New Insight into Natural Extracellular Matrix: Genipin Cross-Linked Adipose-Derived Stem Cell Extracellular Matrix Gel for Tissue Engineering.

The cell-derived extracellular matrix (ECM) is associated with a lower risk of pathogen transfer, and it possesses an ideal niche with growth factors and complex fibrillar proteins for cell attachment and growth. However, the cell-derived ECM is found to have poor biomechanical properties, and processing of cell-derived ECM into gels is scarcely studied. The gel provides platforms for three-dimensional cell culture, as well as injectable biomaterials, which could be delivered via a minimally invasive procedure. Thus, in this study, an adipose-derived stem cell (ADSC)-derived ECM gel was developed and cross-linked by genipin to address the aforementioned issue. The genipin cross-linked ADSC ECM gel was fabricated via several steps, including rabbit ADSC culture, cell sheets, decellularization, freeze-thawing, enzymatic digestion, neutralization of pH, and cross-linking. The physicochemical characteristics and cytocompatibility of the gel were evaluated. The results demonstrated that the genipin cross-linking could significantly enhance the mechanical properties of the ADSC ECM gel. Furthermore, the ADSC ECM was found to contain collagen, fibronectin, biglycan, and transforming growth factor (TGF)-ß1, which could substantially maintain ADSC, skin, and ligament fibroblast cell proliferation. This cell-derived natural material could be suitable for future regenerative medicine and tissue engineering application.

Bioactive Glass Fiber-Reinforced Plastic Composites Prompt a Crystallographic Lophelia Atoll-Like Skeletal Microarchitecture Actuating Periosteal Cambium.

The touchstone for bone replacing or anchoring trauma implants, besides resorption, includes functional ankylosis at a fixation point and replacement by viable functional neo-bone tissues. These parameters redefined the concept of "resorbability" as "bioresorbability." Interference screws are the most commonly used resorbable anchoring implants for anterior cruciate ligament (ACL) reconstruction (surgery). Over the years, the bioresorbable screw fixation armamentarium has amplified countless choices, but instability and postimplantation complications have raised concerns about its reliability and efficacy. Owing to this interest, in this work, bioactive glass fiber-reinforced plastic (BGFP) composites with (BGFPnb5) and without (BGFP5) niobicoxide composing multiplexed network modifiers are reported as bioresorbable bone-anchoring substitutes. These synergistically designed composites have a fabricated structure of continuous, unidirectional BG fibers reinforced in an epoxy resin matrix using "melt-drawing and microfabrication" technology. The BGFP microarchitecture is comprised of multiplexed oxide components that influence bioactive response in a distinctive lophelia atoll-like apatite formation. Furthermore, it assists in the proliferation, adherence, and migration of bone marrow-derived mesenchymal stem cells. It also exhibits superior physicochemical characteristics such as surface roughness, hydrophilic exposure, distinctive flexural strength, and bioresorption. Thus, it induces restorative bone osseointegration and osteoconduction and actuates periosteum function. In addition, the BGFP influences the reduction of DH5-α Escherichia coli in suspension culture, demonstrating potential antibacterial efficacy. In conclusion, the BGFP composite therapeutic efficacy demonstrates distinctive material characteristics aiding in bone regeneration and restoration that could serve as a pioneer in orthopedic regenerative medicine.

Effectiveness of treating segmental bone defects with a synergistic co-delivery approach with platelet-rich fibrin and tricalcium phosphate.

Several studies have applied tricalcium phosphate (TCP) or autografts in bone tissue engineering to enhance the clinical regeneration of bone. Unfortunately, there are several drawbacks related to the use of autografts, including a risk of infection, blood loss, limited quantities, and donor-site morbidities. Platelet-rich fibrin (PRF) is a natural extracellular matrix (ECM) biomaterial that possesses bioactive factors, which can generally be used in regenerative medicine. The goal of the present investigation was to develop osteoconductive TCP incorporated with bioactive PRF for bio-synergistic bone regeneration and examine the potential biological mechanisms and applications. Our in vitro results showed that PRF plus TCP had excellent biosafety and was favorable for initiating osteoblast cell attachment, slow release of bioactive factors, cell proliferation, cell migration, and ECM formation that potentially impacted bone repair. In a rabbit femoral segmental bone defect model, regeneration of bone was considerably augmented in defects locally implanted by PRF plus TCP according to radiographic and histologic examinations. Notably, the outcomes of this investigation suggest that the combination of PRF and TCP possesses novel synergistic and bio-inspired functions that facilitate bone regeneration.

Digital interventions self-management education for type 1 and 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: To describe and assess digital health-led diabetes self-management education and support (DSMES) effectiveness in improving glycosylated hemoglobin, diabetes knowledge, and health-related quality of life (HrQoL) of Type 1 and 2 Diabetes in the past 10 years. DESIGN: Systematic Review and Meta-Analysis. The protocol was registered on PROSPERO registration number CRD42019139884. DATA SOURCES: PubMed, EMBASE, Cochrane library, Web of Science, and Scopus between January 2010 and August 2019. Study Selection and Appraisal: Randomized control trials of digital health-led DSMES for Type 1 (T1DM) or 2 (T2DM) diabetes compared to usual care were included. Outcomes were change in HbA1c, diabetes knowledge, and HrQoL. Cochrane Risk of Bias 2.0 tool was used to assess bias and GRADEpro for overall quality. The analysis involved narrative synthesis, subgroup and pooled meta-analyses. RESULTS: From 4286 articles, 39 studies (6861 participants) were included. Mean age was 51.62 years, range (13-70). Meta-analysis revealed intervention effects on HbA1c for T2DM with difference in means (MD) from baseline -0.480% (-0.661, -0.299), I275% (6 months), -0.457% (-0.761, -0.151), I2 81% (12 months), and for T1DM -0.41% (-1.022, 0.208) I2 83% (6 months), -0.03% (-0.210, 0.142) I2 0% (12 months). Few reported HrQoL with Hedges' g 0.183 (-0.039, 0.405), I2 0% (6 months), 0.153 (-0.060, 0.366), I2 0% (12 months) and diabetes knowledge with Hedges' g 1.003 (0.068, 1.938), I2 87% (3 months). CONCLUSION: Digital health-led DSMES are effective in improving HbA1c and diabetes knowledge, notably for T2DM. Research shows non-significant changes in HrQoL. Intervention effect on HbA1c was more impressive if delivered through mobile apps or patient portals. Further research is needed on the impact of DSMES on these outcomes, especially for newly diagnosed diabetes patients.

Label-Free, Smartphone-Based, and Sensitive Nano-Structural Liquid Crystal Aligned by Ceramic Silicon Compound-Constructed DMOAP-Based Biosensor for the Detection of Urine Albumin.

INTRODUCTION: The sensitive interfacial interaction of liquid crystals (LC) holds potential for precision biosensors. In the past, the developments of LC biosensors were limited by the complicated manufacturing process, which hinders commercialization and wider applications of such devices. In this report, we demonstrate the first nano-structural polymeric stabilized-cholesteric LC (PSCLC) thin films to be a new label-free biosensing technology. METHODS: The transmission spectra of PSCLC devices were measured by the fiber-optic spectrometer with high-resolution. In addition, a smartphone was set on the stage, and the camera of smartphone was placed and aligned with a set of lenses embedded in the designed stage. To decrease the chromatic and spherical aberrations, an achromatic lens set composition, consisting of both dual-convex lens and concave-plane lens, was applied for measuring and imaging the PSCLC texture. The average and the estimated standard deviation (SD) were used to present quantitative experimental results. The test BSA was immobilized and fulfilled by the ceramic silicon-constructed DMOAP-coated glass in aqueous BSA solutions at 1 mg/mL, 1 µg/mL, and 1 ng/mL. RESULTS: The fabrication process of PSCLC is much simplified compared to previous LC biosensors. The color of PSCLC biosensor altered with the BSA concentration, making detection result easy to read. The detection limit of 1 ng/mL is achieved for label-free PSCLC biosensor. The PSCLC biosensor was able to successfully detect due to the albumin concentration's alteration, with a linear range of 1 ng/mL-2 mg/mL. Thus, the label-free-proposed design-integrated nanoscale PSCLCs smartphone-based biosensor could successfully detect BSA in a preclinical urine sample. CONCLUSION: Finally, we propose a design to integrate the PSCLC biosensor with a smartphone. The PSCLC owns potential for high performance, low cost for detecting various disease biomarkers in home use. Owing to its great potential for high performance and low cost, the PSCLC biosensors can be used as a label-free point-of-care for detecting various disease biomarkers for patients in care homes.

Strontium ranelate-laden near-infrared photothermal-inspired methylcellulose hydrogel for arthritis treatment.

Rheumatoid arthritis (RA) is of foremost concern among long-term autoimmune disorders, as it leads to inflammation, exudates, chondral degeneration, and painful joints. Because RA severity often fluctuates over time, a local drug delivery method that titrates release of therapeutics to arthritis bioactivity should represent a promising paradigm of RA therapy. Given the local nature of RA chronic illnesses, polysaccharide-drug delivering systems have the promise to augment therapeutic outcomes by offering controlled release of bioactive materials, diminishing the required frequency of administration, and preserving therapeutic levels in affected pathological regions. Herein, an intra-articular photothermal-laden injectable methylcellulose (MC) polymeric hydrogel carrier incorporating strontium ranelate (SrR) and sodium chloride was investigated to resolve these issues. Physicochemical and cellular characteristics of the MC carrier system were thoroughly evaluated. The slow release of SrR, enhancement of the material mechanical strength, and the potential of the non-invasive near-infrared photothermal gel to improve blood circulation and suppress inflammation in a mini-surgical model of RA were examined. Biocompatibility and suppression of intracellular ROS-induced inflammation were observed. This multifunctional photothermal MC hydrogel carrier is anticipated to be an alternative approach for future orthopedic disease treatment.

Facilitated and Controlled Strontium Ranelate Delivery Using GCS-HA Nanocarriers Embedded into PEGDA Coupled with Decortication Driven Spinal Regeneration.

BACKGROUND AND PURPOSE: Strontium ranelate (SrR) is an oral pharmaceutical agent for osteoporosis. In recent years, numerous unwanted side effects of oral SrR have been revealed. Therefore, its clinical administration and applications are limited. Hereby, this study aims to develop, formulate, and characterize an effective SrR carrier system for spinal bone regeneration. METHODS: Herein, glycol chitosan with hyaluronic acid (HA)-based nanoformulation was used to encapsulate SrR nanoparticles (SrRNPs) through electrostatic interaction. Afterward, the poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels were used to encapsulate pre-synthesized SrRNPs (SrRNPs-H). The scanning electron microscope (SEM), TEM, rheometer, Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used to characterize prepared formulations. The rabbit osteoblast and a rat spinal decortication models were used to evaluate and assess the developed formulation biocompatibility and therapeutic efficacy. RESULTS: In vitro and in vivo studies for cytotoxicity and bone regeneration were conducted. The cell viability test showed that SrRNPs exerted no cytotoxic effects in osteoblast in vitro. Furthermore, in vivo analysis for new bone regeneration mechanism was carried out on rat decortication models. Radiographical and histological analysis suggested a higher level of bone regeneration in the SrRNPs-H-implanted groups than in the other experimental groups. CONCLUSION: Local administration of the newly developed formulated SrR could be a promising alternative therapy to enhance bone regeneration in bone-defect sites in future clinical applications.

Photothermal-Irradiated Polyethyleneimine-Polypyrrole Nanopigment Film-Coated Polyethylene Fabrics for Infrared-Inspired with Pathogenic Evaluation.

Influenza, pneumonia, and pathogenic infection of the respiratory system are boosted in cold environments. Low temperatures also result in vasoconstriction, restraint of blood flow, and decreased oxygen to the heart, and the risk of a heart attack would increase accordingly. The present face mask fabric fails to preserve its air-filtering function as its electrostatic function vanishes once exposed to water. Therefore, its filtering efficacy would be decreased meaningfully, making it nearly impracticable to reuse the disposable face masks. The urgent requirement for photothermal fabrics is also rising. Nanobased polyethyleneimine-polypyrrole nanopigments (NPP NPs) have been developed and have strong near-infrared spectrum absorption and exceptional photothermal convertible performance. Herein, the mask fabric used PE-fiber-constructed membrane (PEFM) was coated by the binding affinity of the cationic polyethyleneimine component of NPP NPs forming NPP NPs-PEFM. To the best of our knowledge, no study has investigated NPP NP-coated mask fabric to perform infrared red (solar or body) photothermal conversion efficacy to provide biocompatible warming, remotely photothermally captured antipathogen, and antivasoconstriction in vivo. This pioneering study showed that the developed NPP NPs-PEFM could be washable, reusable, breathable, biocompatible, and photothermal conversable for active eradication of pathogenic bacteria. Further, it possesses warming preservation and antivasoconstriction.

Microplasma Cross-Linked Graphene Oxide-Gelatin Hydrogel for Cartilage Reconstructive Surgery.

Herein, we report the cartilage tissue engineering application of nanographene oxide (NGO)-reinforced gelatin hydrogel fabricated by utilizing a microplasma-assisted cross-linking method. NGO sheets with surface functionalities were introduced to enhance the mechanical and biomedical properties of gelatin-based hydrogels. Highly energetic reactive radicals were generated from the nonthermal plasma (NTP), which is used to facilitate the cross-linking and polymerization during the polymeric hydrogel fabrication. The NTP treatment substantially reinforced a small amount (1 wt %) of NGO into the gelatin hydrogel. Systematic material characterization thus shows that the fabricated hydrogel possessed unique properties such as moderate surface roughness and adhesiveness, suitable pores sizes, temperature-dependent viscoelasticity, and controllable degradability. In vitro studies demonstrated that the as-fabricated hydrogel exhibited excellent cell-material interactions with SW 1353 cells, bone marrow-derived mesenchymal stem cells, and a rat chondrocyte cell line, thereby exhibiting appropriate cytocompatibility for cartilage tissue engineering applications. Furthermore, an in vivo study indicated that the formation of a healthy hyaline cartilage after the microfracture was enhanced by the fabricated hydrogel implant, offering a potential biocompatible platform for microfracture-based cartilage reconstructive surgery.

Effect of Hydroxyapatite Formation on Titanium Surface with Bone Morphogenetic Protein-2 Loading through Electrochemical Deposition on MG-63 Cells.

Calcium phosphate ceramics used in dentistry and orthopedics are some of the most valuable biomaterials, owing to their excellent osteoconduction, osteoinduction, and osseointegration. Osteoconduction and osteoinduction are critical targets for bone regeneration, and osseointegration is essential for any dental implantations. In this study, a hydroxyapatite (HAp) hybrid coating layer with the sequential release of bone morphogenetic protein 2 (BMP-2) was deposited onto an etched titanium substrate by electrochemical deposition. The resulting release of BMP-2 from Ti⁻HAp was assessed by immersing samples in a simulated buffer fluid solution. Through coculture, human osteosarcoma cell proliferation and alkaline phosphatase activity were assessed. The characteristics and effect on cell proliferation of the hybrid coatings were investigated for their functionality through X-ray diffraction (XRD) and cell proliferation assays. Findings revealed that -0.8 V vs. Ag/AgCl (3 M KCl) exhibited the optimal HAp properties and a successfully coated HAp layer. XRD confirmed the crystallinity of the deposited HAp on the titanium surface. Ti-0.8 V Ti⁻HAp co-coating BMP sample exhibited the highest cell proliferation efficiency and was more favorable for cell growth. A successful biocompatible hybrid coating with optimized redox voltage enhanced the osseointegration process. The findings suggest that this technique could have promising clinical applications to enhance the healing times and success rates of dental implantation.