Multi-layer electrospun membrane mimicking tendon sheath for prevention of tendon adhesions.

Defect of the tendon sheath after tendon injury is a main reason for tendon adhesions, but it is a daunting challenge for the biomimetic substitute of the tendon sheath after injury due to its multi-layer membrane-like structure and complex biologic functions. In this study, a multi-layer membrane with celecoxib-loaded poly(l-lactic acid)-polyethylene glycol (PELA) electrospun fibrous membrane as the outer layer, hyaluronic acid (HA) gel as middle layer, and PELA electrospun fibrous membrane as the inner layer was designed. The anti-adhesion efficacy of this multi-layer membrane was compared with a single-layer use in rabbit flexor digitorum profundus tendon model. The surface morphology showed that both PELA fibers and celecoxib-loaded PELA fibers in multi-layer membrane were uniform in size, randomly arrayed, very porous, and smooth without beads. Multi-layer membrane group had fewer peritendinous adhesions and better gliding than the PELA membrane group and control group in gross and histological observation. The similar mechanical characteristic and collagen expression of tendon repair site in the three groups indicated that the multi-layer membrane did not impair tendon healing. Taken together, our results demonstrated that such a biomimetic multi-layer sheath could be used as a potential strategy in clinics for promoting tendon gliding and preventing adhesion without poor tendon healing.

Mesoporous Silicon with Strontium-Powered Poly(Lactic-Co-Glycolic acid)/Gelatin-Based Dressings Facilitate Skin Tissue Repair.

Purpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management. Methods: Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats. Results: The PG@PSiSr membranes can afford the sustained release of silicon ions (Si4+) and strontium ions (Sr2+) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.). Conclusion: To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si4+ and Sr2+, may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines.

Prevention of intra-abdominal adhesion by bi-layer electrospun membrane.

The aim of this study was to compare the anti-adhesion efficacy of a bi-layer electrospun fibrous membrane consisting of hyaluronic acid-loaded poly(ε-caprolactone) (PCL) fibrous membrane as the inner layer and PCL fibrous membrane as the outer layer with a single-layer PCL electrospun fibrous membrane in a rat cecum abrasion model. The rat model utilized a cecal abrasion and abdominal wall insult surgical protocol. The bi-layer and PCL membranes were applied between the cecum and the abdominal wall, respectively. Control animals did not receive any treatment. After postoperative day 14, a visual semiquantitative grading scale was used to grade the extent of adhesion. Histological analysis was performed to reveal the features of adhesion tissues. Bi-layer membrane treated animals showed significantly lower adhesion scores than control animals (p < 0.05) and a lower adhesion score compared with the PCL membrane. Histological analysis of the bi-layer membrane treated rat rarely demonstrated tissue adhesion while that of the PCL membrane treated rat and control rat showed loose and dense adhesion tissues, respectively. Bi-layer membrane can efficiently prevent adhesion formation in abdominal cavity and showed a significantly decreased adhesion tissue formation compared with the control.

Down-regulating ERK1/2 and SMAD2/3 phosphorylation by physical barrier of celecoxib-loaded electrospun fibrous membranes prevents tendon adhesions.

Peritendinous adhesions, as a major problem in hand surgery, may be due to the proliferation of fibroblasts and excessive collagen synthesis, in which ERK1/2 and SMAD2/3 plays crucial roles. In this study, we hypothesized that the complication progression could be inhibited by down-regulating ERK1/2 and SMAD2/3 phosphorylation of exogenous fibroblasts with celecoxib. Celecoxib was incorporated in poly(l-lactic acid)-polyethylene glycol (PELA) diblock copolymer fibrous membranes via electrospinning. Results of an in vitro drug release study showed celecoxib-loaded membrane had excellent continuous drug release capability. It was found that celecoxib-loaded PELA membranes were not favorable for the rabbit fibroblast and tenocyte adhesion and proliferation. In a rabbit tendon repair model, we first identified ERK1/2 and SMAD2/3 phosphorylation as a critical driver of early adhesion formation progression. Celecoxib released from PELA membrane was found to down-regulate ERK1/2 and SMAD2/3 phosphorylation, leading to reduced collagen I and collagen Ⅲ expression, inflammation reaction, and fibroblast proliferation. Importantly, the celecoxib-loaded PELA membranes successfully prevented tissue adhesion compared with control treatment and unloaded membranes treatment. This approach offers a novel barrier strategy to block tendon adhesion through targeted down-regulating of ERK1/2 and SMAD2/3 phosphorylation directly within peritendinous adhesion tissue.

Highly flexible and rapidly degradable papaverine-loaded electrospun fibrous membranes for preventing vasospasm and repairing vascular tissue.

Vasospasm is a common post-operative complication after vascular anastomosis. Currently, the main treatment is a local injection of antispasmodic drugs. However, this method has a high rate of relapse and is subject to a large degree of individual variation, and repeated injections cause additional pain for patients. In this study, we developed highly flexible and rapidly degradable papaverine-loaded electrospun fibrous membranes to be wrapped around vascular suturing to prevent vasospasm. Poly-l-lactic acid/polyethylene glycol (PLLA/PEG) electrospun fibers containing papaverine maintained a high degree of flexibility and could withstand any folding, and are therefore suitable for wrapping vascular suturing. A rapid release of papaverine, between 2 and 7 days, was achieved by adjusting the proportions of PEG and PLLA. PLLA electrospun fibers containing 40% PEG (PLLA-40%) could control drug release and polymer degradation most effectively during the first 2 weeks post-operation. Testing using an in vivo rabbit model showed that PLLA-40% fibrous membranes produced significant antispasmodic effect without observable inflammation or hyperplasia, and the fibrous membranes were ideally biodegradable, with no impact on regional blood flow, pressure, vessel diameter or surrounding tissue hyperplasia. Therefore, papaverine-loaded electrospun fibrous membranes show the potential to greatly reduce post-operative vasospasm and maintain regular vascular morphology during antispasmodic therapy.

[Research progress of mechanism and prevention of peritendinous adhesions].

OBJECTIVE: To review the research progress of mechanism and prevention of peritendinous adhesions. Methods Recent literature about peritendinous adhesions was reviewed, and the results from experiments about the mechanism and prevention of peritendinous adhesions were analyzed. RESULTS: The molecular mechanism of peritendinous adhesions is related to overexpressions of transforming growth factor beta 1, early growth response protein 1, matrix metallopeptidase 9, and so on. The present methods of prevention of peritendinous adhesions include drugs, barrier, optimizing rehabilitation, gene therapy, and so on. These methods have achieved good results in experiments, but the clinical applications have not been confirmed yet. CONCLUSION: It is necessary to pay more attention to the research of mechanism of peritendinous adhesions and methods of its prevention and subsequently to convert them into clinical applications, which is significant to the prevention of peritendinous adhesions in the future.