Fibrinogen-based cell and spheroid sheets manipulating and delivery for mouse hindlimb ischemia.

In this research, we introduced a novel strategy for fabricating cell sheets (CSs) prepared by simply adding a fibrinogen solution to growth medium without using any synthetic polymers or chemical agents. We confirmed that the fibrinogen-based CS could be modified for target tissue regardless of size, shape, and cell types. Also, fibrinogen-based CSs were versatile and could be used to form three-dimensional (3D) CSs such as multi-layered CSs and those mimicking native blood vessels. We also prepared fibrinogen-based spheroid sheets for the treatment of ischemic disease. The fibrinogen-based spheroid sheets had much higherin vitrotubule formation and released more angiogenic factors compared to other types of platform in this research. We transplanted fibrinogen-based spheroid sheets into a mouse hindlimb ischemia model and found that fibrinogen-based spheroid sheets showed significantly improved physiological function and blood perfusion rates compared to the other types of platform in this research.

Rationally designed bioactive milk-derived protein scaffolds enhanced new bone formation.

Recently, a number of studies reported that casein was composed of various multifunctional bioactive peptides such as casein phosphopeptide and ß-casochemotide-1 that bind calcium ions and induce macrophage chemotaxis, which is crucial for bone homeostasis and bone fracture repair by cytokines secreted in the process. We hypothesized that the effects of the multifunctional biopeptides in casein would contribute to improving bone regeneration. Thus, we designed a tissue engineering platform that consisted of casein and polyvinyl alcohol, which was a physical-crosslinked scaffold (milk-derived protein; MDP), via simple freeze-thaw cycles and performed surface modification using 3,4-dihydroxy-l-phenylalanine (DOPA), a mussel adhesive protein, for immobilizing adhesive proteins and cytokines for recruiting cells in vivo (MDP-DOPA). Both the MDP and MDP-DOPA groups proved indirectly contribution of macrophages migration as RAW 264.7 cells were highly migrated toward materials by contained bioactive peptides. We implanted MDP and MDP-DOPA in a mouse calvarial defect orthotopic model and evaluated whether MDP-DOPA showed much faster mineral deposition and higher bone density than that of the no-treatment and MDP groups. The MDP-DOPA group showed the accumulation of host M2 macrophages and mesenchymal stem cells (MSCs) around the scaffold, whereas MDP presented mostly M1 macrophages in the early stage.

Enhanced extraction of skin interstitial fluid using a 3D printed device enabling tilted microneedle penetration.

Interstitial fluid (ISF) is a body fluid that fills, surrounds cells and contains various biomarkers, but it has been challenging to extract ISF in a reliable and sufficient amount with high speed. To address the issues, we developed the tilted microneedle ISF collecting system (TMICS) fabricated by 3D printing. In this system, the microneedle (MN) was inserted at 66° to the skin by TMICS so that the MN length could be extended within a safe range of skin penetration. Moreover, TMICS incorporating three MN patches created reliable ISF collecting conditions by penetrating the skin at consistent angle and force, 4.9 N. Due to the MN length increase and the patch number expansion, the surface area of the penetrated tissue was increased, thereby confirming that ISF extraction efficiency was improved. Skin ISF was collected into the paper reservoir on the patch, and the absorbed area was converted into a volume. ISF extraction from the rat skin in vivo by TMICS was well tolerated, and the 2.9 µL of ISF was obtained within 30 s. Therefore, TMICS is promising to apply in the diagnosis of multiple biomarkers in ISF with high speed and stability.

Nanozyme Impregnated Mesenchymal Stem Cells for Hepatic Ischemia-Reperfusion Injury Alleviation.

Mesenchymal stem cell (MSC) based therapy holds great potential for treating numerous diseases owing to their capability to heal injured tissue/organs through paracrine factors secretion and immunomodulation. Despite the high hopes, the low viability of transplanted cells in the injured tissues due to the elevated oxidative stress levels remains the largest obstacle in MSC-based cell therapy. To achieve desired therapeutic efficiency, the survival of the transplanted MSCs in the high oxidative stress environment needs to be ensured. Herein, we proposed the use of a ROS-scavenging nanozyme to protect transplanted MSCs from oxidative stress-mediated apoptosis and thereby improve the therapeutic effect. Prussian blue (PB) nanoparticles as a biocompatible ROS-scavenging nanozyme were incorporated into the MSCs without affecting the stemness and differentiation potential of MSCs. The nanozyme impregnation significantly improved the survival of MSCs in a high oxidative stress condition as well as augmented their paracrine effect and anti-inflammatory properties, resulting in a profound therapeutic effect in vivo in the liver ischemia-reperfusion (I/R) injury animal model. Our results indicated that the nanozyme incorporation into MSCs is a simple but efficient way to improve the therapeutic potential of MSC-based cell therapy.

Deep Learning Application in Spinal Implant Identification.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: To demonstrate the clinical usefulness of deep learning by identifying previous spinal implants through application of deep learning. SUMMARY OF BACKGROUND DATA: Deep learning has recently been actively applied to medical images. However, despite many attempts to apply deep learning to medical images, the application has rarely been successful. We aimed to demonstrate the effectiveness and usefulness of deep learning in the medical field. The goal of this study was to demonstrate the clinical usefulness of deep learning by identifying previous spinal implants through application of deep learning. METHODS: For deep learning algorithm development, radiographs were retrospectively obtained from clinical cases in which the patients had lumbar spine one-segment instrument surgery. A total of 2894 lumbar spine anteroposterior (AP: 1446 cases) and lateral (1448 cases) radiographs were collected. Labeling work was conducted for five different implants. We conducted experiments using three deep learning algorithms. The traditional deep neural network model built by coding the transfer learning algorithm, Google AutoML, and Apple Create ML. Recall (sensitivity) and precision (specificity) were measured after training. RESULTS: Overall, each model performed well in identifying each pedicle screw implant. In conventional transfer learning, AP radiography showed 97.0% precision and 96.7% recall. Lateral radiography showed 98.7% precision and 98.2% recall. In Google AutoML, AP radiography showed 91.4% precision and 87.4% recall; lateral radiography showed 97.9% precision and 98.4% recall. In Apple Create ML, AP radiography showed 76.0% precision and 73.0% recall; lateral radiography showed 89.0% precision and 87.0% recall. In all deep learning algorithms, precision and recall were higher in lateral than in AP radiography. CONCLUSION: The deep learning application is effective for spinal implant identification. This demonstrates that clinicians can use ML-based deep learning applications to improve clinical practice and patient care.Level of Evidence: 3.

Antioxidant and anti-inflammatory activities of Prussian blue nanozyme promotes full-thickness skin wound healing.

Excessive reactive oxygen species (ROS) and unresolved inflammations are the major causes of impaired wound healing as they overwhelm the cellular antioxidant system and impede the healing process. In this study, we examined the application of Prussian blue (PB) nanozyme as a novel material for cutaneous wound healing through the alleviation of excessive ROS and inflammation modulation. The PB nanoparticles not only exhibited hydrogen peroxide (H2O2) degradation activity but also showed strong superoxide scavenging ability. PB nanozyme mitigated the intracellular ROS at a high oxidative stress environment, resulting in a pronounced cytoprotective effect. Moreover, PB nanozyme also displayed significant anti-inflammatory activity, as evident from the suppression of inflammatory mediators in the lipopolysaccharide (LPS) induced macrophage cells. Encouraged by the in vitro results, we evaluated the in vivo therapeutic efficacy of PB nanozyme in a full-thickness cutaneous wound model combined with LPS treatment to mimic bacterial infection. The beneficial effects of topically applied PB nanozyme on wound healing and tissue regeneration were evident compared to the control. The periodical administration of a low amount (50 µg × 4) of PB nanoparticles exhibited faster wound closure as well as collagen deposition, maturation, and organization. Moreover, the PB treatment effectively induced the differentiation of keratinocytes, enhanced the neovascularization, and reduced macrophage burden in the entire wound site. Thus, PB nanozyme not only accelerated the healing process in an infection-mimicking cutaneous wound model but also exhibited tissue regeneration characteristics owing to the synergistic effect of ROS-scavenging and anti-inflammatory activities.

In situ pocket-type microcarrier (PMc) as a therapeutic composite: Regeneration of cartilage with stem cells, genes, and drugs.

We prepared pocket-type micro-carriers (PMc) with pores larger than 30 µm for use in cell delivery by adding 40 mg pluronic F-127 copolymers (F-127) to biodegradable PLGA dissolved in dichloromethane solution. The controlling the size of the pockets in this way facilitates the adhesion of cells by regulating the size of the pockets according to the cells having various sizes. The size of PMc pores could be controlled within a range of 2 to 30 µm by varying the F-127 content. The ratio of F-127 to DOPA-bPEI was most appropriate at 1: 1, and the pocket size at 10 mg/ml of F-127 was appropriate for adhering 20-30 µm stem cells. F-127 containing SOX9 pDNA, in combination with DOPA-polyethylene-coated gold nanoparticles and dexamethasone loaded in PMcs, promoted cartilage differentiation. Gold nanoparticles complex and dexamethasone (DEX) loaded in PMcs were identified by micro-CT imaging and fluorescence imaging, respectively. By captured in pore generated on/in microspheres, the stem cells were safe and stable for use in delivery, both in vitro and in an animal model. Thus, microsphere pores can safely capture stem cells, and at the same time provide a microenvironment in which the captured stem cells can differentiate into chondrocytes.

Osteoconductive hybrid hyaluronic acid hydrogel patch for effective bone formation.

Bio-inspired adhesive hydrogels have been applied to cell and drug delivery systems to address various tissue defects and disorders. However, adhesive hydrogels functionalized with phenolic moieties often lack osteoconductive capacity and mechanical properties for bone regeneration. In this study, we utilized the versatile chemical interactions of phenolic moieties to overcome such limitations in bone tissue engineering efforts. Highly osteoconductive hybrid hydrogel patches were fabricated by incorporating inorganic minerals, hydroxyapatite (HAP), or whitlockite (WKT), into pyrogallol-conjugated hyaluronic acid (HA-PG). The hybrid HA-PG patches exhibited improved mechanical strength and reinforced structural/physical properties owing to additional intermolecular complexation between oxidized PG moieties and ions released from inorganic particles. The sustained release of bone morphogenetic protein-2 (BMP-2) from hybrid patches was prolonged by combination of the inherent nucleophilic affinity of oxidized PG and electrostatic interactions between inorganic particles and BMP-2. With increased osteoconductivity, hybrid patches with HAP or WKT enhanced the osteogenic differentiation of human stem cells while also promoting new bone formation in a critical-sized calvarial defect. Our study demonstrates a translational potential of phenolic adhesive hydrogels engineered with inorganic minerals for orthopedic applications.

Catalytic nanographene oxide with hemin for enhanced photodynamic therapy.

Hypoxia is a hallmark of many malignant solid tumors. The inadequate oxygen concentration in the hypoxic regions of a solid tumor impedes the efficiency of photodynamic therapy (PDT) because the generation of reactive oxygen species during the PDT process is directly dependent on the available oxygen. To enhance the therapeutic efficacy of PDT, we have developed a novel catalytic nanoplatform (nGO-hemin-Ce6) by co-encapsulating hemin as a catalase-mimetic nanozyme and chlorin e6 (Ce6) as a photosensitizer into Pluronic-coated nanographene oxide through simple hydrophobic interaction and π-π stacking. The nanosystem showed high cellular uptake in the breast cancer cells but did not show any cytotoxicity in the dark condition. nGO-hemin-Ce6 showed efficient O2 generation capacity in the presence of H2O2, through the catalase-mimetic activity of hemin. In the in vitro cell experiments, only nGO-hemin-Ce6 could show comparable PDT effect in normoxia as well as hypoxia due to the in situ O2 generation capability. Upon intravenous administration, nGO-hemin-Ce6 nanosystem showed high tumor accumulation through passive targeting owing to their small size (~ 50 nm). Within the tumor, hemin generated O2 from the endogenous H2O2 and attenuated hypoxia as evidenced by the reduced expression of HIF-1α, a prominent hypoxia marker. Meanwhile, catalytically generated O2 markedly improved the therapeutic efficiency of PDT in a mouse tumor xenograft model by aiding the light-induced ROS production by Ce6. Compared to a control nanosystem without hemin (nGOCe6), the catalytic nanosystem of nGO-hemin-Ce6 exhibited significantly higher tumor suppression ability.

Directional Cell Migration Guide for Improved Tissue Regeneration.

The field of tissue regeneration has seen a paradigm shift after one wave of technological innovation after another, which has notably made significant contributions to basic cellular response control and overall tissue regeneration. One particular area that is seeing rekindled interest after technological innovation is managing cell migration toward defects because successful host cell migration from adjacent tissue can accelerate overall regeneration time in tissue defects that are either large in size or irregular in shape. This chapter surveys significant advances on directed cell migration upon topological cues. First, we introduce several examples of patterning and electrospinning technology for guiding directed cell migration, followed by a discussion on approaches to influencing radially aligned topography in pattern or electrospun sheet for overall tissue regeneration.

3D Printer Application for Endoscope-Assisted Spine Surgery Instrument Development: From Prototype Instruments to Patient-Specific 3D Models.

Developing new surgical instruments is challenging. While making surgical instruments could be a good field of application for 3D printers, attempts to do so have proven limited. We designed a new endoscope-assisted spine surgery system, and using a 3D printer, attempted to create a complex surgical instrument and to evaluate the feasibility thereof. Developing the new surgical instruments using a 3D printer consisted of two parts: one part was the creation of a prototype instrument, and the other was the production of a patient model. We designed a new endoscope-assisted spine surgery system with a cannula for the endoscope and working instruments and extra cannula that could be easily added. Using custom-made patient-specific 3D models, we conducted discectomies for paramedian and foraminal discs with both the newly designed spine surgery system and conventional tubular surgery. The new spine surgery system had an extra portal that can be well bonded in by a magnetic connector and greatly expanded the range of access for instruments without unnecessary bone destruction. In foraminal discectomy, the newly designed spine surgery system showed less facet resection, compared to conventional surgery. We were able to develop and demonstrate the usefulness of a new endoscope-assisted spine surgery system relying on 3D printing technology. Using the extra portal, the usability of endoscope-assisted surgery could be greatly increased. We suggest that 3D printing technology can be very useful for the realization and evaluation of complex surgical instrument systems.

Coacervate-mediated exogenous growth factor delivery for scarless skin regeneration.

Although there are numerous medical applications to recover damaged skin tissue, scarless wound healing is being extensively investigated to provide a better therapeutic outcome. The exogenous delivery of therapeutic growth factors (GFs) is one of the engineering strategies for skin regeneration. This study presents an exogenous GF delivery platform developed using coacervates (Coa), a tertiary complex of poly(ethylene argininyl aspartate diglyceride) (PEAD) polycation, heparin, and cargo GFs (i.e., transforming growth factor beta 3 (TGF-ß3) and interleukin 10 (IL-10)). Coa encompasses the advantage of high biocompatibility, facile preparation, protection of cargo GFs, and sustained GF release. We therefore speculated that coacervate-mediated dual delivery of TGF-ß3/IL-10 would exhibit synergistic effects for the reduction of scar formation during physiological wound healing. Our results indicate that the exogenous administration of dual GF via Coa enhances the proliferation and migration of skin-related cells. Gene expression profiles using RT-PCR revealed up-regulation of ECM formation at early stage of wound healing and down-regulation of scar-related genes at later stages. Furthermore, direct injection of the dual GF Coa into the edges of damaged skin in a rat skin wound defect model demonstrated accelerated wound closure and skin regeneration after 3 weeks. Histological evaluation and immunohistochemical staining also revealed enhanced formation of the epidermal layer along with facilitated angiogenesis following dual GF Coa delivery. Based on these results, we conclude that polycation-mediated Coa fabrication and exogenous dual GF delivery via the Coa platform effectively augments both the quantity and quality of regenerated skin tissues without scar formation. STATEMENT OF SIGNIFICANCE: This study was conducted to develop a simple administration platform for scarless skin regeneration using polycation-based coacervates with dual GFs. Both in vitro and in vivo studies were performed to confirm the therapeutic efficacy of this platform toward scarless wound healing. Our results demonstrate that the platform developed by us enhances the proliferation and migration of skin-related cells. Sequential modulation in various gene expression profiles suggests a balanced collagen-remodeling process by dual GFs. Furthermore, in vivo histological evaluation demonstrates that our technique enhances clear epidermis formation with less scab and thicker woven structure of collagen bundle, similar to that of a normal tissue. We propose that simple administration of dual GFs with Coa has the potential to be applied as a clinical approach for fundamental scarless skin regeneration.

Oxidative Epigallocatechin Gallate Coating on Polymeric Substrates for Bone Tissue Regeneration.

Plant derived flavonoids have not been well explored in tissue engineering applications due to difficulties in efficient formulations with biomaterials for controlled presentation. Here, the authors report that surface coating of epigallocatechin gallate (EGCG) on polymeric substrates including poly (L-lactic acid) (PLLA) nanofibers can be performed via oxidative polymerization of EGCG in the presence of cations, enabling regulation of biological functions of multiple cell types implicated in bone regeneration. EGCG coating on the PLLA nanofiber promotes osteogenic differentiation of adipose-derived stem cells (ADSCs) and is potent to suppress adipogenesis of ADSCs while significantly reduces osteoclastic maturation of murine macrophages. Moreover, EGCG coating serves as a protective layer for ADSCs against oxidative stress caused by hydrogen peroxide. Finally, the in vivo implantation of EGCG-coated nanofibers into a mouse calvarial defect model significantly promotes the bone regeneration (61.52 ± 28.10%) as compared to defect (17.48 ± 11.07%). Collectively, the results suggest that EGCG coating is a simple bioinspired surface modification of polymeric biomaterials and importantly can thus serve as a promising interface for tuning activities of multiple cell types associated with bone fracture healing.

Accelerated Bone Regeneration via Three-Dimensional Cell-Printed Constructs Containing Human Nasal Turbinate-Derived Stem Cells as a Clinically Applicable Therapy.

Stem cell transplantation is a promising therapeutic strategy that includes both cell therapy and tissue engineering for the treatment of many regenerative diseases; however, the efficacy and safety of stem cell therapy depend on the cell type used in therapeutic and translational applications. In this study, we validated the hypothesis that human nasal turbinate-derived mesenchymal stem cells (hTMSCs) are a potential therapeutic source of adult stem cells for clinical use in bone tissue engineering using three-dimensional (3D) cell-printing technology. hTMSCs were cultured and evaluated for clinical use according to their cell growth, cell size, and preclinical safety and were then incorporated into a multicompositional 3D bioprinting system and investigated for bone tissue regeneration in vitro and in vivo. Finally, hTMSCs were compared with human bone marrow-derived MSCs (hBMSCs), which are the most common stem cell type used in regenerative medicine. hTMSCs from three different donors showed greater and faster cell growth than hBMSCs from two different donors when cultured. The hTMSCs were smaller in size than the hBMSCs. Furthermore, the hTMSCs did not exhibit safety issues in immunodeficient mice. hTMSCs in 3D-printed constructs (3D-hTMSC) showed much greater viability, growth, and osteogenic differentiation potential in vitro than hBMSCs in 3D-printed constructs (3D-hBMSC). Likewise, 3D-hTMSC showed better cell survival and alkaline phosphatase activity and greater osteogenic protein expression than 3D-hBMSC upon subcutaneous implantation into the dorsal region of nude mice. Notably, in an orthotopic model involving implantation into a tibial defect in rats, implantation of 3D-hTMSC led to greater bone matrix formation and enhanced bone healing to a greater degree than implantation of 3D-hBMSC. The clinically reliable evidence provided by these results is underlined by the potential for rapid tissue regeneration and ambulation in bone fracture patients implanted with 3D-hTMSC.

Biodegradable Nerve Guidance Conduit with Microporous and Micropatterned Poly(lactic-co-glycolic acid)-Accelerated Sciatic Nerve Regeneration.

An innovative technique combining capillary force lithography and phase separation method in one step is applied to fabricate artificial nerve guidance conduit (NGC) for peripheral nerve regeneration. Biodegradable porous, patterned NGC (PP-NGC) using poly(lactic-co-glycolic acid) is fabricated. It has micro-grooves and microporosity on the inner surface to promote axonal outgrowth and to enhance permeability for nutrient exchange. In this study, it is confirmed that the inner surface of micro-grooves can modulate neurite orientation and length of mouse neural stem cell compared to porous flat NGC (PF-NGC) in vitro. Coating with 3,4-dihydroxy-l-phenylalanine (DOPA) facilitates the hydrophilic inner surface of PF- and PP-NGCs via bioinspired catechol chemistry. For in vivo study, PF-NGC and PP-NGC coated with or without DOPA are implanted in the 10 mm sciatic nerve defect margins between proximal and distal nerves in rats. Especially, PP-NGC coated with DOPA shows higher sciatic function index score, onset-to-peak amplitude, and muscle fiber diameter compared to other groups. The proposed hybrid-structured NGC not only can serve as a design for functional NGC without growth factor but also can be used in clinical application for peripheral nerve regeneration.

Topographically Defined, Biodegradable Nanopatterned Patches to Regulate Cell Fate and Acceleration of Bone Regeneration.

If only allowed to proceed naturally, the bone-healing process can take several weeks, months, or even years depending on the injury size. In terms of bone-healing speed, many studies have been conducted investigating the deliverance of various growth factors of implantable biomaterials to shorten the time for bone regeneration. However, there may be side effects such as nerve pain, infection, or ectopic bone formation. As an alternative method, we focused on biophysical guidance, which provided similar topographical cues to the cellular environment to recruit host cells for bone defect healing. In this study, we hypothesized that aligned nanotopographical features have enhanced osteoblast recruitment, migration, and differentiation without external stimuli. We designed and fabricated a biodegradable poly(lactic- co-glycolic acid) nanopatterned patch using simple solvent casting and capillary force lithography. We confirmed that a biodegradable nanopatterned patch (BNP) accelerated the migration of osteoblasts according to the orientation of the patterned direction. These highly aligned osteoblasts may contribute to in vitro osteogenic differentiation, such as alkaline phosphate activity, mineralization, and calcium deposition, compared to the biodegradable flat patch (BFP). To demonstrate bone defect healing by BNP guidance in vivo, we implanted either whole or bridge BNP on the critical size defect of mouse calvarial ( ø 4 mm) or tibia bone (3 × 7 mm2). Only the BNP-treated group showed faster new bone formation and compact bone regeneration at the calvarial or tibia bone defect area compared to BFP at 4 or 8 weeks. Bridge BNP guided, in particular, the regeneration of new bone formation along the parallel direction of nanopatterned substrates. Here, we show that a BNP with biophysical guidance should be suitable for use in bone tissue regeneration through accelerated migration of the intact host cell.

Differentiated osteoblasts derived decellularized extracellular matrix to promote osteogenic differentiation.

BACKGROUND: The extracellular matrix (ECM) can directly or indirectly influence on regulation of cell functions such as cell adhesion, migration, proliferation and differentiation. The cell derived ECM (CD-ECM) is a useful in vitro model for studying the comprehensive functions of CD-ECM because it maintains a native-like structure and composition. In this study, the CD-ECM is obtained and a test is carried out to determine the effectiveness of several combinations of decellularized methods. These methods were used to regulate the optimal ECM compositions to be induced by osteogenic differentiation using primary isolated osteoblasts. RESULT: We investigated the effect of osteoblasts re-seeded onto normal osteoblast ECM under the growth medium (GM-ECM) and the osteogenic differentiation medium (OD-ECM). The osteoblasts were then cultured statically for 1, 2, and 4 weeks in a growth medium or differentiation medium. Before osteoblast culture, we performed immunostaining with filamentous actin and nuclei, and then performed DNA quantification. After each culture period, the osteogenic differentiation of the osteoblasts re-seeded on the OD-ECMs was enhanced osteogenic differentiation which confirmed by alkaline phosphatase staining and quantification, Alizarin Red S staining and quantification, and von Kossa staining. The OD-ECM-4 W group showed more effective osteogenic differentiation than GM-ECM and OD-ECM-2 W. CONCLUSIONS: The OD-ECM-4 W has a better capacity in a microenvironment that supports osteogenic differentiation on the GM-ECM and OD-ECM-2 W. The ECM substrate has a wide range of applications as cell culture system or direct differentiation of stem cell and excellent potential as cell-based tissue repair in orthopedic tissue engineering.

Electrospun Silk Fibroin Nanofibrous Scaffolds with Two-Stage Hydroxyapatite Functionalization for Enhancing the Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells.

The development of functional scaffolds with improved osteogenic potential is important for successful bone formation and mineralization in bone tissue engineering. In this study, we developed a functional electrospun silk fibroin (SF) nanofibrous scaffold functionalized with two-stage hydroxyapatite (HAp) particles, using mussel adhesive-inspired polydopamine (PDA) chemistry. HAp particles were first incorporated into SF scaffolds during the electrospinning process, and then immobilized onto the electrospun SF nanofibrous scaffolds containing HAp via PDA-mediated adhesive chemistry. We obtained two-stage HAp-functionalized SF nanofibrous scaffolds with improved mechanical properties and capable of providing a bone-specific physiological microenvironment. The developed scaffolds were tested for their ability to enhance the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADMSCs) in vitro and repair bone defect in vivo. To boost their ability for bone repair, we genetically modified hADMSCs with the transcriptional coactivator with PDZ-binding motif (TAZ) via polymer nanoparticle-mediated gene delivery. TAZ is a well-known transcriptional modulator that activates the osteogenic differentiation of mesenchymal stem cells (MSCs). Two-stage HAp-functionalized SF scaffolds significantly promoted the osteogenic differentiation of TAZ-transfected hADMSCs in vitro and enhanced mineralized bone formation in a critical-sized calvarial bone defect model. Our study shows the potential utility of SF scaffolds with nanofibrous structures and enriched inorganic components in bone tissue engineering.

Comminuted Radial Head Fracture in All-arthroscopic Repair of Elbow Fracture-dislocation: Is Partial Excision of the Radial Head an Acceptable Treatment Option?

BACKGROUND: In elbow fracture-dislocation, partial excision of the comminuted radial head fracture that is not amenable to fixation remains controversial considering the accompanying symptoms. This study was undertaken to evaluate the results of radial head partial excision when the comminuted radial head fracture involved <50% of the articular surface in all-arthroscopic repair of elbow fracture-dislocation. METHODS: Patients were divided into two groups based on the condition of the radial head fracture. In Group A, the patients had a radial head comminuted fracture involving <50% of the articular surface, and underwent arthroscopic partial excision. Group B was the non-excision group comprising patients with stable and non-displacement fractures. Follow-up consultations were conducted at 6 weeks and at 3, 6, 12, and 24 months after surgery. RESULTS: In all, 19 patients (Group A: 11; Group B: 8) met the inclusion criteria and were enrolled in the study. At the final follow-up, all 19 patients showed complete resolution of elbow instability. No significant differences were observed in the range of motion, visual analogue scale score, and Mayo elbow performance score between groups. Radiological findings did not show any complications of the radiocapitellar joint. However, nonunion of the coracoid fracture was observed in 3 patients (Group A: 1; Group B: 2), without any accompanying instability and clinical symptoms. CONCLUSIONS: Considering that the final outcome is coronoid fracture fixation and lateral collateral ligament complex repair for restoring elbow stability, arthroscopic partial excision for radial head comminuted fractures involving <50% of articular surface is an effective and acceptable treatment for elbow fracture-dislocation.

Sphingosine-1-Phosphate Immobilized on Nanotopographical Scaffolds Improve Myogenic Differentiation.

The skeletal muscle consists of highly aligned dense cables of collagen fibers with nanometer feature size to support muscle fibers. The skeletal myocyte can be greatly affected to differentiate by their surrounding topographical structure. To improve myogenic differentiation, we fabricated cell culture platform that sphingosine-1-phosphate (S1P) which regulated myocyte behavior is immobilized on a biomimetic nanopatterned polyurethaneacrylate (PUA) substrate using 3,4-dihydroxyphenylalanine (L-DOPA) for providing topographical and biological cues synergistically. In the present study, we hypothesized that cultured C2C12 cells can be induced to synergistically promote myogenic differenntiation on nanopatterned PUA-L-DOPA-S1P. We confirmed that nanopatterned PUA-L-DOPA-S1P has high hydrophilicity with a suitable range of water contact angle and small intensity of phosphate peak (P2p) by analyses of water contact analyzer and X-ray photoelectron spectroscopy. In addition, C2C12 cells culured on nanopatterned PUA-L-DOPA-S1P has well-oriented and organized myodubes formed with greater expression of myogenic regulatory factors such as MyoD and MyoG comapred to flat PUA groups. This functional platform which is not only provided topographical and biological cues has a suitable potential function to apply muscle cell niche as similar structure of muscle fiber but also utilized cell behavior within tissue engineered scaffolds and cellular microenvironment.