Limb Studies
A Novel, Translatable Platform for Muscular, Nervous, Wound and Bone Research
Pebble's LIVING-LIMB System
The Pebble LIVING-LIMB system replicates in-vivo physiology, circulating warm, nutrient rich, oxygenated blood through arteries and deoxygenated, nutrient depleted blood through veins. This restores metabolic function within the limb, providing an ideal platform for testing therapies and devices in a translatable model. The nerves within the model are preserved and can be precisely isolated for testing nerve-blocking agents and muscle relaxants.
By facilitating the evaluation of immediate immune responses and offering pharmacokinetic and pharmacodynamic profiling, the LIVING-LIMB system guides the development of safer and more effective treatments for clinical use.
Additionally, it supports the refinement of muscle-targeted delivery and personalised dosing strategies, essential for precision medicine. This provides a unique platform for mapping the biodistribution and tropism of therapies, as well as evaluating efficacy.
Perfusion Protocol
The limb is perfused with autologous blood and maintained under physiological conditions.
Our LIVING-LIMB System reproduces the living environment, providing an excellent platform for translatable testing. A warm, oxygenated blood-based perfusate is pumped through the vasculature, providing nutrients and restoring full metabolism and physiology.
We only use clinical gold standard protocols for organ preservation (including FDA approved cold-storage and machine perfusion approaches). All solutions, consumables and hardware are FDA/MHRA/EMA approved.
Our expert multidisciplinary team are highly experienced in the field of perfusion, so if you would like to test your innovation, please get in touch.
Limb Services
- Infection Models: We can create bone infection models using our LIVING-LIMB by introducing bacterial pathogens to simulate bone infections and test the efficacy of antimicrobial agents, antibiotics and antimicrobial coatings on bone tissue.
- Drug Delivery Systems: Systems such as injectable scaffolds, nanoparticles, or microparticles, can be tested on our LIVING-LIMB to assess their ability to deliver therapeutic agents, such as antibiotics, growth factors, or anti-inflammatory drugs, to the bone tissue.
- Drug Screening & Pharmacological Studies: Perform drug screening & pharmacological studies to evaluate the effects of pharmaceutical agents, on bone/muscle metabolism, & remodelling. We can evaluate the safety of potential drug candidates for muscle-related conditions.
- Nerve Inflammation: Test therapies such as anticonvulsants, antidepressants, or analgesics for nerve-related conditions like nerve inflammation.
- Gene Therapies: Test genetic material in ex-vivo muscle tissue for genetic muscle disorders.
- Biophysical Therapies: Test therapies such as electrical stimulation, ultrasound therapy, or mechanical loading on our ex-vivo muscle tissue.
- Nutritional Interventions: We can investigate the effects of different nutrients, supplements or dietary interventions on muscle metabolism.
- Exosome Therapies: Exosomes can be applied to our LIVING-LIMB muscle tissue to evaluate their potential therapeutic effects on muscle regeneration, repair, or modulation of muscle inflammation.
- Immunotherapies: Test the effects of immunomodulatory therapies on muscle tissue inflammation and immune cell infiltration.
- Small Molecule Therapies: Test small molecules or pharmacological agents on our LIVING-LIMB muscle tissue to evaluate their potential therapeutic effects on muscle function, contractility or metabolism.
- Compartment Syndrome Treatments: We can simulate compartment syndrome on our LIVING-LIMB system & test the biochemical & haemodynamic effects of interventions.
- Neuromodulation & Nerve Blockers: Electrical impulses can be used to modulate nerve activity, and nerve blockers can be injected near the sciatic nerve.
- Biocompatible Dressings: Test various types of biocompatible dressings, including hydrogels, foams, films & alginates.
- Skin Substitutes: Test skin substitutes, such as cellulardermal matrices or bioengineered skin constructs.
- Tissue Engineering: We can transplant bioengineered muscle, vein & arterial constructs into our LIVING-LIMB, assessing safety & reperfusion efficiency for transplantation.
- Bone Engineering: Test different types of bone graft materials, such as autografts, allografts, xenografts, & synthetic bone substitutes, to evaluate how they integrate with bone tissue.
- Nerve Conduction Studies (NCS): Assess the speed of electrical signals as they move through nerves.
- Electromyography: Assess the electrical activity of muscles.
- Orthopaedic Implants & Devices: Test orthopaedic implants, including screws, plates rods & joint replacement components to evaluate their biomechanical properties, stability & compatibility with bone tissue.
- Mechanical Loading & Biomechanical Studies: Our LIVING-LIMB system can be subjected to controlled mechanical loading using testing rigs or biomechanical testing machines to study bone strength, stiffness, fatigue behaviour & fracture mechanics under different loading conditions.
- Biomechanics: Simulate exercise & physical therapy interventions in our LIVING-LIMB system via mechanical loading or stretching, allowing evaluation of their effects on muscle adaptation, repair or hypertrophy.
- Wound Debridement Devices: Such devices, including mechanical, enzymatic & surgical debridement tools can be assessed.
- Compression Therapy Devices: Applying controlled pressure to a wound modelled in our LIVING-LIMB system, evaluating the efficacy of compression therapy devices in areas such as tissue perfusion, oedema markers & wound healing.
- Temperature Controlled Devices: Temperature-controlled wound care devices, such as thermal therapy systems or cryotherapy devices, can be used to assess tissue perfusion, inflammation & wound healing processes.
- Negative Pressure Wound Therapy (NPWT): NPWT devices can be used to apply controlled suction to the wound area, assessing their effects on wound closure, tissue perfusion & the formation of granulation tissue.
- Electrical Stimulation Devices: Deliver electrical currents to the wound site using your electrical stimulation device and assess their effects on muscle regeneration & wound healing processes.
- Ultrasound Therapy Devices: Assess tissue perfusion, cellular activity & granulation tissue formation through testing of ultrasound therapy devices.
- Hyperbaric Oxygen Therapy (HBOT) Chambers: HBOT chambers & TONO devices can be tested, delivering high concentrations of oxygen to the wound site, assessing tissue oxygenation, angiogenesis & collagen synthesis.
- Macroscopic Examination: Assess the overall appearance of the limb, including colour, size, shape & any visible abnormalities.
- Histological Analysis: Examine thin slices of muscular tissue under a microscope to evaluate the cellular structure, presence of inflammation, or other pathologies.
- Electrophysiological Studies: Measure electrical properties of nerve cells, such as membrane potential or ion channel activity, to evaluate cellular function & integrity.
- Metabolic Assays: Quantify levels of metabolites or enzymes involved in key metabolic pathways within the limb tissue to assess metabolic activity & integrity.
- Oxygen Consumption Measurement: Determine the rate of oxygen consumption by the tissue as an indicator of metabolic activity & mitochondrial function.
- Immunohistochemistry: Identify & localise specific proteins within muscle tissue revealing the distribution of contractile proteins, structural proteins, or markers of cellular proliferation, inflammation, or regeneration.
- Electron Microscopy: High-resolution imaging of muscle ultrastructure, including sarcomeres, mitochondria, sarcoplasmic reticulum & neuromuscular junctions.
- Morphometric Analysis: Measurements of muscle fibre size, shape & distribution to quantify structural changes associated with muscle growth, atrophy, hypertrophy or degeneration.
- Contractility Testing: Assess contractile properties, including muscle force generation, twitch kinetics, fatigue resistance & response to stimulation.
- Electrophysiological Recording: Evaluate the electrical activity & neuromuscular function of ex-vivo muscle preparations to provide insights into motor unit recruitment, action potential propagation & muscle excitability.
- Calcium Imaging: Monitor intracellular calcium dynamics in muscle cells, providing information about excitation-contraction coupling & calcium handling properties.
- Gene & Protein Expression Analysis: Use quantitative real-time PCR (qPCR) or RNA sequencing to analyse gene expression profiles in muscle tissue. We can quantify mRNA levels for genes involved in muscle development, regeneration, metabolism, or signalling pathways. Equally, we can quantify the expression levels of specific proteins in muscle samples in response to intervention.
Pebble's Customisable Service Package
Why Choose Pebble?
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