Chronic wounds develop when the orderly process of cutaneous wound healing is delayed or disrupted. Development of a chronic wound is associated with significant morbidity and financial burden to the individual and health-care system. Therefore, new therapeutic modalities are needed to address this serious condition. Mesenchymal stem cells (MSCs) promote skin repair, but their clinical use has been limited due to technical challenges. Extracellular vesicles (EVs) are particles released by cells that carry bioactive molecules (lipids, proteins, and nucleic acids) and regulate intercellular communication. EVs (exosomes, microvesicles, and apoptotic bodies) mediate key therapeutic effects of MSCs. In this review we examine the experimental data establishing a role for EVs in wound healing. Then, we explore techniques for designing EVs to function as a targeted drug delivery system and how EVs can be incorporated into biomaterials to produce a personalized wound dressing. Finally, we discuss the status of clinically deploying EVs as a therapeutic agent in wound care.
Congenital tracheomalacia and tracheal stenosis are commonly seen in premature infants. In adulthood, are typically related with chronic obstructive pulmonary disease, and can occur secondarily from tracheostomy, prolong intubation, trauma, infection and tumors. Both conditions are life-threatening when not managed properly. There are still some surgical limitations for certain pathologies, however tissue engineering is a promising approach to treat massive airway dysfunctions. 3D-bioprinting have contributed to current preclinical and clinical efforts in airway reconstruction. Several strategies have been used to overcome the difficulty of airway reconstruction such as scaffold materials, construct designs, cellular types, biologic components, hydrogels and animal models used in tracheal reconstruction. Nevertheless, additional long-term in vivo studies need to be performed to assess the efficacy and safety of tissue-engineered tracheal grafts in terms of mechanical properties, behavior and, the possibility of further stenosis development.
To establish whether a novel biomaterial scaffold with tunable degradation profile will aid in cartilage repair of chondral defects versus microfracture alone in vitro and in a rat model in vivo. In vitro—Short- and long-term degradation scaffolds were seeded with culture expanded articular chondrocytes or bone marrow mesenchymal stem cells. Cell growth and differentiation were evaluated with cell morphological studies and gene expression studies. In vivo—A microfracture rat model was used in this study to evaluate the repair of cartilage and subchondral bone with the contralateral knee serving as the empty control. The treatment groups include (1) empty osteochondral defect, (2) polycaprolactone copolymer–based polyester polyurethane–urea (PSPU-U) caffold short-term degradative profile, and (3) PSPU-U scaffold long-term degradative profile. After placement of the scaffold, the rats were then allowed unrestricted activity as tolerated, and histological analyses were performed at 4, 8, and 16 weeks. The cartilage defect was measured and compared with the contralateral control side. In vitro—Long-term scaffolds showed statistically significant higher levels of aggrecan and type II collagen expression compared with short-term scaffolds. In vivo—Within 16 weeks postimplantation, there was new subchondral bone formation in both scaffolds. Short-term scaffolds had a statistically significant increase in defect filling and better qualitative histologic fill compared to control. The PSPU short-term degradation scaffold may aid in cartilage repair by ultimately incorporating the scaffold into the microfracture procedure.
Mesenchymal stem cell (MSC)-based exosomes have garnered attention as a viable therapeutic for post-traumatic cartilage injury and osteoarthritis of the knee; however, efforts for application have been limited due to issues with variable dosing and rapid clearance in vivo. Scaffolds laden with MSC-based exosomes have recently been investigated as a solution to these issues. Here, we review in vivo studies and highlight key strengths and potential clinical uses of exosome–scaffold therapeutics for treatment of post-traumatic cartilage injury and osteoarthritis. In vivo animal studies were gathered using keywords related to the topic, revealing 466 studies after removal of duplicate papers. Inclusion and exclusion criteria were applied for abstract screening and full-text review. Thirteen relevant studies were identified for analysis and extraction. Three predominant scaffold subtypes were identified: hydrogels, acellular extracellular matrices, and hyaluronic acid. Each scaffold–exosome design showcased unique properties with relation to gross findings, tissue histology, biomechanics, and gene expression. All designs demonstrated a reduction in inflammation and induction of tissue regeneration. The results of our review show that current exosome–scaffold therapeutics demonstrate the capability to halt and even reverse the course of post-traumatic cartilage injury and osteoarthritis. While this treatment modality shows incredible promise, future research should aim to characterize long-term biocompatibility and optimize scaffold designs for human treatment.
» Three-dimensional (3D)-printing technology has evolved dramatically in the last 30 years, from large machines with poor resolution to those with micron-level capabilities that sit on a desktop. This technology is being utilized in numerous medical applications, particularly in orthopaedic surgery. » Over the past decade, technological advances have allowed for the application of this technology to the field of tissue engineering through the process of 3D bioprinting. » Of interest to orthopaedic surgeons, active areas of research utilizing this technology involve the bioprinting of articular cartilage, bone, menisci, and intervertebral discs.