Person:

Cezar, Christine Anne

Foldable photoelectronics and muscle-like transducers require highly stretchable and transparent electrical conductors. Some conducting oxides are transparent, but not stretchable. Carbon nanotube films, graphene sheets and metal-nanowire meshes can be both stretchable and transparent, but their electrical resistances increase steeply with strain <100%. Here we present highly stretchable and transparent Au nanomesh electrodes on elastomers made by grain boundary lithography. The change in sheet resistance of Au nanomeshes is modest with a one-time strain of ~160% (from ~21 Ω per square to ~67 Ω per square), or after 1,000 cycles at a strain of 50%. The good stretchability lies in two aspects: the stretched nanomesh undergoes instability and deflects out-of-plane, while the substrate stabilizes the rupture of Au wires, forming distributed slits. Larger ratio of mesh-size to wire-width also leads to better stretchability. The highly stretchable and transparent Au nanomesh electrodes are promising for applications in foldable photoelectronics and muscle-like transducers.

Regenerative efforts typically focus on the delivery of single factors, but it is likely that multiple factors regulating distinct aspects of the regenerative process (e.g., vascularization and stem cell activation) can be used in parallel to affect regeneration of functional tissues. This possibility was addressed in the context of ischemic muscle injury, which typically leads to necrosis and loss of tissue and function. The role of sustained delivery, via injectable gel, of a combination of VEGF to promote angiogenesis and insulin-like growth factor-1 (IGF1) to directly promote muscle regeneration and the return of muscle function in ischemic rodent hindlimbs was investigated. Sustained VEGF delivery alone led to neoangiogenesis in ischemic limbs, with complete return of tissue perfusion to normal levels by 3 weeks, as well as protection from hypoxia and tissue necrosis, leading to an improvement in muscle contractility. Sustained IGF1 delivery alone was found to enhance muscle fiber regeneration and protected cells from apoptosis. However, the combined delivery of VEGF and IGF1 led to parallel angiogenesis, reinnervation, and myogenesis; as satellite cell activation and proliferation was stimulated, cells were protected from apoptosis, the inflammatory response was muted, and highly functional muscle tissue was formed. In contrast, bolus delivery of factors did not have any benefit in terms of neoangiogenesis and perfusion and had minimal effect on muscle regeneration. These results support the utility of simultaneously targeting distinct aspects of the regenerative process.

Skeletal muscle comprises a large percentage of the human body mass and plays an essential role in locomotion, postural support, and breathing. Unfortunately, severe muscle injuries can lead to extensive and irreversible fibrosis, scarring, and loss of function without therapeutic intervention. In these cases, the repair of damaged muscle may be improved by a material system capable of on-demand, spatiotemporally controlled biologic delivery. The hypothesis guiding this thesis is that the regeneration of injured skeletal muscle can be controlled by an active ferrogel scaffold that provides a microenvironment suitable for myogenic cell survival and is capable of delivering these cells to injured muscle tissue in a noninvasive and precisely timed manner.

In this thesis, a new magnetically responsive biomaterial capable of triggered drug and cell delivery was developed to enhance the regeneration of severely injured skeletal muscle. By redistributing the iron oxide content of the conventional monophasic ferrogel, biphasic ferrogels were fabricated that were appropriate in size and mechanical properties for in vivo implantation and on-demand triggered release in small animal models. Strikingly, magnetic actuation of empty biphasic ferrogel scaffolds resulted in uniform cyclic compressions that enhanced muscle regeneration without the use of cells or growth factors. Reduced fibrous capsule formation around the implant, as well as reduced fibrosis and inflammation in the injured muscle, demonstrated a potential immunomodulatory role for ferrogel-driven cyclic compressions.

Biphasic ferrogel scaffolds were also used to deliver cells and growth factors precisely timed with inflammation in vivo to enhance functional muscle regeneration. Cells and growth factors were delivered by ferrogel scaffold to severely injured muscle immediately following injury and at delayed time points. Significant reductions in fibrosis and increases in angiogenesis were observed following delayed delivery. More importantly, delayed scaffold treatment of injured muscle led to enhanced engraftment efficiency and functional muscle regeneration. Together, these results demonstrate the therapeutic potential of this new magnetically responsive biomaterial.