In this open-label randomized clinical trial, HLA-identical sibling-matched hematopoietic stem cells (HSC) were transplanted (non-MSCs group, n ¼ 15) or cotransplanted with mesenchymal stem cells (MSCs) (MSCs group, n ¼ 10) in hematologic malignancy patients. The median number of MSCs infused was 3.4 Â 10 5 kg À1 (range, 0.3-15.3 Â 10 5 kg À1 ). MSCs infusions were well tolerated. The median time to neutrophil engraftment (absolute neutrophil count 40.5 Â 10 9 l À1 ) was 16 days for MSCs group and 15 days for non-MSCs group. The median time to platelet engraftment (platelet count 450 Â 10 9 l À1 ) was 30 and 27 days, respectively. Grades II-IV acute graft-versus-host disease (GVHD) was observed respectively, in one (11.1%) and eight (53.3%) evaluable patients. Chronic GVHD was found in one (14.3%) and four (28.6%) evaluable patients. The number of patients who relapsed were six (60.0%) and three (20.0%), and the 3-year disease-free survivals were 30.0 and 66.7%, respectively. Thus cotransplantation of MSCs and HSCs may prevent GVHD, but the relapse rate is obviously higher than the control group. We conclude that use of MSCs must be handled with extreme caution before a large-scale clinical trial is performed.

Conductive hydrogel scaffolds have important applications for electroactive tissue repairs. However, the development of conductive hydrogel scaffolds tends to incorporate nonbiodegradable conductive nanomaterials that will remain in the human body as foreign matters. Herein, a biodegradable conductive hybrid hydrogel is demonstrated based on the integration of black phosphorus (BP) nanosheets into the hydrogel matrix. To address the challenge of applying BP nanosheets in tissue engineering due to its intrinsic instability, a polydopamine (PDA) modification method is developed to improve the stability. Moreover, PDA modification also enhances interfacial bonding between pristine BP nanosheets and the hydrogel matrix. The incorporation of polydopamine-modified black phosphorous (BP@PDA) nanosheets into the gelatin methacryloyl (GelMA) hydrogels significantly enhances the electrical conductivity of the hydrogels and improves the cell migration of mesenchymal stem cells (MSCs) within the 3D scaffolds. On the basis of the gene expression and protein level assessments, the BP@PDAincorporated GelMA scaffold can significantly promote the differentiation of MSCs into neural-like cells under the synergistic electrical stimulation. This strategy of integrating biodegradable conductive BP nanomaterials within a biocompatible hydrogel provides a new insight into the design of biomaterials for broad applications in tissue engineering of electroactive tissues, such as neural, cardiac, and skeletal muscle tissues.

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An electroactive scaffold integrated with noninvasive in vivo electrical-stimulation (ES) capability shows great promise in the repair and regeneration of damaged tissues. Developing high-performance piezoelectric biomaterials which can simultaneously serve as both a biodegradable tissue scaffold and controllable electrical stimulator remains a great challenge. Herein, we constructed a biodegradable high-performance 3D piezoelectric scaffold with ultrasound (US)-driven wireless ES capability, and demonstrated its successful application for the repair of spinal cord injuries in a rat model. The 3D multichannel piezoelectric scaffold was prepared by electrospinning of poly­(lactic acid) (PLA) nanofibers incorporated with biodegradable high-performance piezoelectric potassium sodium niobate (K0.5Na0.5NbO3, KNN) nanowires. With programmed US irradiation as a remote mechanical stimulus, the on-demand in vivo ES with an adjustable timeline, duration, and strength can be delivered by the 3D piezoelectric scaffold. Under proper US excitation, the 3D tissue scaffolds made of the piezoelectric composite nanofibers can accelerate the recovery of motor functions and enhance the repair of spinal cord injury. The immunohistofluorescence investigation indicated that the 3D piezoelectric scaffolds combined with the US-driven in vivo ES promoted neural stem cell differentiation and endogenous angiogenesis in the lesion. This work highlights the potential application of a biodegradable high-performance piezoelectric scaffold providing US-driven on-demand electrical cues for regenerative medicine.

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