The clinical use of human bone marrow–derived mesenchymal stem cells (BM-MSCs) has been hampered by their poor performance after transplantation into failing hearts. Here, to improve the therapeutic potential of BM-MSCs, we developed a strategy termed in vivo priming in which BM-MSCs are primed in vivo in myocardial infarction (MI)–induced hearts through genetically engineered hepatocyte growth factor–expressing MSCs (HGF-eMSCs) that are encapsulated within an epicardially implanted 3D cardiac patch. Primed BM-MSCs through HGF-eMSCs exhibited improved vasculogenic potential and cell viability, which ultimately enhanced vascular regeneration and restored cardiac function to the MI hearts. Histological analyses further demonstrated that the primed BM-MSCs survived longer within a cardiac patch and conferred cardioprotection evidenced by substantially higher numbers of viable cardiomyocytes in the MI hearts. These results provide compelling evidence that this in vivo priming strategy can be an effective means to enhance the cardiac repair of MI hearts.

Background: Chronic full-thickness rotator cuff tears (FTRCTs) represent a major clinical concern because they show highly compromised healing capacity. Purpose: To evaluate the efficacy of using a 3-dimensional (3D) bioprinted scaffold with human umbilical cord blood (hUCB)–mesenchymal stem cells (MSCs) for regeneration of chronic FTRCTs in a rabbit model. Study Design: Controlled laboratory study. Methods: A total of 32 rabbits were randomly assigned to 4 treatment groups (n = 8 per group) at 6 weeks after a 5-mm FTRCT was created on the supraspinatus tendon. Group 1 (G1-SAL) was transplanted with normal saline. Group 2 (G2-MSC) was transplanted with hUCB-MSCs (0.2 mL, 1 × 106) into FTRCTs. Group 3 (G3-3D) was transplanted with a 3D bioprinted construct without MSCs, and group 4 (G4-3D+MSC) was transplanted with a 3D bioprinted construct containing hUCB-MSCs (0.2 mL, 1 × 106 cells) into FTRCTs. All 32 rabbits were euthanized at 4 weeks after treatment. Examination of gross morphologic changes and histologic results was performed on all rabbits after sacrifice. Motion analysis was also performed before and after treatment. Results: In G4-3D+MSC, newly regenerated collagen type 1 fibers, walking distance, fast walking time, and mean walking speed were greater than those in G2-MSC based on histochemical and motion analyses. In addition, when compared with G3-3D, G4-3D+MSC showed more prominent regenerated tendon fibers and better parameters of motion analysis. However, there was no significant difference in gross tear size among G2-MSC, G3-3D, and G4-3D+MSC, although these groups showed significant decreases in tear size as compared with the control group (G1-SAL). Conclusion: Findings of this study show that a tissue engineering strategy based on a 3D bioprinted scaffold filled with hUCB-MSCs can improve the microenvironment for regenerative processes of FTRCT without any surgical repair. Clinical Relevance: In the case of rotator cuff tear, the cell loss of the external MSCs can be increased by exposure to synovial fluid. Therefore, a 3D bioprinted scaffold in combination with MSCs without surgical repair may be effective in increasing cell retention in FTRCT.

As a class of representative intractable diseases, cardiovascular disease (CVD) is the most common cause of global mortality, accounting for approximately 17.9 million deaths each year. At the end of the disease stage, surgery for replacement of cardiovascular (CV) tissue is inevitably required due to the limited regeneration capacity of CV tissue. However, the currently available methods (e.g. autografts, allografts, xenografts, prostheses) have limited therapeutic efficacy because of donor shortage, immunological transplant rejection, anticoagulant therapy, and less durability. To overcome these limitations, CV tissue engineering technology has been extensively explored to develop replaceable tissue and organs for in vivo transplantation. In addition, 3D tissue models are also studied for in vitro mechanistic study and therapeutic screening. To accomplish this, there has been tremendous progress in studying various CV tissue-specific biomaterials and advanced 3D bioprinting techniques to enhance the physiological and anatomical relevance of engineered CV tissues. Moreover, a variety of evaluation methods have been investigated to validate the unique structural properties and electrical activity of the engineered CV tissues towards non- or less-invasive and real-time assessments in 3D volumetric structures. In this review, we systemically present and discuss the advantages and applications of CV tissue-specific biomaterials, 3D bioprinting techniques, and assessment methods that can facilitate real-time monitoring. A thorough understanding of advanced strategies in CV tissue engineering can be utilized to guide work on next-generation therapeutics for CVD.

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