Stem cell therapy for reconstruction of alveolar cleft and trauma defects in adults: A randomized controlled, clinical trial

BackgroundStem cell therapy with bone marrow‐derived mesenchymal stem cells is a promising tissue engineering strategy to promote regeneration of craniofacial bone.PurposeTo determine whether cell therapy with ex vivo expanded stem cell populations would be safe and efficacious in the regeneration of large alveolar defects in patients with a history of cleft palate or craniofacial trauma.Materials and MethodsEighteen patients (10 patients with traumatic injury and 8 patients with cleft palate) presenting with missing teeth associated with horizontal alveolar bone deficiencies were included in this randomized controlled clinical trial. Patients were randomized to receive either conventional autogenous block grafts or stem cell therapy. After a healing period of 4 months the treated sites were re‐entered and the bone width re‐assessed prior to implant placement. Implant stability was evaluated through torque testing of the implant upon insertion and at 6 months postloading.ResultsThe mean gain in bone width was 1.5 ± 1.5 mm in the stem cell therapy group and 3.3 ± 1.4 mm in the control group. Overall, bone gain was higher in trauma patients as compared to patients with cleft palate, for both the control and the stem cell therapy groups. Most postoperative complications were wound dehiscences and incision line openings. Implants were placed successfully in 5 out of 10 patients in the stem cell therapy group and in all 8 patients in the control group. One implant from the control/cleft palate group failed before loading, while the rest of the implants were loaded successfully and remained stable at 6 months. The patients who did not receive implants were re‐treated with autogenous block bone graft.ConclusionThe ability of stem cells to treat large alveolar defects is safe, yet, their ability to completely reconstitute large alveolar defects is limited. This approach requires further optimization to meet the outcomes seen using current methods to treat large defects, particularly those resultant of cleft palate.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138871/1/cid12506.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138871/2/cid12506_am.pd

Tension-Compression Loading with Chemical Stimulation Results in Additive Increases to Functional Properties of Anatomic Meniscal Constructs

Objective: This study aimed to improve the functional properties of anatomically-shaped meniscus constructs through simultaneous tension and compression mechanical stimulation in conjunction with chemical stimulation. Methods: Scaffoldless meniscal constructs were subjected to simultaneous tension and compressive stimulation and chemical stimulation. The temporal aspect of mechanical loadingwas studied by employing two separate five day stimulation periods. Chemical stimulation consisted of the application of a catabolic GAG-depleting enzyme, chondroitinase ABC (C-ABC), and an anabolic growth factor, TGF-b1. Mechanical and chemical stimulation combinations were studied through a full-factorial experimental design and assessed for histological, biochemical, and biomechanical properties following 4 wks of culture. Results: Mechanical loading applied from days 10–14 resulted in significant increases in compressive, tensile, and biochemical properties of meniscal constructs. When mechanical and chemical stimuliwere combined significant additive increases in collagen per wet weight (4-fold), compressive instantaneous (3-fold) and relaxation (2-fold) moduli, and tensile moduli in the circumferential (4-fold) and radial (6-fold) directions were obtained. Conclusions: This study demonstrates that a stimulation regimen of simultaneous tension and compression mechanical stimulation, C-ABC, and TGF-b1 is able to create anatomic meniscus constructs replicating the compressive mechanica

Dynamic Loading Of Anatomically Shaped Meniscal Constructs Generated Via Mri And micro-Ct Imaging

Several studies have established that dynamic stimulation by mixing media and dynamic compression enhances the production of extracellular matrix (ECM) and mechanical properties of tissue-engineered (TE) constructs seeded with articular chondrocytes. Very few studies have attempted to engineer a whole meniscus and none have attempted to dynamically stimulate this tissue in vitro. The overall objective of this dissertation was to investigate the effect of dynamic stimulation on the biochemical and mechanical properties of image-guided tissue engineered menisci. The central hypothesis of this dissertation is that mechanical stimulation will alter the ECM assembly and mechanical behavior of anatomically shaped constructs. The first specific aim developed a method of generating patient specific anatomically shaped menisci using an image guided approach and tested the feasibility of culturing these engineered constructs using bovine meniscal fibrochondrocytes. The second specific aim developed a method of quantitatively comparing the shape fidelity of anatomically shaped tissue engineered menisci using various imaging and fabrication techniques. The third specific aim tested the hypothesis that controlled media mixing will enhance tissue formation and mechanical properties of anatomically shaped constructs compared to static controls. The fourth specific aim tested the hypothesis that dynamic compressive loading would improve biochemical and mechanical properties of image-guided tissue engineered menisci. This work represents the first study to dynamically load an anatomically shaped engineered meniscus in vitro. The studies presented in this dissertation are the first attempts to examine the effects of mechanical stimulation on large volume anatomically shaped TE menisci. The findings presented highlight 1) the effectiveness of image-guided fabrication techniques in generating patient specific TE implants and 2) the potential mechanical stimulation has to enhance tissue growth in engineered constructs