Journal of Tissue Engineering and Regenerative Medicine最新文献

Myocardial infarction, stroke, and pulmonary embolism are all deadly conditions associated with excessive thrombus formation. Standard treatment for these conditions involves systemic delivery of thrombolytic agents to break up clots and restore blood flow; however, this treatment can impact the hemostatic balance in other parts of the vasculature, which can lead to excessive bleeding. To avoid this potential danger, targeted thrombolytic treatments that can successfully target thrombi and release an effective therapeutic load are necessary. Because activated platelets and fibrin make up a large proportion of clots, these two components provide ample opportunities for targeting. This review will highlight potential thrombus targeting mechanisms as well as recent advances in thrombolytic therapies which utilize blood-cells and clotting proteins to effectively target and lyse clots.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease of unknown cause. The interaction of immune system cells and the secretion of inflammatory cytokines with synovial cells leads to severe inflammation in the affected joints. Currently, medications, including non-steroidal anti-inflammatory drugs, glucocorticoids, and more recently, disease-modifying anti-rheumatic drugs, are used to reduce inflammation. However, long-term use of these drugs causes adverse effects or resistance in a considerable number of RA patients. Recent findings revealed the safety and efficacy of mesenchymal stromal cells (MSCs)-based therapies both in RA animal models and clinical trials. Here, the beneficial effects of bone marrow-derived heterogeneous MSCs (BM-hMSCs) and Wharton jelly-derived MSCs (WJ-MSCs) at early passages were compared to BM-derived clonal MSCs (BM-cMSCs) at high passage number on a rat model of collagen-induced arthritis. Results showed that systemic delivery of MSCs significantly reversed adverse changes in body weight, paw swelling, and arthritis score in all MSC-treated groups. Radiological images and histological evaluation demonstrated the therapeutic effects of MSCs. There was a decrease in serum level of anti-collagen type II immunoglobulin G and the inflammatory cytokines interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor-α in all MSC-treated groups. In contrast, an increase in inhibitory cytokines transforming growth factor-β and IL-10 was seen. Notably, the long-term passages of BM-cMSCs could alleviate RA symptoms similar to the early passages of WJ-MSCs and BM-hMSCs. The importance of BM-cMSCs is the potential to establish cell banks with billions of cells derived from a single donor that could be a competitive cell-based therapy to treat RA.

The use of membrane barriers and bone grafting materials in endodontic surgery promotes healing by regeneration rather than repair by scar tissue. Due to its valuable regenerative and therapeutic properties, the human amniotic membrane can support ideal periapical rehabilitation and promote better healing after surgery. The current trial aimed to evaluate the amniotic membrane's healing potential and compare it with platelet-rich fibrin using color doppler sonography. The current study is a randomized, double-blinded, parallel-group, single-center study. Thirty-four systematically healthy individuals requiring endodontic surgery who fulfilled all inclusion and exclusion criteria were selected and randomly placed in two groups. Surgical curettage of the bony lesion was performed and filled with hydroxyapatite graft. Amniotic membrane (Group 1) and platelet-rich fibrin (Group 2) were placed over the bony crypt, and the flap was sutured back. The lesion's surface area and vascularity were the parameters assessed with ultrasound and color doppler. and observations: The groups found a significant difference in mean vascularity at 1 month and mean vascularity change from baseline to 1 month (p < 0.05). Mean surface area had no statistically significant difference between the groups. However, in terms of the percentage change in surface area, a significant difference was found from baseline to 6 months (p < 0.05). Amniotic membrane was a significantly better promoter of angiogenesis than platelet-rich fibrin in the current trial. The osteogenic potential of both materials was similar. However, the clinical application, availability, and cost-effectiveness of amniotic membrane support it as a promising therapeutic alternative in clinical translation. Further large-scale trials and histologic studies are warranted.

This review paper is motivated by a Back-to-Basics presentation given by the author at the 2022 Orthopaedic Research Society meeting in Tampa, Florida. I was tasked with providing a brief history of research leading up to the introduction of functional tissue engineering (FTE) for tendon and ligament repair. Beginning in the 1970s, this timeline focused on two common orthopedic soft tissue problems, anterior cruciate ligament ruptures in the knee and supraspinatus tendon injuries in the shoulder. Historic changes in the field over the next 5 decades revealed a transformation from a focus more on mechanics (called “bioMECHANICS”) on a larger (tissue) scale to a more recent focus on biology (called “mechanoBIOLOGY”) on a smaller (cellular and molecular) scale. Early studies by surgeons and engineers revealed the importance of testing conditions for ligaments and tendons (e.g., high strain rates while avoiding subject disuse and immobility) and the need to measure in vivo forces in these tissues. But any true tissue engineering and regeneration in these early decades was limited more to the use of auto-, allo- and xenografts than actual generation of stimulated cell-scaffold constructs in culture. It was only after the discovery of tissue engineering in 1988 and the recognition of frequent rotator cuff injuries in the early 1990s, that biologists joined surgeons and engineers to discover mechanical and biological testing criteria for FTE. This review emphasizes the need for broader and more inclusive collaborations by surgeons, biologists and engineers in the short term with involvement of those in biomaterials, manufacturing, and regulation of new products in the longer term.

Autografting, a major treatment for bone fractures, has potential risks related to the required surgery and disease transmission. Bone morphogenetic proteins (BMPs) are the most common osteogenic factors used for bone-healing applications. However, BMP delivery can have shortcomings such as a short half-life and the high cost of manufacturing the recombinant proteins. Gene delivery methods have demonstrated promising alternative strategies for producing BMPs or other osteogenic factors using engineered cells. These approaches can also enable temporal overexpression and local production of the therapeutic genes in the target tissues. This review addresses recent progress on engineered viral, non-viral, and RNA-mediated gene delivery systems that are being used for bone repair and regeneration. Advances in clustered regularly interspaced short palindromic repeats/Cas9 genome engineering for bone tissue regeneration also is discussed.