The effectiveness of mineralized plasmatic matrix in the closure of alveolar clefts with volumetric assessment

Objectives: The purpose of this study is to assess the effectiveness of mineralized plasmatic matrix in the soft tissue closure of naso-alveolar fistula, to estimate the postoperative bone fill and volume of the graft placed in the alveolar cleft defect using cone-beam computed tomography (CBCT) at 3rd- month and 6th- month. Material and methods: 10 patients, in the age group of 15‑30 years were included in this study. They were diagnosed with unilateral cleft lip and alveolus defects with or without a cleft palate requiring late secondary alveolar bone grafting. Alveolar cleft defects were closed with mineralized plasmatic matrix (MPM), a combination of autogenous iliac bone graft and platelet rich plasma (PRP) and platelet rich fibrin (PRF). Results: The mean defect volume pre-operatively is 0.75 cm3 and at the end of 3rd-month postoperatively is 0.51 cm3 and at 6th-month postoperatively is 0.27 cm3. The average percentage of bone fill between preoperative (A) & 3th- month postoperatively (B) is 33.4% and between 3rd-month (B) and 6th-month post operatively (C) is 49.5%. Conclusions: Utilization of this new matrix (MPM), has shown to be effective in the closure of the cleft defect, oro-nasal fistula and also reduction in the volume of the residual cleft defect seen with sequential cone-beam computed tomography (CBCT) radiographs.

Quality comparison between two different types of platelet-rich plasma for knee osteoarthritis

Introduction: Knee osteoarthritis (KOA), the most common form of osteoarthritis (OA) is a considerable health concern worldwide. Platelet-rich plasma (PRP) is a common therapeutic option for KOA. Different types of PRPs have varying efficacies. However, a comparative analysis of the qualities of these PRPs is lacking. Methods: Two types of PRPs, including autologous protein solution (APS), and leukocyte-poor PRP (LP-PRP) along with whole blood (WB) and platelet-poor plasma (PPP) were characterized for platelet content, leukocyte content, and composition in 10 healthy volunteers (HV) (the controlled laboratory study) and 16 KOA patients (a retrospective observational study). Additionally, the levels of the platelet-derived growth factor (PDGF)-BB, and different cytokines were estimated in HV. Results: In HV, the concentrations of platelets and leukocytes, levels of different cytokines, including interleukin 1 receptor antagonist (IL-1Ra), soluble TNF receptor type II (sTNF-RII), and IL-1β, and the ratio of IL-1Ra/IL-1β were significantly higher in APS, whereas the PDGF-BB was higher in LP-PRP than APS. In KOA patients, a higher concentration of platelets was observed in LP-PRP, and a higher concentration of leukocytes was observed in APS than LP-PRP. Following the PAW classification system, LP-PRP was classified as P2-B type in HV (51.3 × 104/μl) and KOA (53.4 × 104/μl), whereas APS was classified as P3-A type in HV (110.1 × 104/μl) and P2-A type in KOA (29.0 × 104/μl). In a retrospective observational study, the KOA patients who underwent APS injection had a higher incidence of arthralgia, and this arthralgia lasted for a longer time than LP-PRP injection in the same individual. Discussion: The quality of the two PRPs differed distinctively depending on their preparation methods, which might affect their clinical efficacies and adverse events. Therefore, the characterization of these parameters should be prioritized while choosing PRP.

Liver regeneration in traditional Chinese medicine: advances and challenges

Liver diseases pose a serious problem for national health care system all over the world. Liver regeneration has profound impacts on the occurrence and development of various liver diseases, and it remains an extensively studied topic. Although current knowledge has suggested two major mechanisms for liver regeneration, including compensatory hyperplasia of hepatocytes and stem or progenitor cell-mediated regeneration, the complexity of this physiopathological process determines that its effective regulation cannot be achieved by single-target or single-component approaches. Alternatively, using traditional Chinese medicine (TCM) to regulate liver regeneration is an important strategy for prevention and treatment of liver disorder and the related diseases. From the perspectives of TCM, liver regeneration can be caused by the disrupted balance between hepatic damage and regenerative capacity, and the “marrow”-based approaches have important therapeutic implications for liver regeneration. These two points have been massively supported by a number of basic studies and clinical observations during recent decades. TCM has the advantages of overall dynamic fine-tuning and early adjustment, and has exhibited enormous therapeutic benefits for various liver diseases. Here, we review the recent advances in the understanding of liver regeneration in TCM system in the hope of facilitating the application of TCM for liver diseases via regulation of liver regeneration.

Siwei Jianbu decoction improves painful paclitaxel-induced peripheral neuropathy in mouse model by modulating the NF-κB and MAPK signaling pathways

Background: Paclitaxel, a commonly used chemotherapeutic agent, is usually associated with peripheral neuropathy. Paclitaxel induced peripheral neuropathy (PIPN) can be dose limiting and may have detrimental influence on patients' quality of life. However, the mechanism of PIPN remains unclear. Medicinal herbs and their formulas might offer neuronal protection with their multitarget and integrated benefits in chemotherapy-induced peripheral neuropathy (CIPN). Siwei Jianbu decoction (J12) is a classic formula of traditional Chinese medicine which can promote blood circulation and treat diabetic nephropathy in clinical with the symptoms of weakness and pain. Methods: The effects of J12 were treated in C57BL/6 mice before injected with Paclitaxel.Behaviour studies: Measurement of mechanical hyperalgesia, thermal nociception and cold allodynia. On the last day at the end of week 6, DRGs were obtained from mice for western blot and immunohistochemical analysis containing NF-κB, p-ERK1/2 and p-SAPK/JNK protein expression. Quantitative real-time polymerase chain reaction: mRNA expression of NF-κB, IL-1β and TNF-α was analyzed. Additionally, the blood samples collected from the eye socket of the mouse were prepared to examine the levels of NF-κB, TNF-α, IL-6 and IL-1β using ELISA assay kits. Results: Hypersensitivity tests and pathology analysis have demonstrated that J12 could improve paclitaxel-induced peripheral pain. J12 acts by inhibiting the activation of (C-Jun N-terminal kinases) JNK, (extracellular signal-regulated kinase) ERK1/2 phosphorylation in (Mitogen-activated protein kinases) MAPK signaling pathway and the nuclear factor-κB (NF-κB) in C57BL/6 mice model, J12 also inhibits the production of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and IL-6. Conclusion: The present study showed that J12 ameliorates paclitaxel-induced peripheral neuropathic pain.

Matrix therapy is a cost-effective solution to reduce amputation risk and improve quality of life: pilot and case studies

Introduction: Chronic, non-healing ulcers remain one of the most challenging clinical situations for health care practitioners. Often, conventional treatments fail and lead to amputation, further decreasing the patient's quality of life and resulting in enormous medical expenditures for healthcare systems. Here we evaluated the use of and cost-effectiveness of the RGTA (ReGeneraTing Agents) medical device CACIPLIQ20 (OTR4120) for chronic lower-extremity ulcers in patients with Leriche and Fontaine Stage IV peripheral arterial disease who were not eligible for revascularization. Methods: This uncontrolled pilot study included 14 chronic lower extremity ulcers in 12 patients in one hospital. The pilot study included 12 patients with TcPO2 < 20 mm Hg and ABPI < 0.5 who had either a minimum of one chronic lower extremity ulcer or a chronic ulcer related to amputation. OTR4120 was applied twice a week or until complete healing, for up to 12 weeks. Ulcer surface area reduction (%)after 2, 4, 8 and 12 weeks, appearance after 4 weeks, and healing after 12 weeks were measured and recorded. Results: A 35% reduction in ulcer size was achieved after 4 weeks. 7 (50%) out of 14 ulcers completely healed within 1 to 3 months of treatment. Discussion: OTR4120 is an effective therapeutic option for patients with chronic lower extremity ulcers, can provide major improvement of quality of life and has the added benefit of being a significant cost-effective solution for healthcare systems.

Sonic hedgehog signaling in epithelial tissue development

The Sonic hedgehog (SHH) signaling pathway is essential for embryonic development and tissue regeneration. The dysfunction of SHH pathway is involved in a variety of diseases, including cancer, birth defects, and other diseases. Here we reviewed recent studies on main molecules involved in the SHH signaling pathway, specifically focused on their function in epithelial tissue and appendages development, including epidermis, touch dome, hair, sebaceous gland, mammary gland, tooth, nail, gastric epithelium, and intestinal epithelium. The advance in understanding the SHH signaling pathway will give us more clues to the mechanisms of tissue repair and regeneration, as well as the development of new treatment for diseases related to dysregulation of SHH signaling pathway.

Implant-type tissue-engineered cartilage derived from human auricular chondrocyte may maintain cartilaginous property even under osteoinductive condition

Introduction: There is a growing need for chondrocyte implantation for reconstructing cartilage defect. However, ossification of the implanted cartilage is a challenging problem. Implant-type tissue-engineered cartilage from human auricular chondrocytes is a three-dimensional implant type cartilage using PLLA as a scaffold for chondrocytes. Although there is a study which evaluated the ossification of this cartilage in subcutaneous area, there is no study which clarify the possibility of ossification in osteoinductive surroundings. The purpose of this study was to elucidate the possibility of the ossification of implant-type tissue-engineered cartilage using human auricular chondrocyte in an osteoinductive environment. Methods: Human chondrocytes were harvested from ear cartilage. After dispersion by enzyme digestion, they were put into either a poly-L-lactic acid (PLLA) or poly lactic-co-glycolic acid (PLGA) scaffold, with collagen gel. Implant-type tissue-engineered cartilage was interposed between pieces of human iliac bone harvested from the same donor and implanted subcutaneously in nude rats. Scaffold without chondrocytes was used as a control. After 1, 3, and 6 months, ossification and cartilage formation were evaluated by X-ray, hematoxylin-eosin (HE) stain and toluidine blue (TB) stain. Results: There was no ossification of implant-type cartilage using human chondrocytes, even under osteoinductive conditions. HE staining showed that perichondrium formed around the constructs and chondrocytes were observed 6months after the implantation. TB staining showed metachromasia in every sample, with the area of metachromasia increasing over time, suggesting maturation of the cartilage. Conclusions: In conclusion, adjacent iliac bone had no apparent effect on the maturation of cartilage in implant-type tissue-engineered cartilage. Cartilage retention and maturation even in the presence of iliac bone could have been due to a scarcity of mesenchymal stem cells in the bone and surrounding area.

Circulating CD34+ hematopoietic stem/progenitor cells paralleled with level of viremia in patients chronically infected with hepatitis B virus

Introduction: Liver regeneration is a heterogeneous process involving proliferation of different cell types in response to injury. Bone marrow derived stem cells may be involved in this process, by making contribution to parenchymal restoration and cellular replacement. We aimed to investigate the correlation between level of circulating mobilized CD34+ hematopoietic stem progenitor cells (HSPCs) and viremia level in patients chronically infected with hepatitis B virus (HBV). Methods: Blood samples were prospectively collected for assessing percentage and absolute counts of circulating CD34+ HSPCs and viral load level using flow cytometry and RT-PCR respectively. Patients with chronic hepatitis B (CHB) (n = 30), Entecavir (ETV) treated subjects (n = 30) and 20 age and gender matched healthy controls were enrolled in this study. Results were expressed as mean ± SD. Results and discussion: A significant increase in circulating CD34+ HSPCs level was observed in CHB patients (5 ± 3.1, 324 ± 195 × 103/ml) as compared to ETV treated subjects (0.57 ± 0.27,1022 ± 325) and healthy controls (0.53 ± 0.37, 694 ± 254, P < 0.001) in regards to percentage and absolute counts respectively. Levels of CD34+ HSPCs strongly and positively correlated with HBV DNA viral load levels in CHB patients (r2 = 0.8417, 0.649, P < 0.001).Thus, in chronic liver disorders (CHB), when reduced regenerative capacity of hepatocytes is reached, BMSCs mobilization occurs and their level increases in peripheral blood. The level of circulating CD34+ cells in peripheral blood of CHB patients paralleled with the hepatitis B viral load.

Experimental studies on preparation of the porous and small-diameter poly(ε-caprolactone) external vascular scaffold and its degradability and biocompatibility

Aim: This study was aim to prepare a porous poly(ε-caprolactone) (PCL) biodegradable external vascular scaffold by dipping and leaching method, and to assess its mechanical property, degradability and biocompatibility. Methods: We used the PCL-1, PCL-2 as the raw materials and NaCl particles as the pore-forming agents to construct a porous PCL external vascular scaffold. We tested the mechanical property of the porous PCL external vascular scaffold. The degradability of the scaffold was studied in the presence of thermomyces lanuginosus lipase (TL lipase). After 1, 3, and 5, 7 days, the samples were taken out, and the pH of the media was measured. The form-stability of the scaffold was investigated by macroscopic observation and the microstructure of it was observed by SEM. The cytotoxicity of the scaffold was evaluated by CCK-8 assay. Results: PCL-1 could make a white integrated external vascular scaffold with uniform texture. When the concentration of NaCl was less than or equal to 50%, the tensile strength of the porous PCL-1 external vascular scaffolds were higher than 4.2 Mpa, which meet the demand of clinical vascular transplantation. With the degradation of the scaffold in the lipase media, the form-stability of the scaffold was seriously destroyed, the surface of the scaffold began to degrade with some honeycomb holes, and the pH of the media values were lower than the initial reading of 7.4. Rat adipose-derived stem cells (rADSCs) cultured in the extractions of the porous PCL external vascular scaffold had good proliferation and cell morphology compared to the control group. Conclusion: The porous PCL-1-50 external vascular scaffold, with the 50% concentration of NaCl, had the maximum porosity on the basis of enough mechanical strength which meets the demand of clinical vascular transplantation. Moreover, it had good biocompatibility with rADSCs and the degradation mechanism of the scaffold was surface degradation.