In recent decades, the biomedical applications of mesenchymal stem cells (MSCs) have attracted increasing attention. MSCs are easily extracted from the bone marrow, fat, and synovium, and differentiate into various cell lineages according to the requirements of specific biomedical applications. As MSCs do not express significant histocompatibility complexes and immune stimulating molecules, they are not detected by immune surveillance and do not lead to graft rejection after transplantation. These properties make them competent biomedical candidates, especially in tissue engineering. We present a brief overview of MSC extraction methods and subsequent potential for differentiation, and a comprehensive overview of their preclinical and clinical applications in regenerative medicine, and discuss future challenges.

Cartilage injuries are typically caused by trauma, chronic overload, and autoimmune diseases. Owing to the avascular structure and low metabolic activities of chondrocytes, cartilage generally does not self-repair following an injury. Currently, clinical interventions for cartilage injuries include chondrocyte implantation, microfracture, and osteochondral transplantation. However, rather than restoring cartilage integrity, these methods only postpone further cartilage deterioration. Stem cell therapies, especially mesenchymal stem cell (MSCs) therapies, were found to be a feasible strategy in the treatment of cartilage injuries. MSCs can easily be isolated from mesenchymal tissue and be differentiated into chondrocytes with the support of chondrogenic factors or scaffolds to repair damaged cartilage tissue. In this review, we highlighted the full success of cartilage repair using MSCs, or MSCs in combination with chondrogenic factors and scaffolds, and predicted their pros and cons for prospective translation to clinical practice.

The therapy of burns is a challenging clinical issue. Burns are long-term injuries, and numerous patients suffer from chronic pain. Burn treatment includes management, infection control, wound debridement and escharotomy, dressing coverage, skin transplantation, and the use of skin substitutes. The future of advanced care of burn wounds lies in the development of “active dressings”. Hydrogel dressings have been employed universally to accelerate wound healing based on their unique properties to overcome the limitations of existing treatment methods. This review briefly introduces the advantages of hydrogel dressings and discusses the development of new hydrogel dressings for wound healing along with skin regeneration. Further, the treatment strategies for burns, ranging from external to clinical, are reviewed, and the functional classifications of hydrogel dressings along with their clinical value for burns are discussed.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder implicated in multiple joint affection and even disability. The activated macrophages perform a predominant role in onset and persistence of RA. Scavenger receptor (SR), one of several receptors overexpressed on the activated macrophages, is a specific biomarker for targeted therapy of numerous chronic inflammation diseases like RA. In this work, dextran sulfate-graft-methotrexate conjugate (DS-g-MTX) is synthesized and characterized, which exhibits excellent targetability to SR on the activated RAW 264.7 cells. Additionally, the enhanced accumulation and potent inflammatory inhibition are observed in the affected joint after intravenous injection of DS-g-MTX, compared to the treatment with dextran-graft-methotrexate (Dex-g-MTX), as is confirmed by the detection of histopathology and pro-inflammatory cytokines. Our work highlights DS-g-MTX as a potential therapeutic option for RA aiming the SR-expressed activated macrophages.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, leading to articular synovial hyperplasia, cartilage destruction, and bone erosion. In RA pathophysiology, the activated macrophages contribute to the initiation and maintenance of the disease. Folate receptor, an overexpressed receptor on the activated macrophages, becomes a promising target site for RA treatment. In this work, the folate-modified dextran–methotrexate conjugate (noted as Dex-g-MTX/FA) was synthesized with an untargeted dextran–methotrexate prodrug (referred as Dex-g-MTX) as the control. The two prodrugs self-assembled into spherical micelles with both scales of about 90 nm and exhibited sustained MTX release. Dex-g-MTX/FA exhibited more superior cellular uptake mediated by the folate receptor and higher cytotoxicity toward macrophages activated by lipopolysaccharide (LPS) compared with Dex-g-MTX. Moreover, Dex-g-MTX/FA possessed improved biodistribution at the lesion site and stronger remission of RA through the inhibition of proinflammatory cytokines in comparison with both Dex-g-MTX and free MTX. These results demonstrated that the folate-targeted prodrug, i.e., Dex-g-MTX/FA, is a potential strategy for activated macrophage-targeted therapy of RA.