The focus in the field of biomedical engineering has shifted in recent years to biodegradable polymers and, in particular, polyesters. Dozens of polyester-based medical devices are commercially available, and every year more are introduced to the market. The mechanical performance and wide range of biodegradation properties of this class of polymers allow for high degrees of selectivity for targeted clinical applications. Recent research endeavors to expand the application of polymers have been driven by a need to target the general hydrophobic nature of polyesters and their limited cell motif sites. This review provides a comprehensive investigation into advanced strategies to modify polyesters and their clinical potential for future biomedical applications.

Biomedical Applications of Biodegradable Polyesters.

Advances and challenges in stem cell culture.

Polystyrene (PS) has brought in vitro cell culture from its humble beginnings to the modern era, propelling dozens of research fields along the way. This review discusses the development of the material, fabrication, and treatment approaches to create the culture material. However, native PS surfaces poorly facilitate cell adhesion and growth in vitro. To overcome this, liquid surface deposition, energetic plasma activation, and emerging functionalization methods transform the surface chemistry. This review seeks to highlight the many potential applications of the first widely accepted polymer growth surface. Although the majority of in vitro research occurs on two-dimensional surfaces, the importance of three-dimensional (3D) culture models cannot be overlooked. The methods to transition PS to specialized 3D culture surfaces are also reviewed. Specifically, casting, electrospinning, 3D printing, and microcarrier approaches to shift PS to a 3D culture surface are highlighted. The breadth of applications of the material makes it impossible to highlight every use, but the aim remains to demonstrate the versatility and potential as both a general and custom cell culture surface. The review concludes with emerging scaffolding approaches and, based on the findings, presents our insights on the future steps for PS as a tissue culture platform.

The Evolution of Polystyrene as a Cell Culture Material.

Stem cells hold great promise for widespread biomedical applications, for which stem cell fate needs to be well tailored. Besides biochemical cues, accumulating evidence has demonstrated that spatiotemporal biophysical cues (especially mechanical cues) imposed by cell microenvironments also critically impact on the stem cell fate. As such, various biomaterials, especially hydrogels due to their tunable physicochemical properties and advanced fabrication approaches, are developed to spatiotemporally manipulate biophysical cues in vitro so as to recapitulate the 3D mechanical microenvironment where stem cells reside in vivo. Here, the main mechanical cues that stem cells experience in their native microenvironment are summarized. Then, recent advances in the design of hydrogel materials with spatiotemporally tunable mechanical properties for engineering 3D the spatiotemporal mechanical microenvironment of stem cells are highlighted. These in vitro engineered spatiotemporal mechanical microenvironments are crucial for guiding stem cell fate and their potential biomedical applications are subsequently discussed. Finally, the challenges and future perspectives are presented.

3D Spatiotemporal Mechanical Microenvironment: A Hydrogel-Based Platform for Guiding Stem Cell Fate.

Many people, especially old and middle-aged, suffer from pain and disabilities caused by cartilage degradation. There are many surgical methods for cartilage treatment, however, none of the...

Alginate Based Scaffolds for Cartilage Tissue Engineering: A Review

Tissue engineering is an alternative method for articular cartilage repair. Mechanical stimulus has been found to be an important element to the healthy development of chondrocytes and maintenance of their native phenotype. To enhance nutrient transport and apply mechanical stress, we have developed a novel bioreactor, the tubular perfusion system (TPS), to culture chondrocytes in three-dimensional scaffolds. In our design, chondrocytes are encapsulated in alginate scaffolds and placed into a tubular growth chamber, which is perfused with media to enhance nutrient transfer and expose cells to fluid flow. Results demonstrate that TPS culture promotes the proliferation of chondrocytes compared to static culture as shown by DNA content and histochemical staining. After 14 days of culture, low messenger RNA expression of proinflammatory and apoptotic markers in TPS bioreactor culture confirmed that a flow rate of 3 mL/min does not damage the chondrocytes embedded in alginate scaffolds. Additionally, cells cultured in the TPS bioreactor showed increased gene expression levels of aggrecan, type II collagen, and superficial zone protein compared to the static group, indicative of the emergence of the superficial zone specific phenotype. Therefore, the TPS bioreactor is an effective means to enhance the proliferation and phenotype maintenance of chondrocytes in vitro.

Tubular perfusion system for chondrocyte culture and superficial zone protein expression.

Application of adipose-derived mesenchymal stromal cells (AMSCs)-derived extracellular vesicles (EVs) in skin wound healing has been documented. In this study, we investigated the therapeutic potential of AMSCs-derived EVs in skin wound healing through delivery of microRNA-10b (miR-10b). HaCaT cells were treated with H2O2 to establish the skin wound cell models. Next, the binding affinity between miR-194, PEA15, and CDK6 was identified. Additionally, EVs were isolated from the culture medium of AMSC sheets, followed by incubation with H2O2-treated HaCaT cells to detect cell proliferation, migration, and apoptosis using gain- or loss-of-function experiments. Lastly, the mice skin wound models were also established to assess skin wound healing ability. miR-10b was down-regulated in the skin trauma models and enriched in the EVs of AMSC sheets. Moreover, miR-10b derived from EVs targeted PEA15 to promote CDK6 expression, thereby stimulating the proliferation and migration of H2O2-damaged HaCaT cells but inhibiting apoptosis. In vivo experiments further ascertained the therapeutic functionality of AMSC sheets-derived EVs-miR-10b. In summary, AMSC sheets-derived EVs carrying miR-10b promoted CDK6 expression to intensify skin wound healing by regulating PEA15. 

Adipose mesenchymal stem cell sheets-derived extracellular vesicles-microRNA-10b promote skin wound healing by elevating expression of CDK6.

Pericardium-based cardiovascular devices are currently bound by a 10-year maximum lifetime due to detrimental calcification and degradation. The goal of this work is to develop a novel synthetic material to create a lasting replacement for malfunctioning or diseased tissue in the cardiovascular system. This study couples poly(propylene fumarate) (PPF) and a natural biomaterial together in an unprecedented hybrid composite and evaluates the composite versus the standard glutaraldehyde-treated tissue. The polymer reinforcement is hypothesized to provide initial physical protection from proteolytic enzymes and degradation, but leave the original collagen and elastin matrix unaltered. The calcification rate and durability of the hybrid material are evaluated in vitro and in an in vivo subdermal animal model. Results demonstrate that PPF is an effective support and leads to significantly less calcium deposition, important metrics when evaluating cardiovascular material. By avoiding chemical crosslinking of the tissue and associated side effects, PPF-reinforced pericardium as a biohybrid material offers a promising potential direction for further development in cardiovascular material alternatives. Eliminating the basis for the majority of cardiovascular prosthetic failures could revolutionize expectations for extent of cardiovascular repair.

/pdf/reinforced-pericardium-as-a-hybrid-material-for-2p0wfilols.pdf

Reinforced pericardium as a hybrid material for cardiovascular applications.

We have recently developed a bioreactor that can apply both shear and compressive forces to engineered tissues in dynamic culture. In our system, alginate hydrogel beads with encapsulated human mesenchymal stem cells (hMSCs) were cultured under different dynamic conditions while subjected to periodic, compressive force. A customized pressure sensor was developed to track the pressure fluctuations when shear forces and compressive forces were applied. Compared to static culture, dynamic culture can maintain a higher cell population throughout the study. With the application of only shear stress, qRT-PCR and immunohistochemistry revealed that hMSCs experienced less chondrogenic differentiation than the static group. The second study showed that chondrogenic differentiation was enhanced by additional mechanical compression. After 14 days, alcian blue staining showed more extracellular matrix formed in the compression group. The upregulation of the positive chondrogenic markers such as Sox 9, aggrecan, and type II collagen were demonstrated by qPCR. Our bioreactor provides a novel approach to apply mechanical forces to engineered cartilage. Results suggest that a combination of dynamic culture with proper mechanical stimulation may promote efficient progenitor cell expansion in vitro, thereby allowing the culture of clinically relevant articular chondrocytes for the treatment of articular cartilage defects.

Effect of Dynamic Culture and Periodic Compression on Human Mesenchymal Stem Cell Proliferation and Chondrogenesis

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Papers

Tubular perfusion system for chondrocyte culture and superficial zone protein expression.

Adipose mesenchymal stem cell sheets-derived extracellular vesicles-microRNA-10b promote skin wound healing by elevating expression of CDK6.

Reinforced pericardium as a hybrid material for cardiovascular applications.

Effect of Dynamic Culture and Periodic Compression on Human Mesenchymal Stem Cell Proliferation and Chondrogenesis