In vitro biocompatibility and biomechanics study of novel, Microscopy Aided Designed and ManufacturEd (MADAME) materials emulating natural tissue weaves and their intrinsic gradients.

This study conducted biomechanical and biocompatibility tests of textiles and textile composites, created using recursive logic to emulate the properties of natural tissue weaves and their intrinsic mechanical stiffness gradients. Two sets of samples were created, first to test feasibility on textile samples designed as periosteum substitutes with elastane fibers mimicking periosteum's endogenous elastin and nylon fibers substituting for collagen, and then on composites comprising other combinations of suture materials before and after sterilization. In the first part, the bulk tensile mechanical stiffness of elastane-nylon textiles were tuned through respective fiber composition and orientation, i.e., aligned with and orthogonal to loading direction. Cell culture biocompatibility studies revealed no significant differences in proliferation rates of embryonic murine stem cells seeded on textiles compared to collagen membrane controls. Until the 15th day of culture, cells were rarely observed in direct contact with the elastane fibers, similar to previous observations with elastomeric sheets used in periosteum substitute implants. In the second part of the study textile samples were created from FDA-approved medical sutures comprising silk, expanded polytetrafluoroethylene, and polybutester. Biocompatibility and mechanical stiffness were assessed as a function of sterilization/disinfection mode (steam, ethylene oxide, and serial disinfection with ethanol). Cell proliferation rates did not differ significantly from controls, except for silk-suture containing textiles, which showed bacterial contamination and no viable cells after 15 days' culture for all sterilization methods. Sterilization had mixed (mostly not significant) effects on textile stiffness, except for the case of polybutester suture-based textiles that showed a significant increase in stiffness with ethylene oxide sterilization. In general, all textile combinations exhibited significantly higher stiffness than periosteum. Textiles comprising medical sutures of different stiffnesses arranged in engineered patterns offer a novel means to achieve mechanical gradients in medical device materials, emulating those of nature's own.

Establishing the Basis for Mechanobiology-Based Physical Therapy Protocols to Potentiate Cellular Healing and Tissue Regeneration.

Life is mechanobiological: mechanical stimuli play a pivotal role in the formation of structurally and functionally appropriate body templates through mechanobiologically-driven cellular and tissue re/modeling. The body responds to mechanical stimuli engendered through physical movement in an integrated fashion, internalizing and transferring forces from organ, through tissue and cellular length scales. In the context of rehabilitation and therapeutic outcomes, such mechanical stimuli are referred to as mechanotherapy. Physical therapists use mechanotherapy and mechanical interventions, e.g., exercise therapy and manual mobilizations, to restore function and treat disease and/or injury. While the effect of directed movement, such as in physical therapy, is well documented at the length scale of the body and its organs, a number of recent studies implicate its integral effect in modulating cellular behavior and subsequent tissue adaptation. Yet the link between movement biomechanics, physical therapy, and subsequent cellular and tissue mechanoadaptation is not well established in the literature. Here we review mechanoadaptation in the context of physical therapy, from organ to cell scale mechanotransduction and cell to organ scale extracellular matrix genesis and re/modeling. We suggest that physical therapy can be developed to harness the mechanosensitivity of cells and tissues, enabling prescriptive definition of physical and mechanical interventions to enhance tissue genesis, healing, and rehabilitation.

Engineering mechanical gradients in next generation biomaterials - Lessons learned from medical textile design.

Nonwoven and textile membranes have been applied both externally and internally to prescribe boundary conditions for medical conditions as diverse as oedema and tissue defects. Incorporation of mechanical gradients in next generation medical membrane design offers great potential to enhance function in a dynamic, physiological context. Yet the gradient properties and resulting mechanical performance of current membranes are not well described. To bridge this knowledge gap, we tested and compared the mechanical properties of bounding membranes used in both external (compression sleeves for oedema, exercise bands) and internal (surgical membranes) physiological contexts. We showed that anisotropic compression garment textiles, isotropic exercise bands and surgical membranes exhibit similar ranges of resistance to tension under physiologic strains. However, their mechanical gradients and resulting stress-strain relationships show differences in work capacity and energy expenditure. Exercise bands' moduli of elasticity and respective thicknesses allow for controlled, incremental increases in loading to facilitate healing as injured tissues return to normal structure and function. In contrast, the gradients intrinsic to compression sleeve design exhibit gaps in the middle range (1-5N) of physiological strains and also inconsistencies along the length of the sleeve, resulting in less than optimal performance of these devices. These current shortcomings in compression textile and garment design may be addressed in the future through implementation of novel approaches. For example, patterns, fibre compositions, and fibre anisotropy can be incorporated into biomaterial design to achieve seamless mechanical gradients in structure and resulting dynamic function, which would be particularly useful in physiological contexts. These concepts can be applied further to biomaterial design to deliver pressure gradients during movement of oedematous limbs (compression garments) and facilitate transport of molecules and cells during tissue genesis within tissue defects (surgical membranes). STATEMENT OF SIGNIFICANCE: External and internal biomaterial membranes prescribe boundary conditions for treatment of medical disorders, from oedema to tissue defects. Studies are needed to guide the design of next generation biomaterials and devices that incorporate gradient engineering approaches, which offer great potential to enhance function in a dynamic and physiological context. Mechanical gradients intrinsic to currently implemented biomaterials such as medical textiles and surgical interface membranes are poorly understood. Here we characterise quantitatively the mechanics of textile and nonwoven biomaterial membranes for external and internal use. The lack of seamless gradients in compression medical textiles contrasts with the graded mechanical effects achieved by elastomeric exercise bands, which are designed to deliver controlled, incremental increases in loading to facilitate healing as injured tissues return to normal structure and function. Engineering textiles with a prescient choice of fibre composition/size, type of knit/weave and inlay fibres, and weave density/anisotropy will enable creation of fabrics that can deliver spatially and temporally controlled mechanical gradients to maintain force balances at tissue boundaries, e.g. to treat oedema or tissue defects.

Scale-up of nature's tissue weaving algorithms to engineer advanced functional materials.

We are literally the stuff from which our tissue fabrics and their fibers are woven and spun. The arrangement of collagen, elastin and other structural proteins in space and time embodies our tissues and organs with amazing resilience and multifunctional smart properties. For example, the periosteum, a soft tissue sleeve that envelops all nonarticular bony surfaces of the body, comprises an inherently "smart" material that gives hard bones added strength under high impact loads. Yet a paucity of scalable bottom-up approaches stymies the harnessing of smart tissues' biological, mechanical and organizational detail to create advanced functional materials. Here, a novel approach is established to scale up the multidimensional fiber patterns of natural soft tissue weaves for rapid prototyping of advanced functional materials. First second harmonic generation and two-photon excitation microscopy is used to map the microscopic three-dimensional (3D) alignment, composition and distribution of the collagen and elastin fibers of periosteum, the soft tissue sheath bounding all nonarticular bone surfaces in our bodies. Then, using engineering rendering software to scale up this natural tissue fabric, as well as multidimensional weaving algorithms, macroscopic tissue prototypes are created using a computer-controlled jacquard loom. The capacity to prototype scaled up architectures of natural fabrics provides a new avenue to create advanced functional materials.