Modelling skeletal pain harnessing tissue engineering

Abstract

Bone pain typically occurs immediately following skeletal damage with mechanical distortion or rupture of nociceptive fibres. The pain mechanism is also associated with chronic pain conditions where the healing process is impaired. Any load impacting on the area of the fractured bone will stimulate the nociceptive response, necessitating rapid clinical intervention to relieve pain associated with the bone damage and appropriate mitigation of any processes involved with the loss of bone mass, muscle, and mobility and to prevent death. The following review has examined the mechanisms of pain associated with trauma or cancer-related skeletal damage focusing on new approaches for the development of innovative therapeutic interventions. In particular, the review highlights tissue engineering approaches that offer considerable promise in the application of functional biomimetic fabrication of bone and nerve tissues. The strategic combination of bone and nerve tissue engineered models provides significant potential to develop a new class of in vitro platforms, capable of replacing in vivo models and testing the safety and efficacy of novel drug treatments aimed at the resolution of bone-associated pain. To date, the field of bone pain research has centred on animal models, with a paucity of data correlating to the human physiological response. This review explores the evident gap in pain drug development research and suggests a step change in approach to harness tissue engineering technologies to recapitulate the complex pathophysiological environment of the damaged bone tissue enabling evaluation of the associated pain-mimicking mechanism with significant therapeutic potential therein for improved patient quality of life. Graphical abstract Rationale underlying novel drug testing platform development. Pain detected by the central nervous system and following bone fracture cannot be treated or exclusively alleviated using standardised methods. The pain mechanism and specificity/efficacy of pain reduction drugs remain poorly understood. In vivo and ex vivo models are not yet able to recapitulate the various pain events associated with skeletal damage. In vitro models are currently limited by their inability to fully mimic the complex physiological mechanisms at play between nervous and skeletal tissue and any disruption in pathological states. Robust innovative tissue engineering models are needed to better understand pain events and to investigate therapeutic regimes

Biofabrication of nanocomposite-based scaffolds containing human bone extracellular matrix for the differentiation of skeletal stem and progenitor cells

“…Skeletal tissue engineering (TE) provides functional tools for repairing damaged or diseased bone tissue. Over the last decade, biofabrication approaches for TE have explored a number of biomaterials that support cell delivery and sustain the release of biological agents of interest for the repair [ 1 – 4 ] or the modeling [ 5 ] of bone.…”

Development of a microfluidic-assisted open-source 3D bioprinting system (MOS3S) for the engineering of hierarchical tissues

“…A wide spectrum of applications can be mentioned for 3D printing, from aviation, jewelry, and sculpture to the food [2] and healthcare industry [3] . Recently, the ability of AM in fabricating biologically-relevant structures has captured the interest of engineers and biologists, who have come together to foster the development of 3D bioprinting for tissue fabrication [4] and disease modelling purposes [5] , [6] .…”

“…EBB has enabled the researchers to deposit a wide range of hydrogels of varying viscosities, as well as high cell density; though the resolution of the printed structures is limited to the range of 200–1000 µm [9] . Besides, the EBB method could impose extreme conditions such as high pressure and shear stress on the encapsulated cells, making it detrimental for fabricating cell-laden hydrogels [5] , [10] . Moreover, EBB is currently limited in the printing complexity, resulting capable of generating structures with a single material ink at-a-time [11] .…”

Biofabrication of nanocomposite-based scaffolds containing human bone extracellular matrix for the differentiation of skeletal stem and progenitor cells

“…The sol fraction was calculated using equation ( 2) and (3). Mass swelling ratio (q) was then calculated using equation (4). (3)…”

“…Skeletal tissue engineering (TE) aims to provide functional tools for the repair of damaged or diseased bone tissue. Over the last decade, biofabrication approaches for TE have explored a number of biomaterials able to degrade over time, support cell delivery and sustain the release of biological agents of interest for the repair [1][2][3] or the modelling 4 of bone.…”