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Abstract Over the past years, the development of innovative smart wound dressings is revolutionizing wound care management and research. Specifically, in the treatment of diabetic foot wounds, three-dimensional (3D) bioprinted patches may enable personalized medicine therapies. In the present work, a methacrylated hyaluronic acid (MeHA) bioink is employed to manufacture 3D printed patches to deliver small extracellular vesicles (sEVs) obtained from human mesenchymal stem cells (MSC-sEVs). The production of sEVs is maximized culturing MSCs in bioreactor. A series of in vitro analyses are carried out to demonstrate the influence of MSC-sEVs on functions of dermal fibroblasts and endothelial cells, which are the primary functional cells in skin repair process. Results demonstrate that both cell populations are able to internalize MSC-sEVs and that the exposure to sEVs stimulates proliferation and migration. In vivo experiments in a well-established diabetic mouse model of pressure ulcer confirm the regenerative properties of MSC-sEVs. The MeHA patch enhances the effectiveness of sEVs by enabling controlled release of MSC-sEVs over 7 days, which improve wound epithelialization, angiogenesis and innervation. The overall findings highlight that MSC-sEVs loading in 3D printed biomaterials represents a powerful technique, which can improve the translational potential of parental stem cell in terms of regulatory and economic impact.

Awareness of the potential for an ulcer to become a Marjolin’s ulcer is important for chronic wound management. Here we describe four cases of chronic ulcers progressing to malignant transformation with four completely different scenario and injury pattern. First case was a 41 years old male who presented with 24 years old complete traumatic paraplegia with ulcer as fungating mass at outer inferior quadrant of left gluteal region. The second case was a 15 year old traumatic knee injury with open wound which resulted in insensate foot and chronic osteomyelitis with recurrent ulcer with transformation to malignant ulcer. Third case is again 12 years old recurrent wound due to crush injury and osteomyelitis in the involved lower limb and last 57 years old case is different from the others, developed chronic wound from a minor cut without any specific precipitating factor which finally resulted in to marjolin’s ulcer. All the cases highlight the progression of chronic ulcer in to marjolin’s ulcer which is a very rare but deadly complication of recurrent or non-healing type of ulcers.