Order-Disorder Balance in Silk-Elastin-like Polypeptides Determines Their Self-Assembly into Hydrogel Networks.

The biofabrication of recombinant structural proteins with a range of mechanical or structural features usually relies on the generation of protein libraries displaying variations in terms of amino acid composition, block structure, molecular weight, or physical/chemical cross-linking sites. This approach, while highly successful in generating a wealth of knowledge regarding the links between design features and material properties, has some inherent limitations related to its low throughput. This slows down the pace of the development of recombinant structural proteins.

Drug retention after intradiscal administration.

Intradiscal drug delivery is a promising strategy for treating intervertebral disk degeneration (IVDD). Local degenerative processes and intrinsically low fluid exchange are likely to influence drug retention. Understanding their connection will enable the optimization of IVDD therapeutics.

Qualitative and quantitative characterization of elastin-like polypeptides combining low-PH/low-temperature bottom-up and intact protein liquid chromatography mass spectrometric analysis.

Rationale: Elastin-like polypeptides (ELPs) are elastic and thermoresponsive biopolymers composed of VPGXG repeats (X can be any amino acid except proline), used in biomedical applications, for example, tissue engineering and drug delivery. As different variants of ELP are mostly produced fermentatively, there is a need for the development of analysis methods that allow for absolute protein quantification in both complex matrices and purified samples and MW determination of the final products.

Methods: ELPs were intracellularly expressed in Escherichia coli quantified after cell lysis and enzymatic digestion using a proline-specific protease ProAlanase (Promega) at acidic conditions.

In vitro and in vivo evaluation of the osseointegration capacity of a polycarbonate-urethane zirconium-oxide composite material for application in a focal knee resurfacing implant.

Currently available focal knee resurfacing implants (FKRIs) are fully or partially composed of metals, which show a large disparity in elastic modulus relative to bone and cartilage tissue. Although titanium is known for its excellent osseointegration, the application in FKRIs can lead to potential stress-shielding and metal implants can cause degeneration of the opposing articulating cartilage due to the high resulting contact stresses. Furthermore, metal implants do not allow for follow-up using magnetic resonance imaging (MRI).

Sequence Control of the Self-Assembly of Elastin-Like Polypeptides into Hydrogels with Bespoke Viscoelastic and Structural Properties.

The biofabrication of structural proteins with controllable properties via amino acid sequence design is interesting for biomedicine and biotechnology, yet a complete framework that connects amino acid sequence to material properties is unavailable, despite great progress to establish design rules for synthesizing peptides and proteins with specific conformations (e.g., unfolded, helical, β-sheets, or β-turns) and intermolecular interactions (e.

Surface texture analysis of different focal knee resurfacing implants after 6 and 12 months in vivo in a goat model.

The clinical success of osteochondral implants depends significantly on their surface properties. In vivo, an implant may roughen over time which can decrease its performance. The present study investigates whether changes in the surface texture of metal and two types of polycarbonate urethane (PCU) focal knee resurfacing implants (FKRIs) occurred after 6 and 12 months of in vivo articulation with native goat cartilage.

Prospective Evaluation of Local Sustained Release of Celecoxib in Dogs with Low Back Pain.

Back pain affects millions globally and in 40% of the cases is attributed to intervertebral disc degeneration. Oral analgesics are associated with adverse systemic side-effects and insufficient pain relief. Local drug delivery mitigates systemic effects and accomplishes higher local dosing.

Structure-Property Relationships of Elastin-like Polypeptides: A Review of Experimental and Computational Studies.

Elastin is a structural protein with outstanding mechanical properties (e.g., elasticity and resilience) and biologically relevant functions (e.

Intra-Articular Slow-Release Triamcinolone Acetonide from Polyesteramide Microspheres as a Treatment for Osteoarthritis.

Osteoarthritis (OA) is a common cause of pain and disability. Local corticosteroid injections are effective in treating OA pain and inflammation but are short-acting. Prolonged intra-articular (IA) corticosteroid exposure may even lead to cartilage deterioration.

In vitro and in vivo study on the osseointegration of BCP-coated versus uncoated nondegradable thermoplastic polyurethane focal knee resurfacing implants.

Focal knee resurfacing implants (FKRIs) are intended to treat cartilage defects in middle-aged patients. Most FKRIs are metal-based, which hampers follow-up of the joint using magnetic resonance imaging and potentially leads to damage of the opposing cartilage. The purpose of this study was to develop a nondegradable thermoplastic polyurethane (TPU) FKRI and investigate its osseointegration.

Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing.

Background And Purpose: Corticosteroids are intra-articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial-based sustained delivery may prolong reduction of inflammatory pain, while avoiding harmful peak drug concentrations.

Experimental Approach: The applicability of prolonged corticosteroid exposure was examined in a rat model of anterior cruciate ligament and medial meniscus transection (ACLT + pMMx) with ensuing degenerative changes.

Safety of intradiscal delivery of triamcinolone acetonide by a poly(esteramide) microsphere platform in a large animal model of intervertebral disc degeneration.

Background Context: Local corticosteroids have been used to relieve symptoms of chronic low back pain, although treatment effects have been shown to wear off relatively fast. Prolonging corticosteroid presence by controlled release from biomaterials may allow for longer pain relief while circumventing adverse effects such as high bolus dosages.

Purpose: The purpose of this study was to evaluate the safety and efficacy of intradiscal controlled release of triamcinolone acetonide (TAA) by poly(esteramide) microspheres in a canine degenerated intervertebral disc (IVD) model.

Intra-articular injection of triamcinolone acetonide releasing biomaterial microspheres inhibits pain and inflammation in an acute arthritis model.

Inflammation of the synovium and joint capsule is a main driver of pain in an osteoarthritic (OA) joint. Triamcinolone acetonide (TAA) is a classical corticosteroid that reduces synovitis and alleviates pain, albeit transiently. Biomaterial-based local TAA release may prolong the suppression of pain without the need for multiple injections.

Applicability of a Modified Rat Model of Acute Arthritis for Long-Term Testing of Drug Delivery Systems.

Episodes of inflammation and pain are predominant features of arthritic joint diseases. Drug delivery systems (DDS) could reduce inflammation and pain long-term without chances of infection upon multiple injections. To allow for long-term evaluation of DDS, we modified a previously published acute arthritis model by extending follow-up periods between flare-ups.

Prolonged inhibition of inflammation in osteoarthritis by triamcinolone acetonide released from a polyester amide microsphere platform.

Controlled biomaterial-based corticosteroid release might circumvent multiple injections and the accompanying risks, such as hormone imbalance and muscle weakness, in osteoarthritic (OA) patients. For this purpose, microspheres were prepared from an amino acid-based polyester amide (PEA) platform and loaded with triamcinolone acetonide (TAA). TAA loaded microspheres were shown to release TAA for over 60days in PBS.

Celecoxib-loaded PEA microspheres as an auto regulatory drug-delivery system after intra-articular injection.

In this study, we investigated the potential of celecoxib-loaded polyester amide (PEA) microspheres as an auto-regulating drug delivery system for the treatment of pain associated with knee osteoarthritis (OA). Celecoxib release from PEA microspheres and inflammation responsive release of a small molecule from PEA was investigated in vitro. Inflammation responsive release of a small molecule from PEA was observed when PEA was exposed to cell lysates obtained from a neutrophil-like Hl-60 cell line.

Polymers in Cartilage Defect Repair of the Knee: Current Status and Future Prospects.

Cartilage defects in the knee are often seen in young and active patients. There is a need for effective joint preserving treatments in patients suffering from cartilage defects, as untreated defects often lead to osteoarthritis. Within the last two decades, tissue engineering based techniques using a wide variety of polymers, cell sources, and signaling molecules have been evaluated.

Thermodynamic investigation of Z33-antibody interaction leads to selective purification of human antibodies.

Antibodies, such as IgGs, are widely applied as detection probes, purification ligands and targeting moieties in research and medicine. Protein A from Staphylococcus aureus is capable of selectively binding to antibodies. Z33, a 33 amino acid peptide sequence derived from Protein A, is a minimized binding domain with comparable interaction potential.

A virus-based biocatalyst.

Virus particles are probably the most precisely defined nanometre-sized objects that can be formed by protein self-assembly. Although their natural function is the storage and transport of genetic material, they have more recently been applied as scaffolds for mineralization and as containers for the encapsulation of inorganic compounds. The reproductive power of viruses has been used to develop versatile analytical methods, such as phage display, for the selection and identification of (bio)active compounds.

Fine-tuning the transition temperature of a stimuli-responsive polymer by a simple blending procedure.

Binary mixtures of well-defined, stimuli-responsive elastin-based side-chain polymers show a single transition temperature that depends on blend composition.