Engineering and commercialization of human-device interfaces, from bone to brain

Abstract

Cutting edge developments in engineering of tissues, implants and devices allow for guidance and control of specific physiological structure-function relationships. Yet the engineering of functionally appropriate human-device interfaces represents an intractable challenge in the field. This leading opinion review outlines a set of current approaches as well as hurdles to design of interfaces that modulate transfer of information, i.a. forces, electrical potentials, chemical gradients and haptotactic paths, between endogenous and engineered body parts or tissues. The compendium is designed to bridge across currently separated disciplines by highlighting specific commonalities between seemingly disparate systems, e.g. musculoskeletal and nervous systems. We focus on specific examples from our own laboratories, demonstrating that the seemingly disparate musculoskeletal and nervous systems share common paradigms which can be harnessed to inspire innovative interface design solutions. Functional barrier interfaces that control molecular and biophysical traffic between tissue compartments of joints are addressed in an example of the knee. Furthermore, we describe the engineering of gradients for interfaces between endogenous and engineered tissues as well as between electrodes that physically and electrochemically couple the nervous and musculoskeletal systems. Finally, to promote translation of newly developed technologies into products, protocols, and treatments that benefit the patients who need them most, regulatory and technical challenges and opportunities are addressed on hand from an example of an implant cum delivery device that can be used to heal soft and hard tissues, from brain to bone.

Creating High-Resolution Multiscale Maps of Human Tissue Using Multi-beam SEM

“…The ability to image sub-cellular to tissue-organ scale structures is critical in providing an integrated understanding of physiological mechanisms [2,30,31]. A variety of different imaging modalities are usually required to bridge the gaps amongst various length scales.…”

“…Already, a few recent studies in connectomics have utilized mSEM to render volumetric image data from murine specimens sectioned with a microtome and reconstruct neuronal circuits with single-synapse resolution [14]. Multiscale imaging of interfaces between musculoskeletal tissue compartments could reveal precise architectures of tight junctions that control functional barrier properties, which exert profound effects on human physiology [1,2,12,32]. …”

“…Recent advances in coupled, multiscale imaging and modeling of biological systems promise to transform the fields of physiology and medicine [1,2]. Within that context, bridging across length scales presents a fundamental challenge [3–5].…”

“…Multi-beam SEM is capable of reducing acquisition time by more than one order of magnitude and, therefore, of imaging larger surface areas with remarkable resolution [11], paving the path for seamless multiscale imaging of organ systems down to the cellular and even molecular scale [12]. As a consequence, this technology has drawn interest within the scientific community, particularly in areas related to brain connectomics [13,14] and cross-scale musculoskeletal mechanobiology [2,10]. Already, a few recent studies in connectomics have utilized mSEM to render volumetric image data from murine specimens and reconstruct neuronal circuits with single-synapse resolution [13,14].…”

From intricate to integrated: Biofabrication of articulating joints

“…Apart from building gradient structures, constructs comprising of a bone and cartilage region can be a simplified mimicry of the native osteochondral unit . One method would be depositing layers of the same material to ensure proper axial binding, supplementing it with biofunctional compounds to tune cell behavior in each region.…”