Enhanced stem cell niche through microporous annealed particle scaffolds

Although stem cell therapy holds promises for intractable diseases, its efficacy has been limited by low retention and function of transplanted cells. Two of the key challenges for cell-based therapies are localization and cell function control once injected in a patient. Co-delivery of cells with hydrogels can mitigate these issues by localizing cells at a disease site and enhancing retention. However, the gold standard method, in situ gelation after injection with cells, confines transplanted cells and secreted therapeutic molecules within scaffolds due to the nanoporous nature of the hydrogel mesh. Confined cells are confounded from participating in regeneration, leading to poor outcomes. Moreover, it has been challenging to modulate the biophysical properties of such hydrogels independently from porosity for effective stem cell functional control.Here we show that microparticle scaffolds that can be co-injected locally with therapeutic cells and assembled in situ to generate a stem cell niche with interconnected microscale pore networks automatically formed in the void space between packed spherical particles. This approach enables enhanced migration and cell-cell connections between cells and transport of therapeutic molecules as well as higher cell proliferation in vitro and retention in vivo. Another key point is the modulation of biophysical properties independently from microporosity. Our scaffold provides a tunable porous environment by changing the physical properties of hydrogel building blocks. Using this platform technology, we demonstrated increased cell activity, such as proliferation and secretion, while the microporosity of the scaffolds induced tissue infiltration and vascularization. This approach achieves localized delivery of stem cells in a non-invasive manner creating a highly-tunable stem cell niche in situ which we envision can advance stem cell therapies as well as other cell-based therapies

Enhanced stem cell niche through microporous annealed particle scaffolds

Although stem cell therapy holds promises for intractable diseases, its efficacy has been limited by low retention and function of transplanted cells. Two of the key challenges for cell-based therapies are localization and cell function control once injected in a patient. Co-delivery of cells with hydrogels can mitigate these issues by localizing cells at a disease site and enhancing retention. However, the gold standard method, in situ gelation after injection with cells, confines transplanted cells and secreted therapeutic molecules within scaffolds due to the nanoporous nature of the hydrogel mesh. Confined cells are confounded from participating in regeneration, leading to poor outcomes. Moreover, it has been challenging to modulate the biophysical properties of such hydrogels independently from porosity for effective stem cell functional control.Here we show that microparticle scaffolds that can be co-injected locally with therapeutic cells and assembled in situ to generate a stem cell niche with interconnected microscale pore networks automatically formed in the void space between packed spherical particles. This approach enables enhanced migration and cell-cell connections between cells and transport of therapeutic molecules as well as higher cell proliferation in vitro and retention in vivo. Another key point is the modulation of biophysical properties independently from microporosity. Our scaffold provides a tunable porous environment by changing the physical properties of hydrogel building blocks. Using this platform technology, we demonstrated increased cell activity, such as proliferation and secretion, while the microporosity of the scaffolds induced tissue infiltration and vascularization. This approach achieves localized delivery of stem cells in a non-invasive manner creating a highly-tunable stem cell niche in situ which we envision can advance stem cell therapies as well as other cell-based therapies

Using a wireless touch screen tablet personal computer is feasible to assess the quality of Breast Cancer Survivorship

Background: Evidence supporting a tablet personal computer (PC)-based mode for a systemic approach to managing the breast cancer survival is limited. Objective: The objective of this study was to evaluate whether a tablet personal computer (PC) survey is feasible for screening the risks of the recurrence of breast cancer and the survivor issues associated with breast cancer treatment. Materials and methods: A descriptive study design was used. A pilot test of the tablet PC survey for its feasibility was undertaken using 40 breast cancer survivors at a university affiliated cancer management-survivorship clinic. The tablet PC survey was evaluated by structured questionnaires designed to assess patient experiences responding to the tablet PC-based surveys and user friendliness of the device itself. Results: Older patients and those with a lower education were more likely to have difficulty with the tablet PC administration and required assistance. Both physicians and nurses reported that the tablet PC survey was a useful tool that assisted healthcare professionals with providing quality of care. Conclusion: This pilot test supported the feasibility of a tablet PC survey as a vehicle for breast cancer survivorship management. Keywords: Breast cancer, Survivorship, Tablet, Surve

Cell Delivery: Enhanced In Vivo Delivery of Stem Cells using Microporous Annealed Particle Scaffolds (Small 39/2019)

Delivery to the proper tissue compartment is a major obstacle hampering the potential of cellular therapeutics for medical conditions. Delivery of cells within biomaterials may improve localization, but traditional and newer void-forming hydrogels must be made in advance with cells being added into the scaffold during the manufacturing process. Injectable, in situ cross-linking microporous scaffolds are recently developed that demonstrate a remarkable ability to provide a matrix for cellular proliferation and growth in vitro in three dimensions. The ability of these scaffolds to deliver cells in vivo is currently unknown. Herein, it is shown that mesenchymal stem cells (MSCs) can be co-injected locally with microparticle scaffolds assembled in situ immediately following injection. MSC delivery within a microporous scaffold enhances MSC retention subcutaneously when compared to cell delivery alone or delivery within traditional in situ cross-linked nanoporous hydrogels. After two weeks, endothelial cells forming blood vessels are recruited to the scaffold and cells retaining the MSC marker CD29 remain viable within the scaffold. These findings highlight the utility of this approach in achieving localized delivery of stem cells through an injectable porous matrix while limiting obstacles of introducing cells within the scaffold manufacturing process

Injectable Drug‐Releasing Microporous Annealed Particle Scaffolds for Treating Myocardial Infarction

Intramyocardial injection of hydrogels offers great potential for treating myocardial infarction (MI) in a minimally invasive manner. However, traditional bulk hydrogels generally lack microporous structures to support rapid tissue ingrowth and biochemical signals to prevent fibrotic remodeling toward heart failure. To address such challenges, a novel drug-releasing microporous annealed particle (drugMAP) system is developed by encapsulating hydrophobic drug-loaded nanoparticles into microgel building blocks via microfluidic manufacturing. By modulating nanoparticle hydrophilicity and pregel solution viscosity, drugMAP building blocks are generated with consistent and homogeneous encapsulation of nanoparticles. In addition, the complementary effects of forskolin (F) and Repsox (R) on the functional modulations of cardiomyocytes, fibroblasts, and endothelial cells in vitro are demonstrated. After that, both hydrophobic drugs (F and R) are loaded into drugMAP to generate FR/drugMAP for MI therapy in a rat model. The intramyocardial injection of MAP gel improves left ventricular functions, which are further enhanced by FR/drugMAP treatment with increased angiogenesis and reduced fibrosis and inflammatory response. This drugMAP platform represents a new generation of microgel particles for MI therapy and will have broad applications in regenerative medicine and disease therapy

Activating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healing.

Microporous annealed particle (MAP) scaffolds are flowable, in situ crosslinked, microporous scaffolds composed of microgel building blocks and were previously shown to accelerate wound healing. To promote more extensive tissue ingrowth before scaffold degradation, we aimed to slow MAP degradation by switching the chirality of the crosslinking peptides from L- to D-amino acids. Unexpectedly, despite showing the predicted slower enzymatic degradation in vitro, D-peptide crosslinked MAP hydrogel (D-MAP) hastened material degradation in vivo and imparted significant tissue regeneration to healed cutaneous wounds, including increased tensile strength and hair neogenesis. MAP scaffolds recruit IL-33 type 2 myeloid cells, which is amplified in the presence of D-peptides. Remarkably, D-MAP elicited significant antigen-specific immunity against the D-chiral peptides, and an intact adaptive immune system was required for the hydrogel-induced skin regeneration. These findings demonstrate that the generation of an adaptive immune response from a biomaterial is sufficient to induce cutaneous regenerative healing despite faster scaffold degradation

LIGHT (TNFSF14) enhances osteogenesis of human bone marrow-derived mesenchymal stem cells.

Osteoporosis is a progressive systemic skeletal disease associated with decreased bone mineral density and deterioration of bone quality, and it affects millions of people worldwide. Currently, it is treated mainly using antiresorptive and osteoanabolic agents. However, these drugs have severe adverse effects. Cell replacement therapy using mesenchymal stem cells (MSCs) could serve as a treatment strategy for osteoporosis in the future. LIGHT (HVEM-L, TNFSF14, or CD258) is a member of the tumor necrosis factor superfamily. However, the effect of recombinant LIGHT (rhLIGHT) on osteogenesis in human bone marrow-derived MSCs (hBM-MSCs) is unknown. Therefore, we monitored the effects of LIGHT on osteogenesis of hBM-MSCs. Lymphotoxin-β receptor (LTβR), which is a LIGHT receptor, was constitutively expressed on the surface of hBM-MSCs. After rhLIGHT treatment, calcium and phosphate deposition in hBM-MSCs, stained by Alizarin red and von Kossa, respectively, significantly increased. We performed quantitative real-time polymerase chain reaction to examine the expressions of osteoprogenitor markers (RUNX2/CBFA1 and collagen I alpha 1) and osteoblast markers (alkaline phosphatase, osterix/Sp7, and osteocalcin) and immunoblotting to assess the underlying biological mechanisms following rhLIGHT treatment. We found that rhLIGHT treatment enhanced von Kossa- and Alizarin red-positive hBM-MSCs and induced the expression of diverse differentiation markers of osteogenesis in a dose-dependent manner. WNT/β-catenin pathway activation strongly mediated rhLIGHT-induced osteogenesis of hBM-MSCs, accelerating the differentiation of hBM-MSCs into osteocytes. In conclusion, the interaction between LIGHT and LTβR enhances osteogenesis of hBM-MSCs. Therefore, LIGHT might play an important role in stem cell therapy