Protein-spatiotemporal partition releasing gradient porous scaffolds and anti-inflammatory and antioxidant regulation remodel tissue engineered anisotropic meniscus.

Meniscus is a wedge-shaped fibrocartilaginous tissue, playing important roles in maintaining joint stability and function. Meniscus injuries are difficult to heal and frequently progress into structural breakdown, which then leads to osteoarthritis. Regeneration of heterogeneous tissue engineering meniscus (TEM) continues to be a scientific and translational challenge. The morphology, tissue architecture, mechanical strength, and functional applications of the cultivated TEMs have not been able to meet clinical needs, which may due to the negligent attention on the importance of microenvironment in vitro and in vivo. Herein, we combined the 3D (three-dimensional)-printed gradient porous scaffolds, spatiotemporal partition release of growth factors, and anti-inflammatory and anti-oxidant microenvironment regulation of Ac2-26 peptide to prepare a versatile meniscus composite scaffold with heterogeneous bionic structures, excellent biomechanical properties and anti-inflammatory and anti-oxidant effects. By observing the results of cell activity and differentiation, and biomechanics under anti-inflammatory and anti-oxidant microenvironments in vitro, we explored the effects of anti-inflammatory and anti-oxidant microenvironments on construction of regional and functional heterogeneous TEM via the growth process regulation, with a view to cultivating a high-quality of TEM from bench to bedside.

Self-Pumping Janus Hydrogel with Aligned Channels for Accelerating Diabetic Wound Healing.

Excessive exudate secreted from diabetic wounds often results in skin overhydration, severe infections, and secondary damage upon dressing changes. However, conventional wound dressings are difficult to synchronously realize the non-maceration of wound sites and rapid exudate transport due to their random porous structure. Herein, a self-pumping Janus hydrogel with aligned channels (JHA) composed of hydrophilic poly (ethylene glycol) diacrylate (PEGDA) hydrogel layer and hydrophobic polyurethane (PU)/graphene oxide (GO)/polytetrafluoroethylene (PTFE) layer is designed to rapidly export exudate and accelerate diabetic wound healing. In the design, the ice-templating process endows the hydrophilic hydrogel layer with superior liquid transport ability and mechanical strength due to the formation of aligned channel structure. The hydrophobic layer with controlled thickness functions as an effective barrier to prevent exudate from wetting the skin surface. Experiments in diabetic rat model show that JHA can significantly promote re-epithelialization and collagen deposition, shorten the inflammation phase, and accelerate wound healing. This unique JHA dressing may have great potential for real-life usage in clinical patients.

Mechanical property analysis and design parameter optimization of a novel nitinol nasal stent based on numerical simulation.

Background: A novel braided nasal stent is an effective alternative to nasal packing after septoplasty that can be used to manage the mucosal flap after septoplasty and expand the nasal cavity. This study aimed to investigate the influence of design parameters on the mechanical properties of the nasal stent for optimal performance. Methods: A braided nasal stent modeling method was proposed and 27 stent models with a range of different geometric parameters were built. The compression behavior and bending behavior of these stent models were numerically analyzed using a finite element method (FEM). The orthogonal test was used as an optimization method, and the optimized design variables of the stent with improved performance were obtained based on range analysis and weight grade method. Results: The reaction force and bending stiffness of the braided stent increased with the wire diameter, braiding density, and external stent diameter, while wire diameter resulted as the most important determining parameter. The external stent diameter had the greatest influence on the elongation deformation. The influence of design parameters on von-Mises stress distribution of bent stent models was visualized. The stent model with geometrical parameters of 25 mm external diameter, 30° braiding angle, and 0.13 mm wire diameter (A3B3C3) had a greater reaction force but a considerably smaller bending stiffness, which was the optimal combination of parameters. Conclusion: Firstly, among the three design parameters of braided stent models, wire diameter resulted as the most important parameter determining the reaction force and bending stiffness. Secondly, the external stent diameter significantly influenced the elongation deformation during the compression simulation. Finally, 25 mm external diameter, 30° braiding angle, and 0.13 mm wire diameter (A3B3C3) was the optimal combination of stent parameters according to the orthogonal test results.

Study on feasibility of the partial meniscal allograft transplantation.

Since the meniscus is an important stabilizing structure of the knee joint and has a significant role in load-bearing and shock absorption, so the complete structural and functional reconstructions of the teared menisci should be done not only after partial meniscectomy but also post total meniscectomy. So far, animal experiments and good clinical practice have showed that TMAT after total meniscectomy has partially solved the problem of structural and functional reconstructions after total meniscectomy. However, partial meniscectomy will also lead to accelerated knee degeneration, and its proportion is much higher than that of patients with total meniscectomy. Herein, the feasibility of PMAT after partial meniscectomy was investigated for the first time by using the 40% posterior horn meniscectomy model of the medial meniscus in Beagle dogs, and also for the first time, TMAT group and the total meniscectomy group were used as control groups. Compared with the TMAT, the transcriptomics evaluation, scanning electron microscope observation, histological regeneration and structure, biomechanical property, inflammation environment, and the knee function post PMAT were more similar to that of normal meniscus was first reported. This study provides a PMAT scheme with clinical translational value for the complete structural and functional reconstruction of the patients with partial meniscectomy and fills the gap in the field of teared meniscus therapy on the basis of quite well clinical applications of the meniscus repair and the TMAT.

Principles for establishment of the stem cell bank and its applications on management of sports injuries.

BACKGROUND: The stem cells of the stem cell banks have prominent problems for insufficient sources, easy contamination, unstable biological characteristics after serial subcultivations, and high cost. METHODS: After collecting the construction processes of the existing stem cell banks and suggestions from authoritative experts in the past 10 years, 230 reference principles were obtained, and finally, the principles of "5C" for the establishment of modern standardized stem cell banks were summarized, and their related applications on the management of sports injuries were reviewed as well. RESULTS: The basic principles of "5C" for the establishment of modern standardized stem cell banks include (1) principle of informed consent, (2) confidentiality principle, (3) conformity principle, (4) contamination-free principle, and (5) commonweal principle. The applications of stem cells on repairs, reconstructions, and regenerations of sports injuries were also reviewed, especially in tissue-engineered cartilage, tissue-engineered meniscus, and tissue-engineered ligament. CONCLUSIONS: The proposal of the basic principles of "5C" is conducive to relevant stem cell researchers and clinical medical experts to build modern stem cell banks in a more standardized and efficient manner while avoiding some major mistakes or problems that may occur in the future. On this basis, stem cells from stem cell banks would be increasingly used in the management of sports injuries. More importantly, these days, getting stem cell samples are difficult in a short time, and such banks with proper legal consent may help the scientific community.

MicroRNA-210-3p Promotes Chondrogenic Differentiation and Inhibits Adipogenic Differentiation Correlated with HIF-3α Signalling in Bone Marrow Mesenchymal Stem Cells.

Cartilage injury of the knee joint is very common. Due to the limited self-healing ability of articular cartilage, osteoarthritis is very likely to occur if left untreated. Bone marrow mesenchymal stem cells (BMMSCs) are widely used in the study of cartilage injury due to their low immunity and good amplification ability, but they still have disadvantages, such as heterogeneous undifferentiated cells. MicroRNAs can regulate the chondrogenic differentiation ability of MSCs by inhibiting or promoting mRNA translation and degradation. In this research, we primarily investigated the effect of microRNA-210-3p (miR-210-3p) on chondrogenic and adipogenic differentiation of BMMSCs in vitro. Our results demonstrate that miR-210-3p promoted chondrogenic differentiation and inhibited adipogenic differentiation of rat BMMSCs, which was related to the HIF-3α signalling pathway. Additionally, miR-210-3p promotes mRNA and protein levels of the chondrogenic expression genes COLII and SOX9 and inhibits mRNA and protein levels of the adipogenic expression genes PPARγ and LPL. Thus, miR-210-3p combined with BMMSCs is a candidate for future clinical applications in cartilage regeneration and could represent a promising new therapeutic target for OA.

A Systematic Review of Tissue Engineering Scaffold in Tendon Bone Healing in vivo.

Background: Tendon-bone healing is an important factor in determining the success of ligament reconstruction. With the development of biomaterials science, the tissue engineering scaffold plays an extremely important role in tendon-bone healing and bone tissue engineering. Materials and Methods: Electronic databases (PubMed, Embase, and the Web of Science) were systematically searched for relevant and qualitative studies published from 1 January 1990 to 31 December 2019. Only original articles that met eligibility criteria and evaluated the use of issue engineering scaffold especially biomaterials in tendon bone healing in vivo were selected for analysis. Results: The search strategy identified 506 articles, and 27 studies were included for full review including two human trials and 25 animal studies. Fifteen studies only used biomaterials like PLGA, collage, PCL, PLA, and PET as scaffolds to repair the tendon-bone defect, on this basis, the rest of the 11 studies using biological interventions like cells or cell factors to enhance the healing. The adverse events hardly ever occurred, and the tendon bone healing with tissue engineering scaffold was effective and superior, which could be enhanced by biological interventions. Conclusion: Although a number of tissue engineering scaffolds have been developed and applied in tendon bone healing, the researches are mainly focused on animal models which are with limitations in clinical application. Since the efficacy and safety of tissue engineering scaffold has been proved, and can be enhanced by biological interventions, substantial clinical trials remain to be done, continued progress in overcoming current tissue engineering challenges should allow for successful clinical practice.

Tibial Tubercle Osteotomy May Not Provide Additional Benefit in Treating Patellar Dislocation With Increased Tibial Tuberosity-Trochlear Groove Distance: A Systematic Review.

PURPOSE: To examine the indications and outcomes of medial patellofemoral ligament reconstruction (MPFLR) with or without tibial tubercle osteotomy (TTO) in treating recurrent or habitual patellar dislocation with an increased tibial tuberosity-trochlear groove (TT-TG) distance. METHODS: We performed a literature search of the established medical databases Cochrane Central, PubMed-MEDLINE, EMBASE, and Web of Science. The inclusion criteria were as follows: skeletally mature patients with recurrent or habitual patellar dislocation and an increased TT-TG distance, treatment with MPFLR combined with a TTO procedure or isolated MPFLR, and reporting of clinical outcomes and complications. Each study was assessed for quality and the level of evidence. The general characteristics, indications, surgical techniques, TT-TG distance, clinical results, imaging evaluation findings, and complications of each study were recorded. RESULTS: Nine studies consisting of 288 knees met the inclusion criteria. The average Coleman score was 71.56 (range, 55-83). The threshold for an increased TT-TG distance ranged from 16 to 20 mm in the included studies. Similar good postoperative outcomes were reported in patients with an increased TT-TG distance treated with MPFLR with versus without a TTO procedure. The mean postoperative Lysholm score ranged from 75.0 to 94.7 (I2 = 87.6%) in the isolated MPFLR group and from 85.0 to 87.6 (I2 = 16.3%) in the TTO-with-MPFLR group. Similar postoperative congruence angles were reported in both groups. The postoperative redislocation rate ranged from 0% to 4.2% in the TTO-with-MPFLR group, and no redislocation was found in the isolated MPFLR group. The postoperative apprehension sign was only reported in isolated MPFLR patients. CONCLUSIONS: The outcomes of MPFLR with or without TTO to treat recurrent or habitual patellar dislocation with an increased TT-TG distance appeared similar. However, this study was limited by the considerable heterogeneity, variety of techniques, variety of TT-TG distances, and variability in patella alta and trochlear dysplasia among the included studies. LEVEL OF EVIDENCE: Level IV, systematic review of Level II to IV studies.

Discovery of Selenocysteine as a Potential Nanomedicine Promotes Cartilage Regeneration With Enhanced Immune Response by Text Mining and Biomedical Databases.

BACKGROUND: Unlike bone tissue, little progress has been made regarding cartilage regeneration, and many challenges remain. Furthermore, the key roles of cartilage lesion caused by traumas, focal lesion, or articular overstress remain unclear. Traumatic injuries to the meniscus as well as its degeneration are important risk factors for long-term joint dysfunction, degenerative joint lesions, and knee osteoarthritis (OA) a chronic joint disease characterized by degeneration of articular cartilage and hyperosteogeny. Nearly 50% of the individuals with meniscus injuries develop OA over time. Due to the limited inherent self-repair capacity of cartilage lesion, the Biomaterial drug-nanomedicine is considered to be a promising alternative. Therefore, it is important to elucidate the gene potential regeneration mechanisms and discover novel precise medication, which are identified through this study to investigate their function and role in pathogenesis. METHODS: We downloaded the mRNA microarray statistics GSE117999, involving paired cartilage lesion tissue samples from 12 OA patients and 12 patients from a control group. First, we analyzed these statistics to recognize the differentially expressed genes (DEGs). We then exposed the gene ontology (GO) annotation and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses for these DEGs. Protein-protein interaction (PPI) networks were then constructed, from which we attained eight significant genes after a functional interaction analysis. Finally, we identified a potential nanomedicine attained from this assay set, using a wide range of inhibitor information archived in the Search Tool for the Retrieval of Interacting Genes (STRING) database. RESULTS: Sixty-six DEGs were identified with our standards for meaning (adjusted P-value < 0.01, |log2 - FC| ≥1.2). Furthermore, we identified eight hub genes and one potential nanomedicine - Selenocysteine based on these integrative data. CONCLUSION: We identified eight hub genes that could work as prospective biomarkers for the diagnostic and biomaterial drug treatment of cartilage lesion, involving the novel genes CAMP, DEFA3, TOLLIP, HLA-DQA2, SLC38A6, SLC3A1, FAM20A, and ANO8. Meanwhile, these genes were mainly associated with immune response, immune mediator induction, and cell chemotaxis. Significant support is provided for obtaining a series of novel gene targets, and we identify potential mechanisms for cartilage regeneration and final nanomedicine immunotherapy in regenerative medicine.

The Higher Inherent Therapeutic Potential of Biomaterial-Based hDPSCs and hEnSCs for Pancreas Diseases.

Human endometrial stem cells (hEnSCs), dental pulp stem cells (hDPSCs) and adipose tissue-derived stem cells (hADSCs) are considered to be the promising candidates for the treatment of pancreas diseases. The prognosis is better with in situ injection of mesenchymal stem cells (MSCs) to the damaged pancreas compared with intravenous injection. However, the clinical application of these cells are limited, due to poor engraftment of transplanted cells after delivery. On the other hand, understanding the role of the biomaterials in cell therapy is essential to promote the therapeutic effects of MSCs. Matrigel, a basement membrane matrix biomaterial, is rich in laminin and collagen IV. The aim of this study is to investigate the difference of biological characteristics of hEnSCs, hDPSCs and hADSCs in vitro and their survival situation with Matrigel post intrapancreatic transplantation in vivo. Our findings showed, firstly, there was no significant difference in morphology and immunophenotype of these MSCs. Secondly, the biological properties, including cell proliferation, the ability of adipogenic and osteogenic differentiation and the mRNA expression levels of pancreas development-related genes, have been showed distinct difference among these MSCs. Thirdly, Matrigel can improve the survival of MSCs in vivo, especially for Matrigel-based hDPSCs and Matrigel-based hEnSCs in pancreas parenchyma of SD rats. These results suggest that hDPSCs and hEnSCs are with the greater inherent therapeutic potential for pancreas diseases compared with hADSCs.

Advances of Stem Cell-Laden Hydrogels With Biomimetic Microenvironment for Osteochondral Repair.

Osteochondral damage from trauma or osteoarthritis is a general joint disease that can lead to an increased social and economic burden in the modern society. The inefficiency of osteochondral defects is mainly due to the absence of suitable tissue-engineered substrates promoting tissue regeneration and replacing damaged areas. The hydrogels are becoming a promising kind of biomaterials for tissue regeneration. The biomimetic hydrogel microenvironment can be tightly controlled by modulating a number of biophysical and biochemical properties, including matrix mechanics, degradation, microstructure, cell adhesion, and intercellular interactions. In particular, advances in stem cell-laden hydrogels have offered new ideas for the cell therapy and osteochondral repair. Herein, the aim of this review is to underpin the importance of stem cell-laden hydrogels on promoting the development of osteochondral regeneration, especially in the field of manipulation of biomimetic microenvironment and utilization growth factors with various delivery methods.

The Use of Peripheral Blood-Derived Stem Cells for Cartilage Repair and Regeneration In Vivo: A Review.

BACKGROUND: Peripheral blood (PB) is a potential source of chondrogenic progenitor cells that can be used for cartilage repair and regeneration. However, the cell types, isolation and implantation methods, seeding dosage, ultimate therapeutic effect, and in vivo safety remain unclear. METHODS: PubMed, Embase, and the Web of Science databases were systematically searched for relevant reports published from January 1990 to December 2019. Original articles that used PB as a source of stem cells to repair cartilage in vivo were selected for analysis. RESULTS: A total of 18 studies were included. Eight human studies used autologous nonculture-expanded PB-derived stem cells (PBSCs) as seed cells with the blood cell separation isolation method, and 10 animal studies used autologous, allogenic or xenogeneic culture-expanded PB-derived mesenchymal stem cells (PB-MSCs), or nonculture-expanded PBSCs as seed cells. Four human and three animal studies surgically implanted cells, while the remaining studies implanted cells by single or repeated intra-articular injections. 121 of 130 patients (in 8 human clinical studies), and 230 of 278 animals (in 6 veterinary clinical studies) using PBSCs for cartilage repair achieved significant clinical improvement. All reviewed articles indicated that using PB as a source of seed cells enhances cartilage repair in vivo without serious adverse events. CONCLUSION: Autologous nonculture-expanded PBSCs are currently the most commonly used cells among all stem cell types derived from PB. Allogeneic, autologous, and xenogeneic PB-MSCs are more widely used in animal studies and are potential seed cell types for future applications. Improving the mobilization and purification technology, and shortening the culture cycle of culture-expanded PB-MSCs will obviously promote the researchers' interest. The use of PBSCs for cartilage repair and regeneration in vivo are safe. PBSCs considerably warrant further investigations due to their superiority and safety in clinical settings and positive effects despite limited evidence in humans.