Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors.

Adoptive cell therapy (ACT) has proven to be highly effective in treating blood cancers, but traditional approaches to ACT are poorly effective in treating solid tumors observed clinically. Novel delivery methods for therapeutic cells have shown promise for treatment of solid tumors when compared with standard intravenous administration methods, but the few reported approaches leverage biomaterials that are complex to manufacture and have primarily demonstrated applicability following tumor resection or in immune-privileged tissues. Here, we engineer simple-to-implement injectable hydrogels for the controlled co-delivery of CAR-T cells and stimulatory cytokines that improve treatment of solid tumors. The unique architecture of this material simultaneously inhibits passive diffusion of entrapped cytokines and permits active motility of entrapped cells to enable long-term retention, viability, and activation of CAR-T cells. The generation of a transient inflammatory niche following administration affords sustained exposure of CAR-T cells, induces a tumor-reactive CAR-T phenotype, and improves efficacy of treatment.

Effects of Mesenchymal Stem Cell-Derived Paracrine Signals and Their Delivery Strategies.

Mesenchymal stem cells (MSCs) have been widely studied as a versatile cell source for tissue regeneration and remodeling due to their potent bioactivity, which includes modulation of inflammation response, macrophage polarization toward proregenerative lineage, promotion of angiogenesis, and reduction in fibrosis. This review focuses on profiling the effects of paracrine signals of MSCs, commonly referred to as the secretome, and highlighting the various engineering approaches to tune the MSC secretome. Recent advances in biomaterials-based therapeutic strategies for delivery of MSCs and MSC-derived secretome in the form of extracellular vesicles are discussed, along with their advantages and challenges.

An Evaluation of Sensing Technologies to Measure Intraoperative Leg Length for Total Hip Arthroplasty.

Total hip arthroplasty (THA) procedures have been identified as high-volume procedures with growing prevalence. During the procedure, orthopedic surgeons largely rely solely on qualitative assessment to ensure an excessive limb length discrepancy (LLD) is not introduced from the implant selection. LLD can result in back pain and gait complications, with some cases of LLD requiring a revision procedure to mitigate. To address this issue, we evaluated several methods of sensing distance intraoperatively to determine the best approach to measure leg length during the THA procedure. A testing setup using a sawbones model of hip anatomy in the decubitus position was used as a simulation of the THA procedure to test the accuracy of each of the sensing modalities.

Nanofiber-hydrogel composite-mediated angiogenesis for soft tissue reconstruction.

Soft tissue losses from tumor removal, trauma, aging, and congenital malformation affect millions of people each year. Existing options for soft tissue restoration have several drawbacks: Surgical options such as the use of autologous tissue flaps lead to donor site defects, prosthetic implants are prone to foreign body response leading to fibrosis, and fat grafting and dermal fillers are limited to small-volume defects and only provide transient volume restoration. In addition, large-volume fat grafting and other tissue-engineering attempts are hampered by poor vascular ingrowth. Currently, there are no off-the-shelf materials that can fill the volume lost in soft tissue defects while promoting early angiogenesis. Here, we report a nanofiber-hydrogel composite that addresses these issues. By incorporating interfacial bonding between electrospun poly(ε-caprolactone) fibers and a hyaluronic acid hydrogel network, we generated a composite that mimics the microarchitecture and mechanical properties of soft tissue extracellular matrix. Upon subcutaneous injection in a rat model, this composite permitted infiltration of host macrophages and conditioned them into the pro-regenerative phenotype. By secreting pro-angiogenic cytokines and growth factors, these polarized macrophages enabled gradual remodeling and replacement of the composite with vascularized soft tissue. Such host cell infiltration and angiogenesis were also observed in a rabbit model for repairing a soft tissue defect filled with the composite. This injectable nanofiber-hydrogel composite augments native tissue regenerative responses, thus enabling durable soft tissue restoration outcomes.