Multi-parameter design of triply periodic minimal surface scaffolds: from geometry optimization to biomechanical simulation.

This study introduces a multi-parameter design methodology to create triply periodic minimal surface (TPMS) scaffolds with predefined geometric characteristics. The level-set constant and unit cell lengths are systematically correlated with targeted porosity and minimum pore sizes. Network and sheet scaffolds featuring diamond, gyroid, and primitive level-set structures are generated. Three radially graded schemes are applied to each of the six scaffold type, accommodating radial variations in porosity and pore sizes. Computer simulations are conducted to assess the biomechanical performance of 18 scaffold models. Results disclose that diamond and gyroid scaffolds exhibit more expansive design ranges than primitive counterparts. While primitive scaffolds display the highest Young's modulus and permeability, their lower yield strength and mesenchymal stem cell (MSC) adhesion render them unsuitable for bone scaffolds. Gyroid scaffolds demonstrate superior mechanical and permeability performances, albeit with slightly lower MSC adhesion than diamond scaffolds. Sheet scaffolds, characterized by more uniform material distribution, exhibit superior mechanical performance in various directions, despite slightly lower permeability. The higher specific surface area of sheet scaffolds contributes to elevated MSC adhesion. The stimulus factor analysis also revealed the superior differentiation potential of sheet scaffolds over network ones. The diamond sheet type demonstrated the optimal differentiation. Introducing radial gradations enhances axial mechanical performance at the expense of radial mechanical performance. Radially decreasing porosity displays the highest permeability, MSC adhesion, and differentiation capability, aligning with the structural characteristics of human bones. This study underscores the crucial need to balance diverse biomechanical properties of TPMS scaffolds for bone tissue engineering.

A finite element study on the effects of follower load on the continuous biomechanical responses of subaxial cervical spine.

In spine biomechanics, follower loads are used to mimic the in vivo muscle forces acting on a human spine. However, the effects of the follower load on the continuous biomechanical responses of the subaxial cervical spines (C2-T1) have not been systematically clarified. This study aims at investigating the follower load effects on the continuous biomechanical responses of C2-T1. A nonlinear finite element model is reconstructed and validated for C2-T1. Six levels follower loads are considered along the follower load path that is optimized through a novel range of motion-based method. A moment up to 2 Nm is subsequently superimposed to produce motions in three anatomical planes. The continuous biomechanical responses, including the range of motion, facet joint force, intradiscal pressure and flexibility are evaluated for each motion segment. In the sagittal plane, the change of the overall range of motion arising from the follower loads is less than 6%. In the other two anatomical planes, both the magnitude and shape of the rotation-moment curves change with follower loads. At the neutral position, over 50% decrease in flexibility occurs as the follower load increases from zero to 250 N. In all three anatomical planes, over 50% and 30% decreases in flexibility occur in the first 0.5 Nm for small (≤100 N) and large (≥150 N) follower loads, respectively. Moreover, follower loads tend to increase both the facet joint forces and the intradiscal pressures. The shape of the intradiscal pressure-moment curves changes from nonlinear to roughly linear with increased follower load, especially in the coronal and transverse planes. The results obtained in this work provide a comprehensive understanding on the effects of follower load on the continuous biomechanical responses of the C2-T1.

Efficacy of bone marrow stem cells combined with core decompression in the treatment of osteonecrosis of the femoral head: A PRISMA-compliant meta-analysis.

BACKGROUND: This study used the meta-analytic approach to assess the safety and treatment efficacy of bone marrow stem cells (BMSCs) with core decompression (CD) for osteonecrosis of the femoral head (ONFH) based on randomized controlled trials (RCTs). METHODS: Electronic database of PubMed, Embase, Google Scholar, China National Knowledge Infrastructure (CNKI), and Wanfang database was searched up to December 26, 2019 for relevant RCTs about combined utilization of BMSCs and CD versus CD alone for ONFH. Gray literature sources were also searched. We conducted a meta-analysis following the guidelines of the Cochrane Reviewer's Handbook. Two independent reviewers performed the data extraction and assessed study quality. Our outcomes included the Harris hip scores (HHS) at 12 months, HHS at 24 months, necrotic area of femoral head, conversion to total hip arthroplasty (THA), visual analog pain scale at final follow-up, and adverse effects. The meta-analysis was performed with Stata 12.0. RESULTS: A total of 15 published studies with 688 patients fulfilled the requirements of inclusion criteria. Across all populations, participants in combined utilization of BMSCs group showed a statistical significance with higher HHS at 12 months (standard mean difference [SMD] 0.53, 95% confidence interval [CI] 0.29-0.77) and 24 months (SMD 0.57, 95% CI 0.36-0.77). Similarly, participants in combined utilization of BMSCs group had more advantages in reducing necrotic area of femoral head (SMD -1.05, 95% CI -1.73 to -0.38) and the rate of conversion to THA (risk ratio [RR] = 0.53, 95% CI 0.38-0.74, P = .000). No significant differences were identified regarding postoperative adverse effects postoperatively (RR = 1.03, 95% CI 0.64-1.67, P = .893). CONCLUSION: Compared with CD treated alone in the treatment of ONFH, combined utilization of CD and autologous BMSCs implantation has a better pain relief and clinical outcomes and can delay the collapse of the femoral head more effectively.

Tissue Engineering and Regenerative Medicine: Achievements, Future, and Sustainability in Asia.

Exploring innovative solutions to improve the healthcare of the aging and diseased population continues to be a global challenge. Among a number of strategies toward this goal, tissue engineering and regenerative medicine (TERM) has gradually evolved into a promising approach to meet future needs of patients. TERM has recently received increasing attention in Asia, as evidenced by the markedly increased number of researchers, publications, clinical trials, and translational products. This review aims to give a brief overview of TERM development in Asia over the last decade by highlighting some of the important advances in this field and featuring major achievements of representative research groups. The development of novel biomaterials and enabling technologies, identification of new cell sources, and applications of TERM in various tissues are briefly introduced. Finally, the achievement of TERM in Asia, including important publications, representative discoveries, clinical trials, and examples of commercial products will be introduced. Discussion on current limitations and future directions in this hot topic will also be provided.

In situ silk fibroin-mediated crystal formation of octacalcium phosphate and its application in bone repair.

The development of an ideal scaffold material is critical for the repair of bone defects. Being an important precursor of the mineralized matrix of bone tissue, octacalcium phosphate (OCP) has been considered a promising bone substitute. However, its application is largely limited due to the thermodynamical instability and poor processability of it. In this study, OCP was prepared by co-precipitation in the presence of small amount of silk fibroin (SF), which regulated the crystallization of OCP and led to the formation of SF-OCP complex. The diameters of OCP crystals in OCP, 0.1SF-OCP, 0.3SF-OCP and 1SF-OCP complexes were 489.0 ±â€¯399.1 nm, 102.2 ±â€¯50.7 nm, 94.7 ±â€¯48.4 nm and 223.7 ±â€¯167.6 nm, respectively. However, the shape of OCP crystals did not apparently change by the presence of SF. Further, porous SF/OCP composite scaffolds with pore size of 111.9 ±â€¯33.1 µm were prepared, in which small crystals of SF-OCP complex were embedded in a SF matrix. MC3T3-E1 cells could attach and proliferate well on both the rugged surfaces and the pores of SF/OCP scaffolds, indicating their decent biocompatibility. Further, SF/OCP scaffolds markedly promoted bone regeneration in a rat calvarial critical-sized defect model. Both micro-CT and H&E characterizations showed that bone formation not only occurred around the scaffolds, but also penetrated into their center. Therefore, such SF/OCP composite scaffolds may have potential applications in bone tissue engineering.

Combinations of Small RNA, RNA, and Degradome Sequencing Uncovers the Expression Pattern of microRNA⁻mRNA Pairs Adapting to Drought Stress in Leaf and Root of Dactylis glomerata L.

Drought stress is a global problem, and the lack of water is a key factor that leads to agricultural shortages. MicroRNAs play a crucial role in the plant drought stress response; however, the microRNAs and their targets involved in drought response have not been well elucidated. In the present study, we used Illumina platform (https://www.illumina.com/) and combined data from miRNA, RNA, and degradome sequencing to explore the drought- and organ-specific miRNAs in orchardgrass (Dactylis glomerata L.) leaf and root. We aimed to find potential miRNA⁻mRNA regulation patterns responding to drought conditions. In total, 519 (486 conserved and 33 novel) miRNAs were identified, of which, 41 miRNAs had significant differential expression among the comparisons (p < 0.05). We also identified 55,366 unigenes by RNA-Seq, where 12,535 unigenes were differently expressed. Finally, our degradome analysis revealed that 5950 transcripts were targeted by 487 miRNAs. A correlation analysis identified that miRNA ata-miR164c-3p and its target heat shock protein family A (HSP70) member 5 gene comp59407_c0 (BIPE3) may be essential in organ-specific plant drought stress response and/or adaptation in orchardgrass. Additionally, Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses found that "antigen processing and presentation" was the most enriched downregulated pathway in adaptation to drought conditions. Taken together, we explored the genes and miRNAs that may be involved in drought adaptation of orchardgrass and identified how they may be regulated. These results serve as a valuable genetic resource for future studies focusing on how plants adapted to drought conditions.

Proliferative Constituents from the Leaves of Micromelum integerrimum.

Two new compounds, 5-O-methyl-4-desmethyl-myricanol (1) and 6-formyl-5-isopropyl-3-hydroxymethyl-7-methyl-1H-indene (2), were isolated from the leaves of Micromelum integerrimum. Their structures were determined by spectroscopic methods. Additionally, compound 1 could stimulate the growth of NIH3T3 cells and promote cell migration. Compound 1 might exert its effects through increasing the protein expression of connective tissue growth factor.

Determination of nuclear transcription factor activity using a modified electrophoretic mobility shift assay

In this work, several major procedures of the electrophoretic mobility shift assay (EMSA) were modified including swift extraction of the nucleic protein, labeling of the probe and radioautography. The modified assay required shorter time, simplified the nucleic protein extraction, increased the radioactivity of the labeling probe, skipped the tedious process of gel drying, and produced clear images. Its results were comparable, reproducible and stable. It thus has merited for wide application.

A determinação da alteração na mobilidade eletroforética (EMSA), o método de mais ampla utilização para o estudo das interações proteínaácidos nucléicos, é tediosa e difícil de dominar. De acordo com os protocolos dacumentados e com base em nossa prática, nós modificamos os diversos processos principais dessa determinação incluindo no que diz respeito a extração de proteiínas nucleicas, marcação das provas e radioautografia. A determinação modificada requer menor tempo, simplifica a extração de ácidos nucleicos, eleva a radioatividade da prova marcada, evita o processo tedioso de secagem do gel e produz claras imagens. Seus resultados são comparáveis, reproduzíveis e estáveis, merecendo, desse modo, ampla aplicação.