Synthetic and degradable patches: an emerging solution for rotator cuff repair.

The use of rotator cuff augmentation has increased dramatically over the last 10 years in response to the high rate of failure observed after non-augmented surgery. However, although augmentations have been shown to reduce shoulder pain, there is no consensus or clear guideline as to what is the safest or most efficacious material. Current augmentations, either available commercially or in development, can be classified into three categories: non-degradable structures, extra cellular matrix (ECM)-based patches and degradable synthetic scaffolds. Non-degradable structures have excellent mechanical properties, but can cause problems of infection and loss of integrity in the long-term. ECM-based patches usually demonstrate excellent biological properties in vitro, but studies have highlighted complications in vivo due to poor mechanical support and to infection or inflammation. Degradable synthetic scaffolds represent the new generation of implants. It is proposed that a combination of good mechanical properties, active promotion of biological healing, low infection risk and bio-absorption are the ideal characteristics of an augmentation material. Among the materials with these features, those processed by electrospinning have shown great promis. However, their clinical effectiveness has yet to be proven and well conducted clinical trials are urgently required

Direct electrospinning of poly(vinyl butyral) onto human dermal fibroblasts using a portable device

Objective To demonstrate that uniform poly(vinyl butyral) (PVB) fibres can be safely electrospun onto a monolayer of human dermal fibroblasts using a portable device. Results PVB in solvent mixtures containing various amounts of ethanol and water was electrospun. Six percent (weight-to-volume ratio) PVB in a 9:1 ethanol:water ratio was the solution with the highest content in water that could be electrospun into consistent fibres with an average diameter of 0.9 μm (± 0.1 μm). Four and five percent PVB solutions created beaded fibres. A 8:2 ethanol:water solution lead to microbead formation while a 7:3 ethanol:water mix failed to fully dissolve. The selected solution was successfully electrospun onto a monolayer of human dermal fibroblasts and the process had no significant effect (p < 0.05) on cell viability compared to the control without fibres. Conclusions PVB–ethanol–water solutions could be electrospun without damaging the exposed cell layer. However, further work is required to demonstrate the long-term effect of PVB as a wound healing material

Multifilament electrospun scaffolds for soft tissue reconstruction

While the development of electrospun filaments has remained limited to date, their emergence opens the possibility of creating advanced multifilament scaffolds. Multifilament scaffolds can be designed with sufficient mechanical properties to be used for soft tissue engineering, while still retaining high porosity to encourage cell-mediated repair. This chapter focuses on manufacturing methods for electrospun filaments and postprocessing techniques to improve material properties. The use of textile techniques, such as twisting, braiding, and weaving, in assembling filaments into multifilament yarns is discussed. Finally, electrospun yarns used as multifilament scaffolds for soft tissue repair are explored, with an emphasis on patches and sutures for the anterior cruciate ligament and the rotator cuff. Although most developments have been limited to handmade multifilament yarns, the introduction of semiindustrialized methods for filament electrospinning will likely facilitate translation of multifilament electrospun scaffolds into clinics in the near future.</p

Direct electrospinning of poly(vinyl butyral) onto human dermal fibroblasts using a portable device

Objective To demonstrate that uniform poly(vinyl butyral) (PVB) fibres can be safely electrospun onto a monolayer of human dermal fibroblasts using a portable device. Results PVB in solvent mixtures containing various amounts of ethanol and water was electrospun. Six percent (weight-to-volume ratio) PVB in a 9:1 ethanol:water ratio was the solution with the highest content in water that could be electrospun into consistent fibres with an average diameter of 0.9 μm (± 0.1 μm). Four and five percent PVB solutions created beaded fibres. A 8:2 ethanol:water solution lead to microbead formation while a 7:3 ethanol:water mix failed to fully dissolve. The selected solution was successfully electrospun onto a monolayer of human dermal fibroblasts and the process had no significant effect (p < 0.05) on cell viability compared to the control without fibres. Conclusions PVB–ethanol–water solutions could be electrospun without damaging the exposed cell layer. However, further work is required to demonstrate the long-term effect of PVB as a wound healing material

Effect of annealing on the mechanical properties and the degradation of electrospun polydioxanone filaments

Annealing, or heat treatment, has traditionally been used as a treatment to improve the strength and stiffness of electrospun materials. Understanding the extent to which annealing can improve the mechanical properties and alter the degradation rate of electrospun polydioxanone filaments could influence the range of its potential clinical applications. In this study, we investigated the effect of annealing electrospun polydioxanone filaments at varying times and temperatures and subsequently subjecting them to in vitro degradation in phosphate buffer saline for up to 6 weeks. Fibre alignment, tensile strength and thermal properties were assessed. It was determined that annealing at 65˚C for 3 hours only marginally improved the tensile strength (9±2%) but had a significant effect on reducing strain and rate of degradation, as well as maintaining fibre alignment within the filament. The filament retained significantly more of its force at failure after 4 weeks (82±15%, compared to 61±20% for non annealed filaments) and after 6 weeks of degradation (81±9%, compared to 55±13% for non annealed filaments). Conversely, annealing filaments at 75˚C improved the initial tensile strength of the filament (17±6%), but over 6 weeks, both samples annealed at 75˚C and 85˚C otherwise performed similarly or mechanically worse than those not annealed. These findings suggest that annealing at low temperatures is more useful as a method to tailor degradation rate than to improve mechanical properties. The ability to modulate the degradation profile with annealing may become useful to tailor the properties of electrospun materials without altering the chemistry of the polymer used. This might better match the degradation of the implant and gradual loss of mechanical properties with the new matrix deposition within the structure, enabling multiple regenerative strategies within a single biomaterial system

Physico-chemical characterization of functional electrospun scaffolds for bone and cartilage tissue engineering.

Mimicking the zonal organization of the bone-cartilage interface will aid the production of functional osteochondral grafts for regeneration of skeletal joint defects. This study investigates the potential of the electrospinning technique to build a three-dimensional construct recapitulating the zonal matrix of this interface. Poly(lactic-co-glycolic acid) (PLGA) and PLGA-collagen solutions containing different concentrations of hydroxyapatite nanoparticles (nHAp) were electrospun on a thin layer of phosphate buffer saline solution spread on the collector in order to facilitate membrane detachment and recovery. Incorporation of increasing amounts of nHAp in PLGA solutions did not affect significantly the average diameter of the fibres, which was about 700 nm. However, in the presence of collagen, fibres with diameters below 100 nm were generally observed and the number of these fibres was inversely proportional to the ratio PLGA:collagen and proportional to the content of nHAp. PLGA membranes were rather hydrophobic, although the aqueous drop contact angles progressively fell from 125 degrees to 110 degrees when the content of nHAp was increased from 0 per cent to 50 per cent (w/v). PLGA-collagen membranes were more hydrophilic with contact angles between 60 degrees and 110 degrees; the values being proportional to the ratio PLGA:collagen and the content of nHAp. Also, the addition of nHAp from 0 per cent to 50 per cent (w/v) in the absence of collagen resulted in decreasing dramatically both the Young's modulus (Ym), from 34.3 +/- 1.8 MPa to 0.10 +/- 0.06 MPa, and the ultimate tensile strain (epsilon max), from a value higher than 40 per cent to 5 per cent. However, the presence of collagen together with nHAp allowed the creation of membranes much stiffer, although more brittle, as shown for membranes made with a ratio 8:2 and 10 per cent of nHAp, for which Ym = 70.0 +/- 6.6 MPa and epsilon max = 7 per cent

Multifilament electrospun scaffolds for soft tissue reconstruction

While the development of electrospun filaments has remained limited to date, their emergence opens the possibility of creating advanced multifilament scaffolds. Multifilament scaffolds can be designed with sufficient mechanical properties to be used for soft tissue engineering, while still retaining high porosity to encourage cell-mediated repair. This chapter focuses on manufacturing methods for electrospun filaments and postprocessing techniques to improve material properties. The use of textile techniques, such as twisting, braiding, and weaving, in assembling filaments into multifilament yarns is discussed. Finally, electrospun yarns used as multifilament scaffolds for soft tissue repair are explored, with an emphasis on patches and sutures for the anterior cruciate ligament and the rotator cuff. Although most developments have been limited to handmade multifilament yarns, the introduction of semiindustrialized methods for filament electrospinning will likely facilitate translation of multifilament electrospun scaffolds into clinics in the near future.</p

From chain growth to step growth polymerization of photoreactive poly-ε-caprolactone: the network topology of bioresorbable networks as tool in tissue engineering

Control of the network topology by selection of an appropriate cross-linking chemistry is introduced as a new strategy to improve the elasticity and toughness of bioresorbable networks. The development of novel photocross-linkable and bioresorbable oligomers is essential for the application of light-based 3D-printing techniques in the context of tissue engineering. Although light-based 3D-printing techniques are characterized by an increased resolution and manufacturing speed as compared to extrusion-based 3D-printing, their application remains limited. Via chemical modification, poly-&#x3B5;-caprolactone (PCL) is functionalized with photoreactive end groups such as acrylates, alkenes, and alkynes. Based on these precursors, networks with different topologies are designed via chain growth polymerization, step growth polymerization, or a combination thereof. The influence of the network topology and the concomitant cross-linking chemistry on the thermal, mechanical, and biological properties are elucidated together with their applicability in digital light processing (DLP). Photocross-linkable PCL with an elongation at break of 736.3&#xA0;&#xB1;&#xA0;47% and an ultimate strength of 21.3&#xA0;&#xB1;&#xA0;0.8&#xA0;MPa is realized, which is approximately tenfold higher compared to the current state-of-the-art. Finally, extremely elastic DLP-printed dog bones are developed which can fully retrieve their initial length upon stress relieve at an elongation of 1000%

A layered electrospun and woven surgical scaffold to enhance endogenous tendon repair.

Surgical reattachments of tendon to bone in the rotator cuff are reported to fail in around 40% of cases. There are no adequate solutions to improve tendon healing currently available. Electrospun, sub-micron materials, have been extensively studied as scaffolds for tendon repair with promising results, but are too weak to be surgically implanted or to mechanically support the healing tendon. To address this, we developed a bonding technique that enables the processing of electrospun sheets into multi-layered, robust, implantable fabrics. Here, we show a first prototype scaffold created with this method, where an electrospun sheet was reinforced with a woven layer. The resulting scaffold presents a maximum suture pull out strength of 167N, closely matched with human rotator cuff tendons, and the desired nanofibre-mediated bioactivity in vitro and in vivo. This type of scaffold has potential for broader application for augmenting other soft tissues

Resorbable electrospun polydioxanone fibres modify the behaviour of cells from both healthy and diseased human tendons

Chronic tendinopathy in an active and ageing population represents an increasing burden to healthcare systems. Rotator cuff tendinopathy alone accounts for approximately 70 % of all shoulder pain. Tendinopathic tissue has a disorganised extracellular matrix, altered vasculature, and infiltration of fibroblasts and inflammatory cells. This altered biology may contribute to the limited success of surgical repair strategies. Electrospun resorbable scaffolds can potentially enhance endogenous repair mechanisms by influencing the tissue microenvironment. Polydioxanone (PDO) has an established safety profile in patients. We compared the response of healthy and diseased human tendon cells to electrospun PDO fibres using live cell imaging, proliferation, flow cytometry, and gene expression studies. Within 4 h of initial contact with electrospun PDO, healthy tendon cells underwent a marked transformation; elongating along the fibres in a fibre density dependent manner. Diseased tendon cells initially responded at a slower rate, but ultimately underwent a similar morphological change. Electrospun fibres increased the proliferation rate of diseased tendon cells and increased the ratio of type I:IIIcollagenmRNA expression. Flow cytometry revealed decreased expression of CD106, a marker of mesenchymal stem cells, and increased expression of CD10 on healthy versus diseased tendon cells. PDO electrospun scaffolds further promoted CD106negCD10pos expression of healthy tendon cells. Despite their behavioural differences, both healthy and diseased human tendon cells responded to electrospun PDO fibres. This encourages further work establishing their efficacy in augmenting surgical repair of diseased tendons