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.

METHODS

A 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.

RESULTS

A 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.

CONCLUSION

The 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

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.

METHODS

A 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

OBJECTIVE: Diabetes-induced gastrointestinal (GI) motility disorders are increasingly prevalent. Damage to the enteric nervous system (ENS), composed primarily of enteric neurons and glial cells, is an essential mechanism involved in these disorders. Although electroacupuncture (EA) has shown the potential to mitigate enteric neuronal loss, its mechanism is not fully understood. Additionally, the effects of EA on enteric glial cells have not been investigated. Enteric neural precursor cells (ENPCs) contribute to the structural and functional integrity of the ENS, yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored. This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved. METHODS: Transgenic mice were used to trace Nestin⁺/nerve growth factor receptor (Ngfr)⁺ ENPCs labeled with green fluorescent protein (GFP) in vivo. Mice were randomly divided into four groups: control, diabetes mellitus (DM), DM + sham EA, and DM + EA. The effects of EA on diabetic mice were evaluated by GI motility, ENS structure, and ENPC differentiation. Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms. RESULTS: EA alleviated diabetes-induced GI motility disorders, as indicated by reduced whole gut transit time, shortened colonic bead expulsion time, and enhanced smooth muscle contractility. Furthermore, EA attenuated diabetes-induced losses of enteric neurons and glial cells, thereby restoring ENS integrity. Notably, EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons. However, immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein⁺ glial cells and GFP-labeled ENPCs. Mechanistically, GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice. CONCLUSION EA facilitates ENS repair by promoting Nestin⁺/Ngfr⁺ ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling, and driving enteric gliogenesis from non-Nestin⁺/Ngfr⁺ ENPCs. These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration. Please cite this article as: Guo JL, Liu S, Ding SJ, Yang X, Du F. Electroacupuncture at ST36 improves gastrointestinal motility disorders by promoting enteric nervous system regeneration through GDNF/Ret signaling in diabetic mice. J Integr Med. 2025; 23(5):548-559.
Animals ; Electroacupuncture ; Enteric Nervous System/physiology* ; Gastrointestinal Motility/physiology* ; Glial Cell Line-Derived Neurotrophic Factor/metabolism* ; Diabetes Mellitus, Experimental/therapy* ; Signal Transduction ; Mice ; Gastrointestinal Diseases/physiopathology* ; Proto-Oncogene Proteins c-ret/metabolism* ; Mice, Transgenic ; Male ; Nerve Regeneration ; Neural Stem Cells ; Mice, Inbred C57BL ; Acupuncture Points

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

OBJECTIVE: This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age. METHODS: In total, 1,505 non-pregnant or non-lactating women (18-45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds. RESULTS: The median serum 25(OH)D was 16.63 (11.96-22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84-15.23) ng/mL], β-CTX [13.94 (12.49-15.39) ng/mL], and P1NP [13.87 (12.37-15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68-13.91) ng/mL], β-CTX [12.23 (10.22-14.23) ng/mL], and P1NP [11.85 (10.40-13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81-13.68) ng/mL], β-CTX [13.05 (11.78-14.32) ng/mL], and P1NP [12.81 (11.57-14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued. CONCLUSION In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
Humans ; Female ; Vitamin D/blood* ; Adult ; Middle Aged ; Polymorphism, Single Nucleotide ; Adolescent ; Young Adult ; China ; Biomarkers/blood* ; Bone Remodeling/genetics* ; Vitamin D-Binding Protein/genetics* ; Procollagen/blood* ; Osteocalcin/blood* ; Peptide Fragments/blood* ; East Asian People

OBJECTIVES: This study aims to evaluate the clinical effect of low-energy semiconductor laser treatment on the promotion of wound healing after maxillofacial fracture surgery. METHODS: A prospective randomized controlled study was conducted. Patients with maxillofacial fractures who were hospitalized in the Department of Trauma and Plastic Surgery, West China Hospital of Stomatology, Sichuan University, from August 2021 to June 2023 were selected as the study subjects and randomly divided into experimental and control groups. The experimental group was treated with a low-energy semiconductor laser once a day for six consecutive days after daily routine dressing change on the first day after surgery. The control group only underwent routine dressing change treatment and did not receive low-energy semiconductor laser treatment. Wound healing times, wound healing conditions, modified Stony Brook scar evaluation scale (mSBSES) scores, pain indices, and wound infection rates were compared between the two groups. RESULTS: A total of 211 patients were included in this study. A total of 104 and 107 cases comprised the experimental and control groups, respectively. A total of 128 males and 83 females were included. After low-energy semiconductor laser treatment, the facial skin wound healing time of the experimental group was found to be significantly shorter than that of the control group (P<0.05). Moreover, the wound grade A healing rate of the experimental group was higher than that of the control group on the seventh day after surgery (P<0.05). Among postoperative facial skin wound evaluation indices, the mSBSES scores of the experimental group at all observation points were higher than those of the control group (P<0.05), and the scores of the experimental group were higher than those of the control group in terms of wound width reduction, height reduction, color lightening, and incision line loss (P<0.05). In postoperative wound pain evaluation, the pain index of the experimental group after low-energy semiconductor laser treatment was significantly lower than that of the control group (P<0.05). No significant difference in wound infection rates was found between the two groups (P>0.05). CONCLUSIONS For facial skin wounds in maxillofacial fracture surgery, low-energy semiconductor laser treatment can effectively promote wound healing, improve wound healing quality, fade scars, and relieve wound pain.
Humans ; Wound Healing/radiation effects* ; Male ; Female ; Lasers, Semiconductor/therapeutic use* ; Prospective Studies ; Adult ; Middle Aged ; Low-Level Light Therapy ; Maxillofacial Injuries/surgery* ; Young Adult

OBJECTIVES: To study the clinical effect of the L-shape technique combined with concentrated growth factor on the horizontal bone defects of maxillary anterior teeth. METHODS: Twenty-five implants from 25 patients who underwent single maxillary anterior tooth implantation with simultaneous bone grafting were selected as the study subjects. Based on the bone grafting techniques, the patients were divided into a test group (L-shaped technique with guided bone regeneration combined with concentrated growth factor, 11 cases) and a control group (traditional guided bone regeneration combined with concentrated growth factor, 14 cases). The early discomfort and wound healing conditions in the two groups at two weeks after surgery were compared. The horizontal bone thickness, vertical bone thickness, and grayscale values in the augmentation area were measured immediately postsurgery and six months after surgery. Implant stability, hard tissue resorption within six months, and grayscale values were compared between the two groups. RESULTS: Differences in early discomfort, wound healing, implant stability, and grayscale values between the two groups were not statistically significant (P>0.05). Vertical bone thickness in the test group was significantly better than that in the control group at six months after surgery (P<0.05). The variation in horizontal bone thickness in the test group was significantly higher than that in the control group (P<0.05). CONCLUSIONS The application of the L-shape technique with concentrated growth factor for horizontal bone defects in the anterior maxillary area yielded satisfactory short-term results in terms of bone augmentation, early discomfort, wound healing, and implant stability at six months after surgery.
Humans ; Maxilla/diagnostic imaging* ; Intercellular Signaling Peptides and Proteins/therapeutic use* ; Wound Healing ; Bone Transplantation/methods* ; Dental Implantation, Endosseous/methods* ; Bone Regeneration ; Male ; Female ; Adult ; Dental Implants, Single-Tooth ; Middle Aged

Peri-implantitis is a pathologic condition associated with dental plaque that occurs in the implant tissue and is characterized by inflammation of the mucous membrane surrounding the implant, followed by the progressive loss of supporting bone. In this study, a case of guided bone regeneration therapy based on plaque control of peri-implant inflammation was reported. Four years after surgery for the left second premolar implant, the patient presented with "left lower posterior tooth swelling and discomfort for more than 2 years". The X-ray periapical film showed a decrease in distal bone mineral density of implant, and the clinical diagnosis was peri-implantitis of the left second premolar. Implants underwent guided bone regeneration and regular periodontal maintenance treatment. Re-examination at 3.5 months, 11 months, 18 months, and 7 years showed that the alveolar bone height and bone mineral density were stable, and the periodontal depth became shallow. However, the gingival recession was mild. In the present case, follow-up at 7 years demonstrated that the clinical periodontal indexes could be remarkably improved after complete periodontal treatment for peri-implantitis, and the alveolar bone could be well restored and regenerated.
Humans ; Peri-Implantitis/etiology* ; Follow-Up Studies ; Bone Regeneration ; Guided Tissue Regeneration, Periodontal/methods* ; Dental Plaque/prevention & control* ; Male ; Female ; Dental Implants/adverse effects*

OBJECTIVES: This study explores the differences in fluid flow within alveolar cancellous bone at various sites under orthodontic forces and elucidates the relationship between fluid shear stress and bone remodeling. These fin-dings lay the groundwork for understanding the biomechanical mechanisms of orthodontic tooth movement. METHODS: Stress relaxation tests were performed on human alveolar bone samples to determine material parameters by using the Prony series. An inverse model of alveolar bone was then developed for numerical simulations of fluid-structure interactions to calculate fluid flow within cancellous bone. Meanwhile, a rat model of tooth movement was established to investigate variations in bone remodeling speeds across different regions. RESULTS: The microstructural distribution of cancellous alveolar bone was similar in humans and rats. The bone volume fraction and trabecular thickness gradually decreased from root cervical region to root apical region, while the trabecular space gradually increased. Under the influence of orthodontic forces, fluid shear stress within cancellous bone showed spatial variability across different levels, with the highest shear stress occurring at the root apical region, ranging from 0 to 0.936 6 Pa. Additionally, the rat model of tooth movement indicated that bone remodeling occurred more rapidly at the root apical region. CONCLUSIONS Fluid stimulation has a remarkable effect on al-veolar bone remodeling, causing changes in the structure of alveolar bone and ultimately regulating the speed of structu-ral remodeling.
Bone Remodeling ; Animals ; Tooth Movement Techniques ; Rats ; Alveolar Process/physiology* ; Stress, Mechanical ; Humans ; Biomechanical Phenomena ; Cancellous Bone/physiology* ; Shear Strength

RATIONALE

Wound care practices are documented using wound registries to record wound types and characteristics, track wound status, assess impact of interventions, evaluate outcomes, and cost effectiveness. Data from wound registries may also be used for research in wound care and healthcare resource planning. However, a standardized wound registry in the Philippines is lacking, necessitating the creation and development of our own Wound Registry Form, tailored to our experience.

METHODS

This study involved the development and validation of a Wound Registry Form. An initial survey and focus group discussion with wound care practitioners were done to develop the items included in the form. The form underwent content validation with a panel of experts. Pilot data collection with 75 patients was performed to determine the interrater reliability between General Surgery (GS) and Plastic Surgery (PS) residents in a tertiary hospital when assessing patients with wounds.

RESULTS

A Wound Registry Form containing 36 variables was developed. It demonstrated a high content validity index (1.0), and good interrater reliability. The General Surgery residents and Plastic Surgery residents did not differ significantly in describing the wound, and generally agree on the choice of wound dressing, and other treatment related characteristics –such as frequency of dressing changes, antibiotic use, and septic studies done. However there was a significant difference among the two groups in two aspects –1) wound exudate consistency, with majority of GS residents rating exudates to have high viscosity, while majority of PS residents rating the exudates as of low consistency (p < 0.01), and, 2) rationale for the type of dressing use – there is a higher percentage of GS residents considering price and availability primarily, whereas PS residents tend to weigh their dressing choices on the clinical indication for it (p < 0.01). No other significant differences were observed between the two groups in terms of other parameters.

CONCLUSION

The Wound Registry Form demonstrated high content validity, and good interrater reliability. The form is a reliable data collection instrument that may be used in monitoringwound status and response to treatment, identifying trends in wound healing and management, analyzing interplay of patient and wound factors, determining effectiveness of wound care practices, and may contribute to wound care research and public health in the Philippines. Data from this tool may be used by multiple end users: by clinicians to provide evidence based wound care, by researchers who wish to explore factors contributing to the burden of wounds, by administrators who want to create an enhanced health record systems with standardized documentation of wound data, and by the public, including patients and their families, who wish to be more informed, and more proactive towards their healing.

Human ; Wounds And Injuries ; Wound Healing ; Surgery, Plastic ; General Surgery ; Exudates And Transudates ; Philippines