Establishment and characterization of a rat model of scalp-cranial composite defect for multilayered tissue engineering.

Composite cranial defects have individual functional and aesthetic ramifications, as well as societal burden, while posing significant challenges for reconstructive surgeons. Single-stage composite reconstruction of these deformities entail complex surgeries that bear many short- and long-term risks and complications. Current research on composite scalp-cranial defects is sparse and one-dimensional, often focusing solely on bone or skin. Thus, there is an unmet need for a simple, clinically relevant composite defect model in rodents, where there is a challenge in averting healing of the skin component via secondary intention. By utilizing a customizable (3D-printed) wound obturator, the scalp wound can be rendered non-healing for a long period (more than 6 weeks), with the cranial defect patent. The wound obturator shows minimal biotoxicity and will not cause severe endocranium-granulation adhesion. This composite defect model effectively slowed the scalp healing process and preserved the cranial defect, embodying the characteristics of a "chronic composite defect". In parallel, an autologous reconstruction model was established as the positive control. This positive control exhibited reproducible healing of the skin within 3 weeks with variable degrees of osseointegration, consistent with clinical practice. Both models provide a stable platform for subsequent research not only for composite tissue engineering and scaffold design but also for mechanistic studies of composite tissue healing.

Polydiolcitrate-MoS2 Composite for 3D Printing Radio-Opaque, Bioresorbable Vascular Scaffolds.

Implantable polymeric biodegradable devices, such as biodegradable vascular scaffolds, cannot be fully visualized using standard X-ray-based techniques, compromising their performance due to malposition after deployment. To address this challenge, we describe a new radiopaque and photocurable liquid polymer-ceramic composite (mPDC-MoS2) consisting of methacrylated poly(1,12 dodecamethylene citrate) (mPDC) and molybdenum disulfide (MoS2) nanosheets. The composite was used as an ink with microcontinuous liquid interface production (µCLIP) to fabricate bioresorbable vascular scaffolds (BVS). Prints exhibited excellent crimping and expansion mechanics without strut failures and, importantly, with X-ray visibility in air and muscle tissue. Notably, MoS2 nanosheets displayed physical degradation over time in phosphate-buffered saline solution, suggesting the potential for producing radiopaque, fully bioresorbable devices. mPDC-MoS2 is a promising bioresorbable X-ray-visible composite material suitable for 3D printing medical devices, such as vascular scaffolds, that require noninvasive X-ray-based monitoring techniques for implantation and evaluation. This innovative biomaterial composite system holds significant promise for the development of biocompatible, fluoroscopically visible medical implants, potentially enhancing patient outcomes and reducing medical complications.

Conducting Polymer Nanoparticles with Intrinsic Aqueous Dispersibility for Conductive Hydrogels.

Conductive hydrogels are promising materials with mixed ionic-electronic conduction to interface living tissue (ionic signal transmission) with medical devices (electronic signal transmission). The hydrogel form factor also uniquely bridges the wet/soft biological environment with the dry/hard environment of electronics. The synthesis of hydrogels for bioelectronics requires scalable, biocompatible fillers with high electronic conductivity and compatibility with common aqueous hydrogel formulations/resins. Despite significant advances in the processing of carbon nanomaterials, fillers that satisfy all these requirements are lacking. Herein, intrinsically dispersible acid-crystalized PEDOT:PSS nanoparticles (ncrys-PEDOTX ) are reported which are processed through a facile and scalable nonsolvent induced phase separation method from commercial PEDOT:PSS without complex instrumentation. The particles feature conductivities of up to 410 S cm-1 , and when compared to other common conductive fillers, display remarkable dispersibility, enabling homogeneous incorporation at relatively high loadings within diverse aqueous biomaterial solutions without additives or surfactants. The aqueous dispersibility of the ncrys-PEDOTX particles also allows simple incorporation into resins designed for microstereolithography without sonication or surfactant optimization; complex biomedical structures with fine features (< 150 µm) are printed with up to 10% particle loading . The ncrys-PEDOTX particles overcome the challenges of traditional conductive fillers, providing a scalable, biocompatible, plug-and-play platform for soft organic bioelectronic materials.

Investigation of 3D Printed Bioresorbable Vascular Scaffold Crimping Behavior.

The rise in additive manufacturing (AM) offers myriad opportunities for 3D-printed polymeric vascular scaffolds, such as customization and on-the-spot manufacturing, in vivo biodegradation, incorporation of drugs to prevent restenosis, and visibility under X-ray. To maximize these benefits, informed scaffold design is critical. Polymeric bioresorbable vascular scaffolds (BVS) must undergo significant deformation prior to implantation in a diameter-reduction process known as crimping which enables minimally invasive surgery. Understanding the behavior of vascular scaffolds in this step provides twofold benefits: first, it ensures the BVS is able to accommodate stresses occurring during this process to prevent failure, and further, it provides information on the radial strength of the BVS, a key metric to understanding its post-implant performance in the artery. To capitalize on the fast manufacturing speed AM provides, a low time cost solution for understanding scaffold performance during this step is necessary. Through simulation of the BVS crimping process in ABAQUS using experimentally obtained bulk material properties, we have developed a qualitative analysis tool which is capable of accurately comparing relative performance trends of varying BVS designs during crimping in a fraction of the time of experimental testing, thereby assisting in the integration of informed design into the additive manufacturing process.

3D-Printed Electroactive Hydrogel Architectures with Sub-100 µm Resolution Promote Myoblast Viability.

3D-printed hydrogel scaffolds functionalized with conductive polymers have demonstrated significant potential in regenerative applications for their structural tunability, physiochemical compatibility, and electroactivity. Controllably generating conductive hydrogels with fine features, however, has proven challenging. Here, micro-continuous liquid interface production (µCLIP) method is utilized to 3D print poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels. With a unique in-situ polymerization approach, a sulfonated monomer is first incorporated into the hydrogel matrix and subsequently polymerized into a conjugated polyelectrolyte, poly(4-(2,3-dihydro-thieno[3,4-b][1,4]dioxin-2-ylmethoxy)-butane-1 sulfonic acid sodium salt (PEDOT-S). Rod structures are fabricated at different crosslinking levels to investigate PEDOT-S incorporation and its effect on bulk hydrogel electronic and mechanical properties. After demonstrating that PEDOT-S does not significantly compromise the structures of the bulk material, pHEMA scaffolds are fabricated via µCLIP with features smaller than 100 µm. Scaffold characterization confirms PEDOT-S incorporation bolstered conductivity while lowering overall modulus. Finally, C2C12 myoblasts are seeded on PEDOT-pHEMA structures to verify cytocompatibility and the potential of this material in future regenerative applications. PEDOT-pHEMA scaffolds promote increased cell viability relative to their non-conductive counterparts and differentially influence cell organization. Taken together, this study presents a promising new approach for fabricating complex conductive hydrogel structures for regenerative applications.