A Multifunctional Nanocomposite Hydrogel for Endoscopic Tracking and Manipulation

Herein, the fabrication of multi‐responsive and hierarchically organized nanomaterial using core‐shell SrF2 upconverting nanoparticles, doped with Yb3+, Tm3+, Nd3+ incorporated into gelatin methacryloyl matrix, is reported. Upon 800 nm excitation, deep monitoring of 3D‐printed constructs is demonstrated. Addition of magnetic self‐assembly of iron oxide nanoparticles within the hydrogel provides anisotropic structuration from the nano‐ to the macro‐scale and magnetic responsiveness permitting remote manipulation. The present study provides a new strategy for the fabrication of a novel highly organized multi‐responsive material using additive manufacturing, which can have important implications in biomedicine

Tissue-specific melt electrowritten polymeric scaffolds for coordinated regeneration of soft and hard periodontal tissues

Periodontitis is a chronic inflammatory condition that often causes serious damage to tooth-supporting tissues. The limited successful outcomes of clinically available approaches underscore the need for therapeutics that cannot only provide structural guidance to cells but can also modulate the local immune response. Here, three-dimensional melt electrowritten ( i.e., poly(ε-caprolactone)) scaffolds with tissue-specific attributes were engineered to guide differentiation of human-derived periodontal ligament stem cells (hPDLSCs) and mediate macrophage polarization. The investigated tissue-specific scaffold attributes comprised fiber morphology (aligned vs. random) and highly-ordered architectures with distinct strand spacings (small 250 μm and large 500 μm). Macrophages exhibited an elongated morphology in aligned and highly-ordered scaffolds, while maintaining their round-shape on randomly-oriented fibrous scaffolds. Expressions of periostin and IL-10 were more pronounced on the aligned and highly-ordered scaffolds. While hPDLSCs on the scaffolds with 500 μm strand spacing show higher expression of osteogenic marker (Runx2) over 21 days, cells on randomly-oriented fibrous scaffolds showed upregulation of M1 markers. In an orthotopic mandibular fenestration defect model, findings revealed that the tissue-specific scaffolds ( i.e., aligned fibers for periodontal ligament and highly-ordered 500 μm strand spacing fluorinated calcium phosphate [F/CaP]-coated fibers for bone) could enhance the mimicking of regeneration of natural periodontal tissues

Human adult, pediatric and microtia auricular cartilage harbor fibronectin-adhering progenitor cells with regenerative ear reconstruction potential

Remaining challenges in auricular cartilage tissue engineering include acquiring sufficient amounts of regeneration-competent cells and subsequent production of high-quality neocartilage. Progenitor cells are a resident subpopulation of native cartilage, displaying a high proliferative and cartilage-forming capacity, yet their potential for regenerative medicine is vastly understudied. In this study, human auricular cartilage progenitor cells were newly identified in healthy cartilage and, importantly, in microtia-impaired chondral remnants. Their cartilage repair potential was assessed via in vitro 3D culture upon encapsulation in a gelatin-based hydrogel, and subsequent biochemical, mechanical, and histological analyses. Auricular cartilage progenitor cells demonstrate a potent ability to proliferate without losing their multipotent differentiation ability and to produce cartilage-like matrix in 3D culture. As these cells can be easily obtained through a non-deforming biopsy of the healthy ear or from the otherwise redundant microtia remnant, they can provide an important solution for long-existing challenges in auricular cartilage tissue engineering

Timing of Vertical Head, Withers and Pelvis Movements Relative to the Footfalls in Different Equine Gaits and Breeds

Knowledge of vertical motion patterns of the axial body segments is a prerequisite for the development of algorithms used in automated detection of lameness. To date, the focus has been on the trot. This study investigates the temporal synchronization between vertical motion of the axial body segments with limb kinematic events in walk and trot across three popular types of sport horses (19 Warmbloods, 23 Iberians, 26 Icelandics) that are known to have different stride kinematics, and it presents novel data describing vertical motion of the axial body segments in tölting and pacing Icelandic horses. Inertial measurement unit sensors recorded limb kinematics, vertical motion of the axial body at all symmetrical gaits that the horse could perform (walk, trot, tölt, pace). Limb kinematics, vertical range of motion and lowest/highest positions of the head, withers and pelvis were calculated. For all gaits except walk and pace, lowest/highest positions of the pelvis and withers were found to be closely related temporally to midstance and start of suspension of the hind/fore quarter, respectively. There were differences in pelvic/withers range of motion between all breeds where the Icelandic horses showed the smallest motion, which may explain why lameness evaluation in this breed is challenging

Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation

Background: Allogenic mesenchymal stem cell (MSC) secretome is a novel intra-articular therapeutic that has shown promise in in vitro and small animal models and warrants further investigation. Objectives: To investigate if intra-articular allogenic MSC-secretome has anti-inflammatory effects using an equine model of joint inflammation. Study Design: Randomized positively and negatively controlled experimental study. Method: In phase 1, joint inflammation was induced bilaterally in radiocarpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After 2 h, the secretome of INFy and TNFα stimulated allogeneic equine MSCs was injected in one randomly assigned joint, while the contralateral joint was injected with medium (negative control). Clinical parameters (composite welfare scores, joint effusion, joint circumference) were recorded, and synovial fluid samples were analyzed for biomarkers (total protein, WBCC; eicosanoid mediators, CCL2; TNFα; MMP; GAGs; C2C; CPII) at fixed post-injection hours (PIH 0, 8, 24, 72, and 168 h). The effects of time and treatment on clinical and synovial fluid parameters and the presence of time-treatment interactions were evaluated. For phase 2, allogeneic MSC-secretome vs. allogeneic equine MSCs (positive control) was tested using a similar methodology. Results: In phase 1, the joint circumference was significantly (p < 0.05) lower in the MSC-secretome treated group compared to the medium control group at PIH 24, and significantly higher peak synovial GAG values were noted at PIH 24 (p < 0.001). In phase 2, no significant differences were noted between the treatment effects of MSC-secretome and MSCs. Main Limitations: This study is a controlled experimental study and therefore cannot fully reflect natural joint disease. In phase 2, two therapeutics are directly compared and there is no negative control. Conclusions: In this model of joint inflammation, intra-articular MSC-secretome injection had some clinical anti-inflammatory effects. An effect on cartilage metabolism, evident as a rise in GAG levels was also noted, although it is unclear whether this could be considered a beneficial or detrimental effect. When directly comparing MSC-secretome to MSCs in this model results were comparable, indicating that MSC-secretome could be a viable off-the-shelf alternative to MSC treatment

Small molecules to regulate the GH/IGF1 axis by inhibiting the growth hormone receptor synthesis

Growth hormone (GH) and insulin-like growth factor-1 (IGF1) play an important role in mammalian development, cell proliferation and lifespan. Especially in cases of tumor growth there is an urgent need to control the GH/IGF1 axis. In this study we screened a 38,480-compound library, and in two consecutive rounds of analogues selection, we identified active lead compounds based on the following criteria: inhibition the GH receptor (GHR) activity and its downstream effectors Jak2 and STAT5, and inhibition of growth of breast and colon cancer cells. The most active small molecule (BM001) inhibited both the GH/IGF1 axis and cell proliferation with an IC50 of 10-30 nM of human cancer cells. BM001 depleted GHR in human lymphoblasts. In preclinical xenografted experiments, BM001 showed a strong decrease in tumor volume in mice transplanted with MDA-MB-231 breast cancer cells. Mechanistically, the drug acts on the synthesis of the GHR. Our findings open the possibility to inhibit the GH/IGF1 axis with a small molecule

Harnessing light in biofabrication

The integration of light-driven technologies into biofabrication has revolutionized the field of tissue engineering and regenerative medicine, with numerous breakthroughs in the last few years. Light-based bioprinting approaches (lithography, multiphoton and volumetric bioprinting) have shown the potential to fabricate large scale tissue engineering constructs of high resolution, with great flexibility and control over the cellular organization. Given the unprecedented degree of freedom in fabricating convoluted structures, key challenges in regenerative medicine, such as introducing complex channels and pre-vascular networks in 3D constructs have also been addressed. Light has also been proven as a powerful tool, leading to novel photo-chemistry in designing bioinks, but also able to impart spatial-temporal control over cellular functions through photo-responsive chemistry. For instance, smart constructs able to undergo remotely controlled shape changes, stiffening, softening and degradation can be produced. The non-invasive nature of light stimulation also enables to trigger such responses post-fabrication, during the maturation phase of a construct. Such unique ability can be used to mimic the dynamic processes occurring in tissue regeneration, as well as in disease progression and degenerative processes in vivo. Bringing together these novel multidisciplinary expertise, the present Special Issue aims to discuss the most recent trends, strategies and novel light-based technologies in the field of biofabrication. These include: 1) using light-based bioprinting to develop in vitro models for drug screening, developmental biology models, disease models, and also functional tissues for implantation; 2) novel light-based biofabrication technologies; 3) development of new photo-responsive bioinks or biomaterial inks

Detecting fatigue of sport horses with biomechanical gait features using inertial sensors

Detection of fatigue helps prevent injuries and optimize the performance of horses. Previous studies tried to determine fatigue using physiological parameters. However, measuring the physiological parameters, e.g., plasma lactate, is invasive and can be affected by different factors. In addition, the measurement cannot be done automatically and requires a veterinarian for sample collection. This study investigated the possibility of detecting fatigue non-invasively using a minimum number of body-mounted inertial sensors. Using the inertial sensors, sixty sport horses were measured during walk and trot before and after high and low-intensity exercises. Then, biomechanical features were extracted from the output signals. A number of features were assigned as important fatigue indicators using neighborhood component analysis. Based on the fatigue indicators, machine learning models were developed for classifying strides to non-fatigue and fatigue. As an outcome, this study confirmed that biomechanical features can indicate fatigue in horses, such as stance duration, swing duration, and limb range of motion. The fatigue classification model resulted in high accuracy during both walk and trot. In conclusion, fatigue can be detected during exercise by using the output of body-mounted inertial sensors

Collagen Microfibers Induce Blood Capillary Orientation and Open Vascular Lumen

Achieving vascularization of engineered tissues or structures is a major challenge in the field of tissue engineering. Hitherto, studies on vascularization have demonstrated limited control of vascular network geometry, such as vasculature direction and network density. An open vascular lumen is crucial to ensure that cells survive and that metabolic activity is fully functional in large‐sized tissues. Herein, a method based on high water‐dispersible collagen microfibers (CMF) to fabricate capillary orientation‐controllable 3D tissue with an open vascular lumen using a dispensing machine is reported. A twenty micrometers‐long CMF (CMF‐20) with high dispersion property are shown to be more effective for dispensing a homogenous tissue and inducing formation of an interconnected capillary network than two hundred micrometers‐long CMF (CMF‐200). One of the advantages is the prevention of shrinkage on the z‐axis of hydrogel‐based tissue which acts as a microscaffold. The gaps between the fibers can support endothelial cell migration and maturation, thus forming a larger vascular lumen compared to CMF‐free controls. Besides, shear forces produced by the dispensing process cause the collagen microfibers to align, and these microfibers guide cell alignment by integrin‐induced adhesion. The findings based on CMF to allow blood capillary alignment and vascular lumen stabilization will be an important technology in tissue engineering