Effects of Therapy with Fibrin Glue combined with Mesenchymal Stem Cells (MSCs) on Bone Regeneration: A Systematic Review
Cell therapy strategies using mesenchymal stem cells (MSCs) carried in fibrin glue have shown promising results in regenerative medicine. MSCs are crucial for tissue healing because they have angiogenic, anti-apoptotic and immunomodulatory properties, in addition to the ability to differentiate into several specialized cell lines. Fibrin sealant or fibrin glue is a natural polymer involved in the coagulation process. Fibrin glue provides a temporary structure that favors angiogenesis, extracellular matrix deposition and cell-matrix interactions. Additionally, fibrin glue maintains the local and paracrine functions of MSCs, providing tissue regeneration through less invasive clinical procedures. Thus, the objective of this systematic review was to assess the potential of fibrin glue combined with MSCs in bone or cartilage regeneration. The bibliographic search was performed in the PubMed/MEDLINE, LILACS and Embase databases, using the descriptors ("fibrin sealant" OR "fibrin glue") AND "stem cells" AND "bone regeneration", considering articles published until 2021. In this case, 12 preclinical and five clinical studies were selected to compose this review, according to the eligibility criteria. In preclinical studies, fibrin glue loaded with MSCs, alone or associated with bone substitute, significantly favored bone defects regeneration compared to scaffold without cells. Similarly, fibrin glue loaded with MSCs presented considerable potential to regenerate joint cartilage injuries and multiple bone fractures, with significant improvement in clinical parameters and absence of postoperative complications. Therefore, there is clear evidence in the literature that fibrin glue loaded with MSCs, alone or combined with bone substitute, is a promising strategy for treating lesions in bone or cartilaginous tissue.
A novel autologous bone graft substitute comprised of rhBMP6 blood coagulum as carrier tested in a randomized and controlled Phase I trial in patients with distal radial fractures
Bone morphogenetic proteins (BMPs) are known to induce new bone formation in vivo but treating trabecular bone defects with a BMP based therapeutic remains controversial. Here, we evaluated the safety and efficacy of a novel Autologous Bone Graft Substitute (ABGS) comprised of recombinant human BMP6 (rhBMP6) dispersed within an autologous blood coagulum (ABC) as a physiological natural carrier in patients with a closed distal radial fracture (DRF). We enrolled 32 patients in a randomized, standard of care (SoC) and placebo (PBO) controlled, double-blinded Phase I First in Human (FiH) clinical trial. ABGS was prepared from peripheral blood as 250 μg rhBMP6/mL ABC or PBO (1 mL ABC containing excipients only) and was administered dorsally via a syringe injection into the fracture site following closed fracture fixation with 3 Kirschner wires. Patients carried an immobilization for 5 weeks and were followed-up for 0 to 26 weeks by clinical examination, safety, serial radiographic analyses and CT. During the 13 weeks follow-up and at 26 weeks post study there were no serious adverse reactions recorded. The results showed that there were no detectable anti-rhBMP6 antibodies in the blood of any of the 32 patients at 13- and 26-weeks following treatment. Pharmacokinetic analyses of plasma from patients treated with ABGS showed no detectable rhBMP6 at any time point within the first 24 hours following administration. The CT image and radiographic analyses score from patients treated with AGBS showed significantly accelerated bone healing as compared to PBO and SoC at 5 and 9 weeks (with high effect sizes and P=0.027), while at week 13 all patients had similar healing outcomes. In conclusion, we show that intraosseous administration of ABGS (250 μg rhBMP6/mL ABC) into the distal radial fracture site demonstrated a good tolerability with no serious adverse reactions as well as early accelerated trabecular bone healing as compared to control PBO and SoC patients.
The Safety of Blood Flow Restriction Training as a Therapeutic Intervention for Patients With Musculoskeletal Disorders: A Systematic Review
The American journal of sports medicine. 2019;:363546519882652
BACKGROUND The effectiveness of blood flow restriction training (BFRT) as compared with other forms of training, such as resistance training, has been evaluated in the literature in clinical and nonclinical populations. However, the safety of this intervention has been summarized only in healthy populations and not in clinical populations with musculoskeletal disorders. PURPOSE To evaluate the safety and adverse events associated with BFRT in patients with musculoskeletal disorders. STUDY DESIGN Systematic review. METHODS A literature search was conducted with 3 online databases (MEDLINE, CINAHL, and Embase). Eligibility criteria for selecting studies were as follows: (1) BFRT was used as a clinical intervention, (2) study participants had a disorder of the musculoskeletal system, (3) authors addressed adverse events, (4) studies were published in English, and (5) the intervention was performed with human participants. RESULTS Nineteen studies met eligibility criteria, with a pooled sample size of 322. Diagnoses included various knee-related disorders, inclusion body myositis, polymyositis or dermatomyositis, thoracic outlet syndrome, Achilles tendon rupture, and bony fractures. Nine studies reported no adverse events, while 3 reported rare adverse events, including an upper extremity deep vein thrombosis and rhabdomyolysis. Three case studies reported common adverse events, including acute muscle pain and acute muscle fatigue. In the randomized controlled trials, individuals exposed to BFRT were not more likely to have an adverse event than individuals exposed to exercise alone. Of the 19 studies, the adverse events were as follows: overall, 14 of 322; rare overall, 3 of 322; rare BFRT, 3 of 168; rare control, 0 of 154; any adverse BFRT, 10 of 168; any adverse control, 4 of 154. A majority of studies were excluded because they did not address safety. CONCLUSION BFRT appears to be a safe strengthening approach for knee-related musculoskeletal disorders, but further research is needed to make definitive conclusions and to evaluate the safety in other musculoskeletal conditions. Improved definitions of adverse events related to BFRT are needed to include clear criteria for differentiating among common, uncommon, and rare adverse events. Finally, further research is needed to effectively screen who might be at risk for rare adverse events.