The Biomedical Use of Silk: Past, Present, Future

Humans have long appreciated silk for its lustrous appeal and remarkable physical properties, yet as the mysteries of silk are unraveled, it becomes clear that this outstanding biopolymer is more than a high-tech fiber. This progress report provides a critical but detailed insight into the biomedical use of silk. This journey begins with a historical perspective of silk and its uses, including the long-standing desire to reverse engineer silk. Selected silk structure–function relationships are then examined to appreciate past and current silk challenges. From this, biocompatibility and biodegradation are reviewed with a specific focus of silk performance in humans. The current clinical uses of silk (e.g., sutures, surgical meshes, and fabrics) are discussed, as well as clinical trials (e.g., wound healing, tissue engineering) and emerging biomedical applications of silk across selected formats, such as silk solution, films, scaffolds, electrospun materials, hydrogels, and particles. The journey finishes with a look at the roadmap of next-generation recombinant silks, especially the development pipeline of this new industry for clinical use

Reverse-engineered silk hydrogels for cell and drug delivery

Silk is an important biopolymer for (bio)medical applications because of its unique and highly versatile structure and its robust clinical track record in human medicine. Silk can be processed into many material formats, including physically and chemically cross-linked hydrogels that have almost limitless applications ranging from tissue engineering to biomedical imaging and sensing. This concise review provides a detailed background of silk hydrogels, including silk structure–function relationships, biocompatibility and biodegradation, and it explores recent developments in silk hydrogel utilization, with specific reference to drug and cell delivery. We address common pitfalls and misconceptions while identifying emerging opportunities, including 3D printing

Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

As populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the US, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases, they are often associated with serious side effects including the development of oesophageal cancer, ocular inflammation, severe musculoskeletal pain, and osteonecrosis of the jaw. The use of autologous mesenchymal stromal cells/mesenchymal stem cells (MSCs) is a possible alternative therapeutic approach to tackle osteoporosis while overcoming the limitations of traditional treatment options. However, osteoporosis can cause a decrease in the numbers of MSCs, induce their senescence, and lower their osteogenic differentiation potential. Three-dimensional (3D) cell culture is an emerging technology that allows a more physiological expansion and differentiation of stem cells compared to cultivation on conventional flat systems. This review will discuss current understanding of the effects of different 3D cell culture systems on proliferation, viability, osteogenic differentiation, as well as on the immunomodulatory and anti-inflammatory potential of MSCs

The use of 3D printed microporous-strut polycaprolactone scaffolds for targeted local delivery of chemotherapeutic agent for breast cancer application

Local recurrent cancer remains a challenge for breast cancer patients receiving implants after mastectomy or lumpectomy. The use of radiotherapy and/or systemic administration of chemotherapeutic agents post-surgery can be beneficial yet they also kill healthy cells and introduce systemic side effects. In this study, a new method was introduced to utilize 3D printed microporous polycaprolactone (PCL) scaffolds as a multifunctional device—an implant and a drug delivery vehicle for targeted local delivery. Their microporous structure was characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The dependence of release profiles of Doxorubicin (DOX) loaded scaffolds on pH and ionic strength of the environment was demonstrated. Lastly, their chemotherapeutic effect was characterized by in vitro. Overall, the results demonstrated the utility of the microporosity and surface charge of PCL scaffolds to immobilize DOX for local, targeted drug delivery

Methylomic and phenotypic analysis of the ModH5 phasevarion of Helicobacter pylori

The Helicobacter pylori phase variable gene modH, typified by gene HP1522 in strain 26695, encodes a N6-adenosine type III DNA methyltransferase. Our previous studies identified multiple strain-specific modH variants (modH1 – modH19) and showed that phase variation of modH5 in H. pylori P12 influenced expression of motility-associated genes and outer membrane protein gene hopG. However, the ModH5 DNA recognition motif and the mechanism by which ModH5 controls gene expression were unknown. Here, using comparative single molecule real-time sequencing, we identify the DNA site methylated by ModH5 as 5′-Gm6ACC-3′. This motif is vastly underrepresented in H. pylori genomes, but overrepresented in a number of virulence genes, including motility-associated genes, and outer membrane protein genes. Motility and the number of flagella of H. pylori P12 wild-type were significantly higher than that of isogenic modH5 OFF or ΔmodH5 mutants, indicating that phase variable switching of modH5 expression plays a role in regulating H. pylori motility phenotypes. Using the flagellin A (flaA) gene as a model, we show that ModH5 modulates flaA promoter activity in a GACC methylation-dependent manner. These findings provide novel insights into the role of ModH5 in gene regulation and how it mediates epigenetic regulation of H. pylori motility.Full Tex