Stereolithography is a solid freeform technique (SFF) that was introduced in the late 1980s Although many other techniques have been developed since then, stereolithography remains one of the most powerful and versatile of all SFF techniques It has the highest fabrication accuracy and an increasing number of materials that can be processed is becoming available In this paper we discuss the characteristic features of the stereolithography technique and compare it to other SFF techniques The biomedical applications of stereolithography are reviewed, as well as the biodegradable resin materials that have been developed for use with stereolithography Finally, an overview of the application of stereolithography in preparing porous structures for tissue engineering is given

A review on stereolithography and its applications in biomedical engineering

Among various classes of biomaterials, the majority of non-centrosymmetric crystalline materials exhibit piezoelectric properties, i.e., the accumulation of charge in response to applied mechanical stress or deformation. Due to the growing interest in nanomaterials, piezoelectric nano-biomaterials have been widely investigated, leading to remarkable advancements throughout the last two decades. Piezoelectric properties, high surface energy, targeting properties, and intricate cell–material interactions render piezoelectric nanomaterials highly attractive for application in therapeutics as well as regenerative medicine. Herein, the major focus is to highlight the wide range of applications of piezoelectric nano-biomaterials in drug delivery, theranostics, and tissue regeneration. After a brief introduction to piezoelectricity, an overview is provided on the major classes of piezoelectric biomaterials as well as a description of the origin of biopiezoelectricity in different tissues and macromolecules. Subsequently, relevant properties and postfabrication strategies of nanostructured piezoelectric biomaterials are discussed aiming to maximize piezoresponse. Finally, recent studies on nanopiezoceramics and piezopolymers are presented, with specific focus on barium titanate, zinc oxide, and polyvinylidene fluoride.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/adfm.201909045

Piezoelectric Nano‐Biomaterials for Biomedicine and Tissue Regeneration

Electrospinning nanofiber scaffolds for soft and hard tissue regeneration

Milestones and current achievements in development of multifunctional bioscaffolds for medical application

Animal models of human disease.

Surgical treatment of tendon lesions still yields unsatisfactory clinical outcomes. The use of bioresorbable scaffolds represents a way forward to improve tissue repair. Scaffolds for tendon reconstruction should have a structure mimicking that of the natural tendon, while providing adequate mechanical strength and stiffness. In this paper, electrospun nanofibers of two crosslinked PLLA/Collagen blends (PLLA/Coll-75/25, PLLA/Coll-50/50) were developed and then wrapped in bundles, where the nanofibers are predominantly aligned along the bundles. Bundle morphology was assessed via SEM and high-resolution x-ray computed tomography (XCT). The 0.4-micron resolution in XCT demonstrated a biomimetic morphology of the bundles for all compositions, with a predominant nanofiber alignment and some scatter (50–60% were within 12° from the axis of the bundle), similar to the tendon microstructure. Human fibroblasts seeded on the bundles had increased metabolic activity from day 7 to day 21 of culture. The stiffness, strength and toughness of the bundles are comparable to tendon fascicles, both in the as-spun condition and after crosslinking, with moderate loss of mechanical properties after ageing in PBS (7 and 14 days). PLLA/Coll-75/25 has more desirable mechanical properties such as stiffness and ductility, compared to the PLLA/Coll-50/50. This study confirms the potential to bioengineer tendon fascicles with enhanced 3D structure and biomechanical properties.

/pdf/tendon-fascicle-inspired-nanofibrous-scaffold-of-polylactic-20ic1lo4um.pdf

Tendon fascicle-inspired nanofibrous scaffold of polylactic acid/collagen with enhanced 3D-structure and biomechanical properties

Lesions of tendons and ligaments account for over 40% of the musculoskeletal lesions. Surgical techniques and materials for repair and regeneration are currently not satisfactory. The high rate of post-operative complications and failures mainly relates to the technical difficulties in replicating the complex multiscale hierarchical structure and the mechanical properties of the native tendons and ligaments. With the aim of overcoming the limitations of non-biomimetic devices, we developed a hierarchical structure replicating the organization of tendons and ligaments. The scaffold consists of multiple bundles made of resorbable electrospun nanofibers of Poly-L-Lactic acid (PLLA) having tailored dimensions, wrapped in a sheath of nanofibers able to compact the construct. The bundles in turn consist of electrospun nanofibers with a preferential direction. High-resolution x-ray tomographic investigation at nanometer resolution confirmed that the morphology of the single bundles and of the entire scaffold replicated the hierarchical arrangement in the natural tendons and ligaments. To confirm that these structures could adequately restore tendons and ligaments, we measured the tensile stiffness, strength and toughness. The mechanical properties were in the range required to replace and repair tendons and ligaments. Furthermore, human fibroblasts were able to attach to the scaffolds and showed an increase in cell number, indicated by an increase in metabolic activity over time. Fibroblasts were preferentially aligned along the electrospun nanofibers. These encouraging in vitro results open the way for the next steps towards in vivo regeneration of tendons and ligaments.

/pdf/multiscale-hierarchical-bioresorbable-scaffolds-for-the-3665tpjtbi.pdf

Multiscale hierarchical bioresorbable scaffolds for the regeneration of tendons and ligaments.

Microfluidic-based tissue-on-a-chip devices have generated significant research interest for biomedical applications, such as pharmaceutical development, as they can be used for small volume, high throughput studies on the effects of therapeutics on tissue-mimics. Tissue-on-a-chip devices are evolving from basic 2D cell cultures incorporated into microfluidic devices to complex 3D approaches, with modern designs aimed at recapitulating the dynamic and mechanical environment of the native tissue. Thus far, most tissue-on-a-chip research has concentrated on organs involved with drug uptake, metabolism and removal (e.g., lung, skin, liver, and kidney); however, models of the drug metabolite target organs will be essential to provide information on therapeutic efficacy. Here, we develop an osteogenesis-on-a-chip device that comprises a 3D environment and fluid shear stresses, both important features of bone. This inexpensive, easy-to-fabricate system based on a polymerized High Internal Phase Emulsion (polyHIPE) supports proliferation, differentiation and extracellular matrix production of human embryonic stem cell-derived mesenchymal progenitor cells (hES-MPs) over extended time periods (up to 21 days). Cells respond positively to both chemical and mechanical stimulation of osteogenesis, with an intermittent flow profile containing rest periods strongly promoting differentiation and matrix formation in comparison to static and continuous flow. Flow and shear stresses were modeled using computational fluid dynamics. Primary cilia were detectable on cells within the device channels demonstrating that this mechanosensory organelle is present in the complex 3D culture environment. In summary, this device aids the development of ‘next-generation’ tools for investigating novel therapeutics for bone in comparison with standard laboratory and animal testing.

/pdf/design-and-evaluation-of-an-osteogenesis-on-a-chip-22ork3lwyg.pdf

Design and Evaluation of an Osteogenesis-on-a-Chip Microfluidic Device Incorporating 3D Cell Culture

Tendon injuries represent an unsolved clinical need. Electrospun bundles using blends of poly-L-lactic acid (PLLA) and collagen (Coll) in different percentages were prepared by an ‘ad hoc’ crosslinking system to increase the mechanical properties and reduce the loss of collagen after ageing in a physiological environment. The mechanical properties and cell proliferation were tested. High-resolution xray tomography was also performed to investigate the morphologyof the bundles. Keywords—Electrospinning, tendon tissue engineering, x-ray tomography, cell viability.

L. Boyle

Papers

Tendon fascicle-inspired nanofibrous scaffold of polylactic acid/collagen with enhanced 3D-structure and biomechanical properties

Multiscale hierarchical bioresorbable scaffolds for the regeneration of tendons and ligaments.

Design and Evaluation of an Osteogenesis-on-a-Chip Microfluidic Device Incorporating 3D Cell Culture

Fabrication and characterization of electrospun scaffolds for tendon reconstruction