yongxin ZHENG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(5):598-604
OBJECTIVE:
To investigate the effect of stretch on long non-coding RNA taurine upregulated gene 1 (TUG1)-mediated miR-545-3p/cannbinoida receptor 2 (CNR2) pathway regulating bone regeneration in the distraction area of rats during distraction osteogenesis.
METHODS:
Thirty-six 10-week-old male Sprague Dawley rats were randomly divided into 3 groups ( n=12 in each group): group A (femoral fracture+injection of interfering RNA), group B (distraction osteogenesis+injection of interfering RNA), and group C (distraction osteogenesis+injection of TUG1). Groups A and B were injected with 60 μg of interfering RNA at the beginning of incubation period (immediate after operation), the beginning of distraction phase (7 days after operation), and the end of distraction phase (21 days after operation), and group C was injected with 60 μg of synthetic TUG1 in vivo interfering sequence at the same time. The general situation of rats in each group was observed during the experiment. The mineralization of fracture space or distraction area was observed by X-ray films at 21, 35, and 49 days after operation. At 49 days after operation, the samples of the distraction area were taken for HE staining to observe the mineralization, and real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expressions of osteoblast-related genes such as TUG1, miR-545-3p, CNR2, alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Blood samples were collected from the abdominal aorta of the rats, and the expressions of ALP and C terminal telopeptide of type Ⅰ (CTX-Ⅰ) protein were detected by ELISA assay.
RESULTS:
The results of X-ray film and HE staining observations showed that osteogenesis in group C was superior to groups A and B at the same time point. The results of qRT-PCR showed that the relative mRNA expressions of TUG1, CNR2, ALP, OCN, and OPN in group C were significantly higher than those in group A and group B, and the relative mRNA expression of miR-545-3p in group C was significantly lower than that in group A and group B ( P<0.05). The relative mRNA expressions of TUG1 and ALP in group B were significantly higher than those in group A, and the relative mRNA expression of miR-545-3p in group B was significantly lower than that in group A ( P<0.05). There was no significant difference in the relative mRNA expressions of CNR2, OCN, and OPN between group A and group B ( P>0.05). The results of ELISA showed that the expressions of ALP and CTX-Ⅰ protein were significantly higher in group C than in group A and group B, and in group B than in group A ( P<0.05).
CONCLUSION
Under the action of stretch, the expression of TUG1 in the femoral distraction area of rats increases, which promotes the expression of CNR2 by inhibiting the expression of miR-545-3P, which is helpful to the mineralization of the extension area and osteogenesis.
Animals
;
MicroRNAs/genetics*
;
Rats, Sprague-Dawley
;
Male
;
Osteogenesis, Distraction/methods*
;
Rats
;
RNA, Long Noncoding/metabolism*
;
Osteopontin/genetics*
;
Osteogenesis
;
Bone Regeneration
;
RNA, Small Interfering/genetics*
;
Osteocalcin/genetics*
;
Alkaline Phosphatase/metabolism*
;
Osteoblasts/cytology*
;
Signal Transduction
;
Femoral Fractures/surgery*
9.Research progress in three-dimensional-printed bone scaffolds combined with vascularized tissue flaps for segmental bone defect reconstruction.
Qida DUAN ; Hongyun SHAO ; Ning LUO ; Fuyang WANG ; Liangliang CHENG ; Jiawei YING ; Dewei ZHAO
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(5):639-646
OBJECTIVE:
To review and summarize the research progress on repairing segmental bone defects using three-dimensional (3D)-printed bone scaffolds combined with vascularized tissue flaps in recent years.
METHODS:
Relevant literature was reviewed to summarize the application of 3D printing technology in artificial bone scaffolds made from different biomaterials, as well as methods for repairing segmental bone defects by combining these scaffolds with various vascularized tissue flaps.
RESULTS:
The combination of 3D-printed artificial bone scaffolds with different vascularized tissue flaps has provided new strategies for repairing segmental bone defects. 3D-printed artificial bone scaffolds include 3D-printed polymer scaffolds, bio-ceramic scaffolds, and metal scaffolds. When these scaffolds of different materials are combined with vascularized tissue flaps ( e.g., omental flaps, fascial flaps, periosteal flaps, muscular flaps, and bone flaps), they provide blood supply to the inorganic artificial bone scaffolds. After implantation into the defect site, the scaffolds not only achieve structural filling and mechanical support for the bone defect area, but also promote osteogenesis and vascular regeneration. Additionally, the mechanical properties, porous structure, and biocompatibility of the 3D-printed scaffold materials are key factors influencing their osteogenic efficiency. Furthermore, loading the scaffolds with active components such as osteogenic cells and growth factors can synergistically enhance bone defect healing and vascularization processes.
CONCLUSION
The repair of segmental bone defects using 3D-printed artificial bone scaffolds combined with vascularized tissue flap transplantation integrates material science technologies with surgical therapeutic approaches, which will significantly improve the clinical treatment outcomes of segmental bone defect repair.
Printing, Three-Dimensional
;
Tissue Scaffolds
;
Humans
;
Surgical Flaps/blood supply*
;
Tissue Engineering/methods*
;
Plastic Surgery Procedures/methods*
;
Bone and Bones/surgery*
;
Biocompatible Materials
;
Bone Regeneration
;
Bone Transplantation/methods*
;
Bone Substitutes
;
Osteogenesis
10.Adhesive and injectable hydrogel microspheres for NRF2-mediated periodontal bone regeneration.
Yu WANG ; Shanshan JIN ; Yaru GUO ; Yilong LU ; Xuliang DENG
International Journal of Oral Science 2025;17(1):7-7
Regenerating periodontal bone defect surrounding periodontal tissue is crucial for orthodontic or dental implant treatment. The declined osteogenic ability of periodontal ligament stem cells (PDLSCs) induced by inflammation stimulus contributes to reduced capacity to regenerate periodontal bone, which brings about a huge challenge for treating periodontitis. Here, inspired by the adhesive property of mussels, we have created adhesive and mineralized hydrogel microspheres loaded with traditional compound cordycepin (MMS-CY). MMS-CY could adhere to the surface of alveolar bone, then promote the migration capacity of PDLSCs and thus recruit them to inflammatory periodontal tissues. Furthermore, MMS-CY rescued the impaired osteogenesis and ligament-forming capacity of PDLSCs, which were suppressed by the inflammation stimulus. Moreover, MMS-CY also displayed the excellent inhibitory effect on the osteoclastic activity. Mechanistically, MMS-CY inhibited the premature senescence induced by the inflammation stimulus through the nuclear factor erythroid 2-related factor (NRF2) pathway and reducing the DNA injury. Utilizing in vivo rat periodontitis model, MMS-CY was demonstrated to enhance the periodontal bone regeneration by improving osteogenesis and inhibiting the osteoclastic activity. Altogether, our study indicated that the multi-pronged approach is promising to promote the periodontal bone regeneration in periodontitis condition by reducing the inflammation-induced stem cell senescence and maintaining bone homeostasis.
Animals
;
Bone Regeneration/drug effects*
;
Rats
;
Periodontal Ligament/cytology*
;
Microspheres
;
NF-E2-Related Factor 2
;
Hydrogels
;
Periodontitis/therapy*
;
Osteogenesis/drug effects*
;
Disease Models, Animal
;
Stem Cells
;
Male
;
Rats, Sprague-Dawley
;
Humans


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