An injectable gel based on photo-cross-linkable hyaluronic acid and mesoporous bioactive glass nanoparticles for periodontitis treatment.

Guided bone regeneration (GBR) is an effective strategy to promote periodontal tissue repair. The current study aimed to develop an injectable gel for GBR, composed of photo-cross-linkable hyaluronic acid and mesoporous bioactive glass nanoparticles (MBGNs) loaded with antibacterial minocycline hydrochloride (MNCl). Hyaluronic acid modified with methacrylic anhydride (MHA) that could be cross-linked under UV irradiation was first synthesized. Dynamic rheological evaluation of MHA under UV was carried out to determine its in-situ gelling feasibility and stability. Morphological and mechanical characterization was performed to determine the optimal concentration of MHA gels. Sol-gel derived MBGNs loaded with MNCl were further incorporated into MHA gels to obtain the injectable drug-loaded MBGN-MNCl/MHA gels. In vitro antibacterial, anti-inflammatory and osteogenic effects of this gel were evaluated. It was shown that the MHA gel obtained from 3 % MHA under UV treatment of 30s exhibited a suitable porous structure with a compressive strength of 100 kPa. MBGNs with particle size of ∼120 nm and mesopores were confirmed by TEM and SEM. MBGNs had a loading capacity of ∼120 mg/g for MNCl, exhibiting a sustained release behavior. The MBGN-MNCl/MHA gel was shown to effectively inhibit the proliferation of Streptococcus mutans and the expression of pro-inflammatory factors IL-6 and TNF-α by macrophages. It could on the other hand significantly promote the expression of osteogenic-related genes ALP, Runx2, OPN, and osterix of MC3T3-E1 cells. In conclusion, the current design using photo-crosslinkable MHA gel embedded with MNCl loaded MBGNs can serve as a promising injectable formulation for GBR treatment of irregular periodontal defects.

Modulation of immunosuppressive effect of rapamycin via microfluidic encapsulation within PEG-PLGA nanoparticles.

The high hydrophobicity and low oral availability of immunosuppressive drug, rapamycin, seriously limit its application. It was thus aimed to develop a PEG-PLGA based nano-loading system for rapamycin delivery to achieve improved bioavailability with sustained effects via a novel microfluidic chip and manipulation of the hydrophobic PLGA chain length. PDMS based microfluidic chip with Y shape was designed and PEG-PLGA polymers with different PLGA chain length were used to prepare rapamycin nano-delivery systems. Dendritic cells were selected to evaluate the immunosuppressive effect of the nanoparticles including cytotoxicity assay, dendritic cell activation, and cytokine levels. The effects of different PEG-PLGA nanoparticles on the immunomodulatory properties were finally compared. It was shown that PEG-PLGA could be successfully used for rapamycin encapsulation via microfluidics to obtain nano-delivery systems (Rapa&P-20 k, Rapa&P-50 k and Rapa&P-95 k) ranging from 100 nm to 116 nm. The encapsulation efficiency was ranged from 69.70% to 84.55% and drug loading from 10.45% to 12.68%. The Rapa&P-50 k (PLGA chain length: 50 k) could achieve the highest drug loading (DL) and encapsulation efficiency (EE) as 12.68% and 84.55%. The encapsulated rapamycin could be gradually released from three nanoparticles for more than 1 month without any noticeable burst release. The Rapa & P nanoparticles exhibited enhanced immunosuppressive effects over those of free rapamycin as shown by the expression of CD40 and CD80, and the secretion of IL-1ß, IL-12 and TGF-ß1. Rapa&P-50 k nanoparticles could be the optimal choice for rapamycin delivery as it also achieved the most effective immunosuppressive property. Hence, this study could provide an efficient technology with superior manipulation to offer a solution for rapamycin delivery and clinical application.

Manipulation of porous poly(l-lactide-co-ε-caprolactone) microcarriers via microfluidics for C2C12 expansion.

The growth and repair of skeletal muscle are due in part to activation of muscle precursor cells, commonly known as satellite cells or myoblasts. In order to acquire enough cells for neoskeletal muscle regeneration, it is urgent to develop microcarriers for skeletal myoblasts proliferation with a considerable efficiency. The current study was thus proposed to develop a microfluidic technology to manufacture porous poly(l-lactide-co-ε-caprolactone) (PLCL) microcarriers of high uniformity, and porosity was manipulated via camphene to suit the proliferation of C2C12 cells. A co-flow capillary microfluidic device was first designed to obtain PLCL microcarriers with different porosity. The attachment and proliferation of C2C12 cells on these microcarriers were evaluated and the differentiation potential of expanded cells were verified. The obtained porous microcarriers were all uniform in size with a high mono-dispersity (CV < 5 %). The content of camphene rendered effects on the size, porosity, and pore size of microcarriers, and porous structure addition produced a softening of their mechanical properties. The one of 10 % camphene (PM-10) exhibited the superior expansion for C2C12 cells with the number of cells after 5 days of culture reached 9.53 times of the adherent cells on the first day. The expanded cells from PM-10 still retained excellent myogenic differentiation performance as the expressions of MYOD, Desmin and MYH2 were intensively enhanced. Hence, the current developed porous PLCL microcarriers could offer as a promising type of substrates not only for in vitro muscular precursor cells expansion without compromising any multipotency but also have the potential as injectable constructs to mediate muscle regeneration.

Fabrication and Characterization of Collagen/PVA Dual-Layer Membranes for Periodontal Bone Regeneration.

Guided tissue regeneration (GTR) is a promising treatment for periodontal tissue defects, which generally uses a membrane to build a mechanical barrier from the gingival epithelium and hold space for the periodontal regeneration especially the tooth-supporting bone. However, existing membranes possess insufficient mechanical properties and limited bioactivity for periodontal bone regenerate. Herein, fish collagen and polyvinyl alcohol (Col/PVA) dual-layer membrane were developed via a combined freezing/thawing and layer coating method. This dual-layer membrane had a clear but contact boundary line between collagen and PVA layers, which were both hydrophilic. The dual membrane had an elongation at break of 193 ± 27% and would undergo an in vitro degradation duration of more than 17 days. Further cell experiments showed that compared with the PVA layer, the collagen layer not only presented good cytocompatibility with rat bone marrow-derived mesenchymal stem cells (BMSCs), but also promoted the osteogenic genes (RUNX2, ALP, OCN, and COL1) and protein (ALP) expression of BMSCs. Hence, the currently developed dual-layer membranes could be used as a stable barrier with a stable degradation rate and selectively favor the bone tissue to repopulate the periodontal defect. The membranes could meet the challenges encountered by GTR for superior defect repair, demonstrating great potential in clinical applications.

Adaptive output-feedback control with prescribed performance for trajectory tracking of underactuated surface vessels.

In this paper, we address the problem of trajectory tracking control of underactuated surface vessels in a quantitative method with only position and attitude available. Combined with high-gain observer, parameter compression algorithm and performance function, an adaptive control scheme with prescribed performance is proposed. The high-gain observer is constructed to estimate the velocities, and the parameter compression algorithm is adopted to address persistent perturbations and model uncertainties in a more concise way. By prescribed performance function, the controller can be designed with prescribed performance. The results about system stability is given and proved by using the Lyapunov direct method. The signals concerning with all the errors converge to a bounded set. Compared with the existing methods, the developed scheme can reduce the number of tuning parameters, and guarantee the tracking errors bounded within the prescribed performance constraints in the transformed coordinate, which means the steady errors, convergence rates and maximum overshoots can be guaranteed by the performance function. Comparison and numerical simulations are given to demonstrate the effectiveness of the proposed scheme.