Orthodontic Rubber Band-Assisted Endoscopic Submucosal Dissection: An Efficient Method for Treating Superficial Colorectal Tumors.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is a complex operation. Effective traction is crucial. We have successfully used an orthodontic rubber band (ORB) combined with the clip traction method to assist ESD (ORB-ESD). The aim of this retrospective study is to describe the method and to compare the efficacy and safety of ORB-ESD versus conventional ESD in the treatment of superficial colorectal tumors. METHODS: We retrospectively analyzed the data of patients with superficial colorectal tumor (with diameter ≥ 20 mm) who received either ORB-ESD (n = 34) or conventional ESD (n = 90) between January 2019 and September 2020. Propensity score matching (PSM) was used to match the clinical data of 31 pairs of patients in each group. RESULTS: Operation time was significantly shorter for ORB-ESD than for conventional ESD (34.5 minutes vs. 56 minutes, P ≤ 0.001). In the propensity-matched cohorts, the operation time remained significantly shorter in the ORB-ESD patients (35 minutes vs. 50 minutes, P = 0.001). Postoperative adverse events, en bloc resection rate, and R0 resection rate were comparable between the two groups (P > 0.05), both before and after propensity score matching. In the ORB subgroup analysis, the trainee and expert ESD operation times were similar (37 (26-53) vs. 33.5 (26-37) minutes, respectively; P = 0.274). CONCLUSION: ORB-ESD appears to be an effective technique for ESD of colorectal cancer. Our findings need to be confirmed in large prospective multicenter studies.

Photo-cross-linked PDMSstar-PEG hydrogels: synthesis, characterization, and potential application for tissue engineering scaffolds.

Inorganic-organic hydrogels with tunable chemical and physical properties were prepared from methacrylated star polydimethylsiloxane (PDMS(star)-MA) and diacrylated poly(ethylene glycol) (PEG-DA) for use as tissue engineering scaffolds. A total of 18 compositionally unique hydrogels were prepared by photo-cross-linking, varying weight ratios of PEG-DA and PDMS(star)-MA of different molecular weights (M(n)): PEG-DA (M(n) = 3.4k and 6k g/mol) and PDMS(star)-MA (M(n) = 1.8k, 5k, and 7k g/mol). Introduction of PDMS(star)-MA caused formation of discrete PDMS-enriched microparticles dispersed within the PEG matrix. The swelling ratio, mechanical properties in tension and compression, nonspecific protein adhesion, controlled introduction of bioactivity, and cytotoxicity of hydrogels were studied. This library of inorganic-organic hydrogels with tunable properties provides a useful platform to study the effect of scaffold properties on cell behavior.

Biomechanical properties of synthetic and biologic graft materials following long-term implantation in the rabbit abdomen and vagina.

OBJECTIVE: We sought to evaluate the effects of anatomic location and ovariectomy on biomechanical properties of synthetic and biologic graft materials after long-term implantation. STUDY DESIGN: A total of 35 rabbits underwent ovariectomy or sham laparotomy and were implanted with polypropylene (PP) mesh (n = 17) or cross-linked porcine dermis (PS) (n = 18) in the vagina and abdomen. Grafts were harvested 9 months later and underwent mechanical properties testing. RESULTS: After implantation, PS was similar in strength (P = .52) but was twice as stiff as PP (P = .04) and had a maximal elongation only half that of PP (P < .001). Degradation of PS was associated with decreased ultimate tensile strength (P = .03) and elastic modulus (P = .046). Vaginal PP grafts shrunk more (P < .001) and were less stiff than abdominal PP grafts (P = .049) but were not different in strength (P = .19). Ovariectomy had no effect (P > .05). CONCLUSION: Cross-linked PS undergoes long-term degradation resulting in compromised biomechanical properties and thus is likely inferior to lightweight PP meshes for pelvic organ prolapse and incontinence procedures.

Thermoresponsive nanocomposite hydrogels with cell-releasing behavior.

Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels become more hydrophobic when they reversibly switch from a water-swollen to a deswollen state above the volume phase transition temperature (VPTT, approximately 33 degrees C) which has been used to modulate cell adhesion. In the current work, we prepared novel thermoresponsive nanocomposite hydrogels comprised of a PNIPAAm hydrogel matrix and polysiloxane colloidal nanoparticles ( approximately 220 nm average diameter) via in situ photopolymerization of aqueous solutions of NIPAAm monomer, N,N'-methylenebisacrylamide (BIS, crosslinker), photoinitiator and polysiloxane nanoparticles (0.5-2.0 wt% based on solution weight) at approximately 7 degrees C. The VPTT of the nanocomposite hydrogels is not altered versus the pure PNIPAAm hydrogel. Dynamic mechanical analysis and tensile tests revealed that higher nanoparticle content generally produced improved hydrogel mechanical properties. Surfaces of nanocomposite hydrogels became increasingly more hydrophobic at all temperatures between 10 and 40 degrees C as the amount of hydrophobic polysiloxane nanoparticles was increased. When cooled from 37 to 25 degrees C, mouse smooth muscle precursor cells (10T1/2) were effectively detached from nanocomposite hydrogel surfaces. The utility of photopatterning to create surface micropillars comprised of nanocomposite hydrogels was demonstrated.

Influence of hydrogel mechanical properties and mesh size on vocal fold fibroblast extracellular matrix production and phenotype.

Current clinical management of vocal fold (VF) scarring produces inconsistent and often suboptimal results. Researchers are investigating a number of alternative treatments for VF lamina propria (LP) scarring, including designer implant materials for functional LP regeneration. In the present study, we investigate the effects of the initial scaffold elastic modulus and mesh size on encapsulated VF fibroblast (VFF) extracellular matrix (ECM) production toward rational scaffold design. Poly(ethylene glycol) diacrylate (PEGDA) hydrogels were selected for this study since their material properties, including mechanical properties, mesh size, degradation rate and bioactivity, can be tightly controlled and systematically modified. Porcine VFF were encapsulated in four PEGDA hydrogels with degradation half lives of approximately 25 days, but with initial elastic compressive moduli and mesh sizes ranging from approximately 30 to 100kPa and from approximately 9 to 27nm, respectively. After 30 days of static culture, VFF ECM production and phenotype in each formulation was assessed biochemically and histologically. Sulfated glycosaminoglycan synthesis increased in similar degree with both increasing initial modulus and decreasing initial mesh size. In contrast, elastin production decreased with increasing initial modulus but increased with decreasing initial mesh size. Both collagen deposition and the induction of a myofibroblastic phenotype depended strongly on initial mesh size but appeared largely unaffected by variations in initial modulus. The present results indicate that scaffold mesh size warrants further investigation as a critical regulator of VFF ECM synthesis. Furthermore, this study validates a systematic and controlled approach for analyzing VFF response to scaffold properties, which should aid in rational scaffold selection/design.

Visible light crosslinkable chitosan hydrogels for tissue engineering.

In situ gelling constructs, which form a hydrogel at the site of injection, offer the advantage of delivering cells and growth factors to the complex structure of the defect area for tissue engineering. In the present study, visible light crosslinkable hydrogel systems were presented using methacrylated glycol chitosan (MeGC) and three blue light initiators: camphorquinone (CQ), fluorescein (FR) and riboflavin (RF). A minimal irradiation time of 120 s was required to produce MeGC gels able to encapsulate cells with CQ or FR. Although prolonged irradiation up to 600 s improved the mechanical strength of CQ- or FR-initiated gels (compressive modulus 2.8 or 4.4 kPa, respectively), these conditions drastically reduced encapsulated chondrocyte viability to 5% and 25% for CQ and FR, respectively. Stable gels with 80-90% cell viability could be constructed using radiofrequency (RF) with only 40s irradiation time. Increasing irradiation time up to 300s significantly improved the compressive modulus of the RF-initiated MeGC gels up to 8.5 kPa without reducing cell viability. The swelling ratio and degradation rate were smaller at higher irradiation time. RF-photoinitiated hydrogels supported proliferation of encapsulated chondrocytes and extracellular matrix deposition. The feasibility of this photoinitiating system as in situ gelling hydrogels was further demonstrated in osteochondral and chondral defect models for potential cartilage tissue engineering. The MeGC hydrogels using RF offer a promising photoinitiating system in tissue engineering applications.

Osteogenic potential of poly(ethylene glycol)-poly(dimethylsiloxane) hybrid hydrogels.

Growth factors have been shown to be potent mediators of osteogenesis. However, their use in tissue-engineered scaffolds not only can be costly but also can induce undesired responses in surrounding tissues. Thus, the ability to specifically induce osteogenic differentiation in the absence of exogenous growth factors through manipulation of scaffold material properties would be desirable for bone regeneration. Previous research indicates that addition of inorganic or hydrophobic components to organic, hydrophilic scaffolds can enhance multipotent stem cell (MSC) osteogenesis. However, the combined impact of scaffold inorganic content and hydrophobicity on MSC behavior has not been systematically explored, particularly in three-dimensional (3D) culture systems. The aim of the present study was therefore to examine the effects of simultaneous increases in scaffold hydrophobicity and inorganic content on MSC osteogenic fate decisions in a 3D culture environment toward the development of intrinsically osteoinductive scaffolds. Mouse 10T½ MSCs were encapsulated in a series of novel scaffolds composed of varying levels of hydrophobic, inorganic poly(dimethylsiloxane) (PDMS) and hydrophilic, organic poly(ethylene glycol) (PEG). After 21 days of culture, increased levels of osteoblast markers, runx2 and osteocalcin, were observed in scaffolds with increased PDMS content. Bone extracellular matrix (ECM) molecules, collagen I and calcium phosphate, were also elevated in formulations with higher PDMS:PEG ratios. Importantly, this osteogenic response appeared to be specific in that markers for chondrocytic, smooth muscle cell, and adipocytic lineages were not similarly affected by variations in scaffold PDMS content. As anticipated, the increase in scaffold hydrophobicity accompanying increasing PDMS levels was associated with elevated scaffold serum protein adsorption. Thus, scaffold inorganic content combined with alterations in adsorbed serum proteins may underlie the observed cell behavior.

NELL-1 promotes cartilage regeneration in an in vivo rabbit model.

Repair of cartilage due to joint trauma remains challenging due to the poor healing capacity of cartilage and adverse effects related to current growth factor-based strategies. NELL-1 (Nel-like molecule-1; Nel [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]), a protein first characterized in the context of premature cranial suture fusion, is believed to accelerate differentiation along the osteochondral lineage. We previously demonstrated the ability of NELL-1 protein to maintain the cartilaginous phenotype of explanted rabbit chondrocytes in vitro. Our objective in the current study is to determine whether NELL-1 can affect endogenous chondrocytes in an in vivo cartilage defect model. To generate the implant, NELL-1 was incorporated into chitosan nanoparticles and embedded into alginate hydrogels. These implants were press fit into 3-mm circular osteochondral defects created in the femoral condylar cartilage of 3-month-old New Zealand White rabbits (n=10). Controls included unfilled defects (n=8) and defects filled with phosphate-buffered saline-loaded chitosan nanoparticles embedded in alginate hydrogels (n=8). Rabbits were sacrificed 3 months postimplantation for histological analysis. Defects filled with alginate containing NELL-1 demonstrated significantly improved cartilage regeneration. Remarkably, histology of NELL-1-treated defects closely resembled that of native cartilage, including stronger Alcian blue and Safranin-O staining and increased deposition of type II collagen and absence of the bone markers type I collagen and Runt-related transcription factor 2 (Runx2) as demonstrated by immunohistochemistry. Our results suggest that NELL-1 may produce functional cartilage with properties similar to native cartilage, and is an exciting candidate for tissue engineering-based approaches for treating diverse pathologies of cartilage defects and degeneration.

Development of a self-cleaning sensor membrane for implantable biosensors.

Fibrous tissue encapsulation may slow the diffusion of the target analyte to an implanted sensor and compromise the optical signal. Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels are thermoresponsive, exhibiting temperature-modulated swelling behavior that could be used to prevent biofouling. Unfortunately, PNIPAAm hydrogels are limited by poor mechanical strength. In this study, a unique thermoresponsive nanocomposite hydrogel was developed to create a mechanically robust self-cleaning sensor membrane for implantable biosensors. This hydrogel was prepared by the photochemical cure of an aqueous solution of NIPAAm and copoly(dimethylsiloxane/methylvinylsiloxane) colloidal nanoparticles ( approximately 219 nm). At temperatures above the volume phase transition temperature (VPTT) of approximately 33-34 degrees C, the hydrogel deswells and becomes hydrophobic, whereas lowering the temperature below the VPTT causes the hydrogel to swell and become hydrophilic. The potential of this material to minimize biofouling via temperature-modulation while maintaining sensor viability was investigated using glucose as a target analyte. PNIPAAm composite hydrogels with and without poration were compared to a pure PNIPAAm hydrogel and a nonthermoresponsive poly(ethylene glycol) (PEG) hydrogel. Poration led to a substantial increase in diffusion. Cycling the temperature of the nanocomposite hydrogels around the VPTT caused significant detachment of GFP-H2B 3T3 fibroblast cells.