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Introduction: Periodontal ligament is regenerated in association with hard tissue regeneration. Tenomodulin (Tnmd) expression has been confirmed in periodontal ligament and it reportedly inhibits angiogenesis or is involved in collagen fibril maturation. The introduction of Tnmd by gene transfection in bone tissue regeneration therapy might inhibit topical hard tissue formation and induce the formation of dense fibrous tissue. Therefore, the effect of Tnmd introduction by gene transfection technique in vitro and in vivo was investigated in this study., Methods: Osteogenesis- and chondrogenesis-related gene expression levels in osteoblastic cells (MC3T3E1) and rat bone marrow derived cells were detected using qPCR three days after gene transfection with plasmid DNA (Tnmd) using non-viral gene transfection vectors: a calcium phosphate-based gene transfection vector (CaP(Tnmd)) or a cationic polymer-based reagent (JetPEI (Tnmd)). Next, an atelocollagen scaffold with or without CaP (Tnmd) or JetPEI (Tnmd) was implanted into a rat calvaria bone defect, and the remaining bone defect volume and the tissue reaction at 28 days after surgery were evaluated., Results: Runx 2 and SP7 mRNA was reduced by JetPEI (Tnmd) in both cells, but not in CaP(Tnmd). The volume of expressed Tnmd was at 9 ng/mL in both gene transfection vector. The remaining bone defect volume of JetPEI (Tnmd) was significantly bigger than that of the other groups and CaP (EGFP), and that of CaP (Tnmd) was significantly bigger than that of CaP (EGFP)., Conclusions: Tnmd introduction treatment inhibits bone formation in artificial bone defect, however, the effect of that was dependent on non-viral gene transfection vector., Competing Interests: None., (© 2022 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Inflammatory arthritis is a major cause of disability in the elderly. This condition causes joint pain, loss of function, and deterioration of quality of life, mainly due to osteoarthritis (OA) and rheumatoid arthritis (RA). Currently, available treatment options for inflammatory arthritis include anti-inflammatory medications administered via oral, topical, or intra-articular routes, surgery, and physical rehabilitation. Novel alternative approaches to managing inflammatory arthritis, so far, remain the grand challenge owing to catastrophic financial burden and insignificant therapeutic benefit. In the view of non-targeted systemic cytotoxicity and limited bioavailability of drug therapies, a major concern is to establish stimuli-responsive drug delivery systems using nanomaterials with on-off switching potential for biomedical applications. This review summarizes the advanced applications of triggerable nanomaterials dependent on various internal stimuli (including reduction-oxidation (redox), pH, and enzymes) and external stimuli (including temperature, ultrasound (US), magnetic, photo, voltage, and mechanical friction). The review also explores the progress and challenges with the use of stimuli-responsive nanomaterials to manage inflammatory arthritis based on pathological changes, including cartilage degeneration, synovitis, and subchondral bone destruction. Exposure to appropriate stimuli induced by such histopathological alterations can trigger the release of therapeutic medications, imperative in the joint-targeted treatment of inflammatory arthritis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

For almost three decades from its discovery, amorphous calcium phosphate (ACP) was not considered a suitable biomaterial due to its structural instability. Thanks to its unique properties in respect to crystalline calcium phosphate phases, nowadays ACP is used in promising devices for hard tissue regeneration. Here we have highlighted the features of ACP that were harnessed to create excellent biomaterials for dental remineralization, self-setting bone cements, drug delivery, and coatings of prostheses. Its current limitations as well as future perspectives of development were concisely described. Despite more research works are needed, we envisage that the future of ACP is bright., Competing Interests: M.I. declares two patent filings related to some of the technologies presented in this article (WO2016012452 filed on 21/07/2015 and WO2020002517 filed on 27/06/2019). The authors declare no other conflicts of interest., (© 2021 The Author(s).)

Proteins and peptides (PPs) have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity and efficacy, but fewer side effects. Owing to the poor stability and limited permeability through gastrointestinal (GI) tract and epithelia, the therapeutic PPs are usually administered by parenteral route. Given the big demand for oral administration in clinical use, a variety of researches focused on developing new technologies to overcome GI barriers of PPs, such as enteric coating, enzyme inhibitors, permeation enhancers, nanoparticles, as well as intestinal microdevices. Some new technologies have been developed under clinical trials and even on the market. This review summarizes the history, the physiological barriers and the overcoming approaches, current clinical and preclinical technologies, and future prospects of oral delivery of PPs., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

The study aims to assess the concentration of vascular endothelial growth factors (VEGF) with platelet rich fibrin (PRF) biomaterial, while using it separately or in combination with nanohydroxyapatite (nano-HA) for treating intra-bony defects (IBDs) using radiographic evaluation (DBS-Win software). Sixty patients with IBD (one site/patient) and chronic periodontitis were recruited randomly to test either autologous PRF platelet concentrate, nano-HA bone graft, a combination of PRF platelet concentrate and nano-HA, or alone conventional open flap debridement (OFD). Recordings of clinical parameters including probing depth (PD), gingival index (GI), and clinical attachment level (CAL) were obtained at baseline and 6 months, post-operatively. One-way analysis of variance (ANOVA) was used to compare four groups; whereas, multiple comparisons were done through Tukey's post hoc test. The results showed that CAL at baseline changed from 6.67 ± 1.23 to 4.5 ± 1.42 in group I, 6.6 ± 2.51 to 4.9 ± 1.48 in group II, 5.2 ± 2.17 to 3.1 ± 1.27 in group III, and 4.7 ± 2.22 to 3.7 ± 2.35 in group IV after 6 months. The most significant increase in bone density and fill was observed for IBD depth in group III that was recorded as 62.82 ± 24.6 and 2.31 ± 0.75 mm, respectively. VEGF concentrations were significantly increased at 3, 7, and 14 days in all groups. The use of PRF with nano-HA was successful regenerative periodontal therapy to manage periodontal IBDs, unlike using PRF alone. Increase in VEGF concentrations in all group confirmed its role in angiogenesis and osteogenesis in the early stages of bone defect healing., Competing Interests: The authors declared that there is no conflict of interest., (© 2020 The Authors.)

Background: To improve tendon-to-bone healing in anterior cruciate ligament (ACL) reconstruction, a novel technique via the calcium phosphate (CaP) hybridization method for tendon graft using an alternate soaking process was developed. The use of the CaP hybridization method for quadriceps tendon-bone (QTB) graft in ACL reconstruction has not been reported in previous studies. Thus, this clinical trial aimed to clarify the safety and feasibility of using CaP hybridization method for quadriceps tendon-bone (QTB) graft in ACL reconstruction., Methods: Eight patients (average age, 41.6 ± 10.6 years; 2 men and 6 women) with unilateral ACL injury were included in this study. They underwent ACL reconstruction using QTB graft that hybridized CaP. The follow-up period was from 2 months to 4 years (average, 2.4 ± 1.5 years). Cases of adverse events, including tumor formation, infection, fracture, contracture, severe pain, and re-rupture, were recorded. Moreover, clinical results (KT-1000 arthrometry, pivot-shift test, International Knee Documentation Committee grade, Lysholm scale, and sports activity level), and images of graft and bone tunnel (magnetic resonance imaging, arthroscopic appearance, and computed tomography) were also evaluated., Results: No adverse events were observed in the follow-up periods. Postoperative clinical results showed improvement compared with the preoperative findings. The sports activity level after the surgery became equivalent to that before injury. There was no progression of bone tunnel enlargement., Conclusions: Using the CaP hybridization method for QTB graft in ACL reconstruction was safe and feasible in the clinical trial. Moreover, this method may improve clinical outcomes. In the future, it is necessary to verify the effect of the CaP hybridization method for QTB graft in ACL reconstruction.

Objectives: To review the possible causes of the high incidence of urolithiasis in the oil-rich Gulf States., Methods: Data were extracted from published reports on the incidence of urolithiasis, affluence and diet in the Gulf States, various Western countries and China., Results: There are strong relationships: (a) between the life-expectancy of stones in men and the Gross National Income (GNI) per capita of these countries; and (b) between the daily consumption of animal protein and GNI per capita. Together these data suggest that the occurrence of stones is proportional to the intake of animal protein, although they also indicate that there are additional factors that further increase the risk of urolithiasis in the populations of the Gulf. The consumption of oxalate in the Gulf is three times higher and that of calcium a half of what it is in Western countries. Thus, the average oxalate/calcium ratio in the intestines of the Gulf populations is five to six times higher than that in Western populations, leading to enteric hyperoxaluria and an increased risk of calcium-oxalate stone formation. The risk is further accentuated by the lower urine volumes, due to the hot, dry climate of the region, and lower excretions of citrate, from the highly acidic urine resulting from the high intake of animal protein. There is a high incidence of uric acid-containing stones from the acidic urine and the hyperuricosuria caused by the high intake of purine., Conclusions: The high incidence of urolithiasis in the Gulf is due to an adverse combination of dietary and environmental factors.

Objective: To compare various systems for assessing the risk of recurrent stones, based on the composition of urine., Methods: The relative supersaturation (RSS) of urine, the Tiselius Indices, the Robertson Risk Factor Algorithms (RRFA) and the BONN-Risk Index were compared in terms of the numbers of variables required to be measured, the ease of use of the system and the value of the information obtained., Results: The RSS methods require up to 14 analyses in every urine sample but measure the RSS of all the main constituents of kidney stones. The Tiselius Indices and the RRFA require only seven analyses. The Tiselius Indices yield information on the crystallisation potentials (CP) of calcium oxalate and calcium phosphate; the RRFA also provide information on the CP of uric acid. Both methods provide details on the particular urinary abnormalities that lead to the abnormal CP of that urine. The BONN-Risk Index requires two measurements in each urine sample but only provides information on the CP of calcium oxalate. Additional measurements in urine have to be made to identify the cause of any abnormality., Conclusions: The methods that are based on measuring RSS are work-intensive and unsuitable for the routine screening of patients. The Tiselius Indices and the RRFA are equally good at predicting the risk of a patient forming further stones. The BONN-Risk Index provides no additional information about the causative factors for any abnormality detected.