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

PURPOSE: Ultrasonography has been used increasingly in orthopaedic practice credited to its low cost, easy accessibility, non-invasiveness, reproducibility, and safety from radiation. The purpose of this study was to test the validity and efficacy of ultrasonography as an adjunct in the assessment of fracture healing in long bones treated with intramedullary interlocking devices and its predictive value in determining the need for a secondary surgical procedure. METHODS: This was a descriptive longitudinal study of 40 skeletally mature patients from November 2016 to February 2019, who sustained long bone fractures of the tibia or femur treated using intramedullary interlocking nails. Patients with comminuted and segmental fracture patterns were excluded from the study. Each patient was evaluated at 6- and 12-week post-surgery using standard orthogonal radiographs and ultrasonography to assess fracture healing. Patients were then followed up until fracture union. Quantitative data was analyzed using frequency statistics and descriptive data with inferential statistics. RESULTS: Ultrasonography predicted 87.5% union and 12.5% delayed or non-union as early as 6 weeks after surgery, while radiographs predicted 22.5% union as late as 3 months of follow-up. The sensitivity and specificity of ultrasonography in assessing fracture healing were 100% and 97.2%, respectively, with a positive predictive value of 80.0%. Vascular resistance index was less than 0.5 in all patients who developed delayed or non-union. CONCLUSION Ultrasonography is able to predict fracture outcomes much earlier than standardized radiographs with comparable sensitivity and specificity. Vascular resistance index is an objective parameter in assessing callus quality and predicting fracture outcomes.
Humans ; Fracture Fixation, Intramedullary/methods* ; Male ; Female ; Ultrasonography/methods* ; Adult ; Fracture Healing ; Tibial Fractures/diagnostic imaging* ; Middle Aged ; Femoral Fractures/diagnostic imaging* ; Longitudinal Studies ; Bone Nails ; Young Adult ; Predictive Value of Tests ; Aged ; Treatment Outcome ; Adolescent

PURPOSE: The retear rate of rotator cuff (RC) after surgery is high, and the rapid and functional enthesis regeneration remains a challenge. Whether acellular amniotic membrane (AAM) helps to promote the healing of tendon to bone and which treatment is better are both unclear. The study aims to investigate the effect of AAM on the healing of RC and the best treatment for RC repair. METHODS: Thirty-three Sprague Dawley rats underwent RC transection and repair using microsurgical techniques and were randomly divided into the suturing repair only (SRO) group (n = 11), the AAM overlaying (AOL) group (n = 11), and the AAM interposition (AIP) group (n = 11), respectively. Rats were sacrificed at 4 weeks, then examined by subsequent micro-CT, and evaluated by histologic and biomechanical tests. The statistical analyses of one-way ANOVA or Kruskal-Wallis test were performed using with SPSS 23.0. A p < 0.05 was considered a significant difference. RESULTS: AAM being intervened between tendon and bone (AIP group) or overlaid over tendon to bone junction (AOL group) in a rat model, promoted enthesis regeneration, increased new bone and cartilage generation, and improved collagen arrangement and biomechanical properties in comparison with suturing repair only (SRO group) (AOL vs. SRO, p < 0.001, p = 0.004, p = 0.003; AIP vs. SRO, p < 0.001, p < 0.001, p < 0.001). Compared with the AOL group, the AIP group had better results in micro-CT evaluation, histological score, and biomechanical testing (p = 0 0.039, p = 0.011, p = 0.003, respectively). CONCLUSION In the RC repair model, AAM enhanced regeneration of the tendon to bone junction. This regeneration was more effective when the AAM was intervened at the tendon to bone interface than overlaid above the tendon to bone junction.
Animals ; Rats, Sprague-Dawley ; Rotator Cuff Injuries/surgery* ; Amnion/transplantation* ; Rats ; Wound Healing ; Rotator Cuff/surgery* ; Male ; X-Ray Microtomography ; Tendons/surgery* ; Biomechanical Phenomena

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.
Humans ; Bone Transplantation/methods* ; Membranes, Artificial ; Bone Regeneration ; Animals

Pericytes are multifunctional mural cells that surround the abluminal wall of endothelial cells and are associated with vascular development, vascular permeability, and angiogenesis. Additionally, pericytes demonstrate stem cell-like properties and contribute to neuroinflammatory processes. Pericytes have been extensively studied in the central nervous system. However, specific mechanisms underlying its involvement in various physiological and pathological conditions, especially in erectile dysfunction (ED), remain poorly understood. Advancements in in vitro and in vitro techniques, such as single-cell RNA sequencing, are expanding our understanding of pericytes. Recent studies have shown that pericyte dysfunction is considered an important factor in the pathogenesis of vascular and neurological ED. Therefore, this study aims to analyze the specific role of pericytes in ED, focusing on diabetic and neurogenic ED. This article provides a comprehensive review of research findings on PubMed from 2000 to 2023, concerning pericyte dysfunction in the process of ED, offering valuable insights, and suggesting directions for further research.
Pericytes/physiology* ; Humans ; Male ; Penis/innervation* ; Erectile Dysfunction/physiopathology* ; Nerve Regeneration/physiology* ; Neovascularization, Physiologic/physiology* ; Animals ; Angiogenesis

Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide. Radical prostatectomy (RP) is the standard treatment for localized prostate cancer, but the procedure often results in postoperative erectile dysfunction (ED). The poor efficacy of phosphodiesterase 5 inhibitors after surgery highlights the need to develop new therapies to enhance cavernous nerve regeneration and improve the erectile function of these patients. In the present study, we aimed to examine the potential of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in preserving erectile function in cavernous nerve injury (CNI) mice. We found that HB-EGF expression was reduced significantly on the 1 st day after CNI in penile tissue. Ex vivo and in vitro studies showed that HB-EGF promotes major pelvic ganglion neurite sprouting and neuro-2a (N2a) cell migration. In vivo studies showed that exogenous HB-EGF treatment significantly restored the erectile function of CNI mice to 86.9% of sham levels. Immunofluorescence staining showed that mural and neuronal cells were preserved by inducing cell proliferation and reducing apoptosis and reactive oxygen species production. Western blot analysis showed that HB-EGF upregulated protein kinase B and extracellular signal-regulated kinase activation and neurotrophic factor expression. Overall, HB-EGF is a major promising therapeutic agent for treating ED in postoperative RP.
Animals ; Male ; Heparin-binding EGF-like Growth Factor/therapeutic use* ; Erectile Dysfunction/etiology* ; Mice ; Penis/drug effects* ; Nerve Regeneration/drug effects* ; Penile Erection/drug effects* ; Peripheral Nerve Injuries/drug therapy* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Prostatectomy/adverse effects* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism*

Scar formation is characterized by dynamic alterations in collagen secretion, which critically determine scar morphology and pathological progression. In fibroblasts, collagen secretion is initiated through the activation of cytokine- and integrin-mediated signaling pathways, which promote collagen gene transcription. The procollagen polypeptide α chains undergo extensive post-translational modifications, including hydroxylation and glycosylation, within the endoplasmic reticulum (ER), followed by folding and assembly into triple-helical procollagen. Subsequent intracellular trafficking involves the sequential transport of procollagen through the ER, Golgi apparatus, and plasma membrane, accompanied by further structural refinements prior to extracellular secretion. Once secreted, procollagen is enzymatically processed to form mature collagen fibrils, which drive scar tissue remodeling. Recent advances in elucidating regulation of collagen secretion have identified pivotal molecular targets, such as transforming growth factor-beta 1 (TGF-β1), prolyl 4-hydroxylase (P4H), heat shock protein 47 (HSP47), and transport and Golgi organization protein 1 (TANGO1), providing novel therapeutic strategies to mitigate pathological scar hyperplasia and improve regenerative outcomes. This review provides a comprehensive analysis of the molecular mechanisms governing collagen secretion during scar formation, with emphasis on signaling cascades, procollagen biosynthesis, intracellular transport dynamics, and post-translational modifications, thereby offering a framework for developing targeted anti-scar therapies.
Humans ; Collagen/metabolism* ; Cicatrix/pathology* ; Signal Transduction ; Transforming Growth Factor beta1/metabolism* ; Fibroblasts/metabolism* ; Animals

OBJECTIVES: To investigate the effect of a variety of kidney-tonifying Chinese medicines on thymus regeneration after acute degeneration in mice. METHODS: Forty-eight 8-week-old male BALB/c mice were randomly divided into normal control group, model control group, negative control group, positive control group, the fructus of Cnidium monnieri (L.) Cuss. group, the fructus of Psoralea corylifolia (L.) group, the fructus of Rubus chingii Hu group, and the tuber onion seed group, with 6 mice in each group. Except for the normal control group, mice in the other groups received intraperitoneal injections of rapamycin (1 mg·kg^－1·d^－1) for 5 consecutive days followed by 14 h of starvation to induce acute thymus degeneration. After successful modeling, in treatment groups ethanol extract of the fructus of Cnidium monnieri (L.) Cuss. (0.78 g·kg^－1·d^－1), fructus of Psoralea corylifolia (L.) (0.39 g·kg^－1·d^－1), fructus of Rubus chingii Hu (0.78 g·kg^－1·d^－1) or the tuber onion seed(0.39 g·kg^－1·d^－1) was intraperitoneally injected once a day for 5 days; while the negative control group was given equal volume of normal saline, and the positive control group was given metformin (300 mg·kg^－1·d^－1). The grip strength was measured with a grip tester 2 h after the last administration. The pathological changes of thymus were observed by hematoxylin and eosin (HE) staining. The structure and distribution of thymic epithelial cells were observed by multiple immunofluorescence method. The proportion of T cell subsets in thymus and peripheral blood was analyzed by flow cytometry. The level of T cell receptor excision circles (TREC) in the genomic DNA of mouse spleen mononuclear cells was detected by quantitative polymerase chain reaction (PCR) for evaluation of thymic output function. The expression of thymus aging- and function-related factors in the thymus tissue were detected by quantitative reverse transcription PCR. The expression of cyclin-dependent kinase inhibitor 1A (p21) and tumor protein 53 (p53) were verified by immunohistochemistry. RESULTS: Rapamycin induced thymic atrophy and significantly reduced limb grip strength in mice (P<0.01). Compared with the negative control group, the limb grip strength of mice in the fructus of Psoralea corylifolia (L.) group, the fructus of Rubus chingii Hu group and the tuber onion seed group was significantly enhanced (all P<0.05), and the level of TREC in spleen of the mice in each administration group was reduced (all P<0.05). Among Chinese herb medicine-treatment groups, the recovery of thymus function and tissue structure in the tuber onion seed group was most obvious. Further study showed that compared with the negative control group, the proportion of CD4 single positive cells (CD3⁺TCR-β⁺CD4⁺CD8^－) in the thymus of the tuber onion seed group was significantly increased (P<0.01), and the proportion of CD3⁺CD28⁺ T cell and CD3⁺CD8⁺CD28⁺ T cell in peripheral blood was significantly increased (all P<0.01). The mRNA levels of IL-1α, IL-6, p21 and p53 in thymocytes were decreased (all P<0.05). The results of immunohistochemistry further confirmed the decrease in p21 and p53 expression. In normal mice, tuber onion seed was observed to enhance limb grip strength (P<0.01), while suppressing thymus output and change the distribution of T cell subsets, and there was no significant effect on thymus weight and the expression of Foxn1, SIRT1, p21, CXCL2 and PTMα. CONCLUSIONS The tuber onion seed and other kidney-tonifying traditional Chinese medicines can accelerate the regeneration process of mouse thymus after acute degeneration induced by rapamycin in mice, and the tuber onion seed exhibits the most pronounced therapeutic effect.
Animals ; Mice ; Male ; Mice, Inbred BALB C ; Thymus Gland/physiology* ; Drugs, Chinese Herbal/pharmacology* ; Sirolimus/adverse effects* ; Regeneration/drug effects*

INTRODUCTION

Epidermal inclusion cysts require surgical intervention to prevent recurrence and symptoms. Elliptical excision is definitive but results in longer scar, while minimal incision techniques offer better cosmetic outcomes despite higher recurrence rates probably due to incomplete excision. To date, there are currently no local studies published.

METHODOLOGY

A randomized controlled trial was conducted from October 2023 to May 2024 at a dermatology center in the Philippines. Patients were randomly assigned to minimal incision or elliptical excision techniques. Key metrics included operation time, scar length, post-operative complications, Hollander wound evaluation score (HWES), and histopathological completeness of excision.

RESULTS

Median operation duration was 31.86 minutes, with no significant difference between techniques (p = 0.5795). Post-operative scars were longer in the excision group (mean: 2.38 ± 0.66 cm) versus the minimal incision group (p < 0.001). Completeness of excision was higher in the excision group (83%) compared to the minimal incision group (27%) (p = 0.0123). Follow-up scar length was shorter in the minimal incision group (mean: 0.44 ± 0.21 cm) versus the excision group (mean: 2.1 ± 0.63 cm) (p < 0.001). HWES scores showed no significant difference in wound healing and aesthetic satisfaction.

CONCLUSION

Minimal incision technique results in shorter scars but lower completeness of excision compared to elliptical excision. Both techniques have similar long-term outcomes in wound healing and aesthetic satisfaction, with no recurrences or complications beyond two weeks. The choice should balance scar length and completeness of cyst removal, considering patient-specific factors.

Human ; Cicatrix ; Cysts ; Cosmetics