Objective
To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non‐systemic polyarthritis, sacroiliitis, or enthesitis.
Methods
The Patient/Population, ...Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions.
Results
Thirty‐nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease‐modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies.
Conclusion
This guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision‐making process that accounts for patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
Bone and tissue adhesives are essential in surgeries for wound healing, hemostasis, tissue reconstruction, and drug delivery. However, there are very few degradable materials with high adhesion ...strengths that degrade into bioresorbable byproducts. Caddisfly adhesive silk is interesting due to the presence of phosphoserines, which are thought to afford adhesive properties. In this work, phosphoserine–valine poly(ester urea) copolymers with 2% and 5% phosphoserine content were synthesized to mimic caddisfly adhesive silk. Significantly, the materials are ethanol soluble and water insoluble, making them clinically relevant. Their physical properties were quantified, and the adhesion properties were studied on aluminum and bovine bone substrates before and after cross-linking with Ca2+ ions. The adhesive strength of the phosphorylated copolymer on a bone substrate after cross-linking with Ca2+ was 439 ± 203 kPa, comparable to commercially available PMMA bone cement (530 ± 133 kPa).
Key hurdles for replacing damaged cartilage with an equivalent synthetic construct are the development of a hydrogel with a strength that exceeds that of cartilage and fixation of this hydrogel onto ...the surface of an articulating joint. This article describes the first hydrogel with a tensile and compressive strength (51 and 98 MPa) that exceeds those of cartilage (40 and 59 MPa), and the first attachment of a hydrogel to a metal backing with a shear strength (2.0 MPa) that exceeds that of cartilage on bone (1.2 MPa). The hydrogel strength is achieved through reinforcement of crystallized polyvinyl alcohol with bacterial cellulose. The high attachment strength is achieved by securing freeze‐dried bacterial cellulose to a metal backing with an adhesive and a shape memory alloy clamp prior to infiltration and crystallization of the polyvinyl alcohol. The bacterial cellulose‐reinforced polyvinyl alcohol is three times more wear resistant than cartilage over one million cycles and exhibits the same coefficient of friction. These advances in hydrogel strength and attachment enable the creation of a hydrogel‐based implant for durable resurfacing of damaged articulating joints.
This article describes the first hydrogel with a tensile and compressive strength that exceeds those of cartilage and the first attachment of a hydrogel to a metal backing with a shear strength that exceeds that of cartilage on bone. These advances in hydrogel strength and attachment enable the creation of a hydrogel‐based implant for durable resurfacing of damaged articulating joints.
Resorbable, implantable bioelectronic devices are emerging as powerful tools to reliably monitor critical physiological parameters in real time over extended periods. While degradable magnesium-based ...electronics have pioneered this effort, relatively short functional lifetimes have slowed clinical translation. Barrier films that are both flexible and resorbable over predictable timelines would enable tunability in device lifetime and expand the viability of these devices. Herein, we present a library of stereocontrolled succinate-based copolyesters which leverage copolymer composition and processing method to afford tunability over thermomechanical, crystalline, and barrier properties. One copolymer composition within this library has extended the functional lifetime of transient bioelectronic prototypes over existing systems by several weeks-representing a considerable step towards translational devices.
Amino acid-based poly(ester urea) (PEU) copolymers functionalized with pendant catechol groups that address the need for strongly adhesive yet degradable biomaterials have been developed. Lap-shear ...tests with aluminum adherends demonstrated that these polymers have lap-shear adhesion strengths near 1 MPa. An increase in lap-shear adhesive strength to 2.4 MPa was achieved upon the addition of an oxidative cross-linker. The adhesive strength on porcine skin adherends was comparable with commercial fibrin glue. Interfacial energies of the polymeric materials were investigated via contact angle measurements and Johnson–Kendall–Roberts (JKR) technique. The JKR work of adhesion was consistent with contact angle measurements. The chemical and physical properties of PEUs can be controlled using different diols and amino acids, making the polymers candidates for the development of biological glues for use in clinical applications.
Biodegradable shape memory elastomers have the potential for use in soft tissue engineering, drug delivery, and device fabrication applications. Unfortunately, few materials are able to meet the ...targeted degradation and mechanical properties needed for long-term implantable devices. In order to overcome these limitations, we have designed and synthesized a series of unsaturated polyurethanes that are elastic, degradable, and nontoxic to cells in vitro. The polymerization included a nucleophilic thiol–yne Michael addition between a urethane-based dipropiolate and a dithiol to yield an α,β-unsaturated carbonyl moiety along the polymer backbone. The alkene stereochemistry of the materials was tuned between 32 and 82% cis content using a combination of an organic base and solvent polarity, which collectively direct the nucleophilic addition. The bulk properties such as tensile strength, modulus, and glass transition temperature can also be tuned broadly, and the hydrogen bonding imparted by the urethane moiety allows for these materials to elicit cyclic shape memory behavior. We also demonstrated that the in vitro degradation properties are highly dependent on the alkene stereochemistry.
The importance of stereochemistry to the function of molecules is generally well understood. However, to date, control over stereochemistry and its potential to influence properties of the resulting ...polymers are, as yet, not fully realized. This Review focuses on the state of the art with respect to how stereochemistry in polymers has been used to influence and control their physical and mechanical properties, as well as begin to control their function. A brief overview of the synthetic methodology by which to access these materials is included, with the main focus directed towards the effect of stereochemistry on mechanical properties, biodegradation and conductivity. In addition, advances in applications of stereodefined polymers for enantioseparation and as supports for catalysts in asymmetric transformations are discussed. Finally, we consider the opportunities that the rich stereochemistry of sustainably sourced monomers might offer in this field. Where possible, we have drawn parallels between design principles in order to identify opportunities and limitations that these approaches may present in their effects on materials properties, performance and function.Changes in the stereochemistry of polymer chains result in changes to the mechanical and physical behaviour of the resulting materials. By harnessing synthetic methods to create stereocontrolled polymers, a new parameter can be accessed to control the behaviour of bulk material.
Hydrogel microparticles (HMPs) have been investigated widely for their use in tissue engineering and drug delivery applications. However, translation of these highly tunable systems has been hindered ...by covalent cross-linking methods within microparticles. Stereocomplexation, a stereospecific form of physical cross-linking, provides a robust yet degradable alternative for creating translationally relevant HMPs. Herein, 4-arm polyethylene glycol (PEG) stars were used as macromolecular initiators from which oligomeric poly(l-lactic acid) (PLLA) was polymerized with a degree of polymerization (DPn) of 20 on each arm. Similarly, complementary propargyl-containing ABA cross-linkers with enantiomeric poly(d-lactic acid) (PDLA) segments (DPn = 20) on each arm. Droplets of these gel precursors were formed via a microfluidic organic-in-oil-in-water system where microparticles self-assembled via stereocomplexation and were stabilized after precipitation in deionized water. By varying the flow rate of the dispersed phase, well-defined microparticles with diameters of 33.7 ± 0.5, 62.4 ± 0.6, and 105.7 ± 0.8 μm were fabricated. Gelation due to stereocomplexation was confirmed via wide-angle X-ray scattering in which HMPs exhibited the signature diffraction pattern of stereocomplexed PLA at 2θ = 12.2, 21.2, 24.2°. Differential scanning calorimetry also confirmed stereocomplexation by the appearance of a crystallization exotherm (T c = 37 °C) and a high-temperature endotherm (T m = 159 °C) that does not appear in the homocrystallization of PLLA or the hydrogel precursors. Additionally, the propargyl handle present on the cross-linker allows for pre- or post-assembly thiol-yne “click” functionalization as demonstrated by the addition of thiol-containing fluorophores to the HMPs.
Neuroregeneration following peripheral nerve injury is largely mediated by Schwann cells (SC), the principal glial cell that supports neurons in the peripheral nervous system. Axonal regeneration in ...vivo is limited by the extent of SC migration into the gap between the proximal and distal nerve, however, little is known regarding the principal driving forces for SC migration. Engineered microenvironments, such as molecular and protein gradients, play a role in the migration of many cell types, including cancer cells and fibroblasts. However, haptotactic strategies have not been applied widely to SC. Herein, a series of tethered laminin-derived peptides were analyzed for their influence on SC adhesion, proliferation, and alignment. Concentration gradient substrates were fabricated using a controlled vapor deposition method, followed by covalent peptide attachment via a thiol-ene reaction, and characterized by X-ray photoelectron spectroscopy (XPS) and MALDI-MS imaging. While tethered RGD peptides supported SC adhesion and proliferation, concentration gradients of RGD had little influence on biased SC directional migration. In contrast, YIGSR promoted less SC attachment than RGD, yet YIGSR peptide gradients directed migration with a strong bias to the concentration profile. With YIGSR peptide, overall speed increased with the steepness of the peptide concentration profile. YIGSR gradients had no haptotactic effect on rat dermal fibroblast migration, in contrast to fibroblast migration on RGD gradients. The response of SC to these tethered peptide gradients will guide the development of translationally relevant constructs designed to facilitate endogenous SC infiltration into defects for nerve regeneration.
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