Umbilical Cord-Derived Wharton's Jelly for Regenerative Medicine Applications: A Systematic Review.

Musculoskeletal ailments affect millions of people around the world and place a high burden on healthcare. Traditional treatment modalities are limited and do not address underlying pathologies. Mesenchymal stem cells (MSCs) have emerged as an exciting therapeutic alternative and Wharton's jelly-derived mesenchymal stem cells (WJSCs) are some of these. This review reports the clinical and functional outcomes of the applications of WJSCs in orthopedic surgery. A systematic review was conducted utilizing the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The studies that used culture-expanded, mesenchymal stem or stromal cells, MSCs and/or connective tissues procured from Wharton's jelly (WJ), from January 2010 to October 2021, were included. Conventional non-operative therapies and placebos were used as comparisons. Six studies that directly discussed WJSCs use in an animal model or the basic scientific testing using an injury model were identified. Five publications studied cartilage injury, three studied degenerative disc disease, one was related to osteoarthritis, and one was related to osteochondral defects. The results of these studies suggested the benefits of WJSCs in the management of these orthopedic pathologies. To adequately assess the safety and efficacy of WJSCs in orthopedic surgery, further randomized controlled clinical studies are necessary.

Tibia Stress Fracture and Subsequent Nonunion Associated With High Morbidity Following Vascularized Fibula Graft Harvest.

There is little in the literature about tibial stress fracture after partial fibulectomy. As fibula strut grafting and vascularized fibula flap grafting becomes more common in the field of reconstructive surgery, the incidence of this complication will likely rise. The authors present the case of a 54-year-old woman with tibial stress fracture and subsequent nonunion following vascularized fibula graft harvest. The aim of this case report is to present a unique tibial stress fracture and nonunion following vascularized fibula flap for mandibular reconstruction and a discussion of the orthopedic management of this uncommon injury. The authors' goal is to educate both surgeons and patients about the altered biomechanics and subsequent risks associated with fibula strut graft harvest, from an orthopedic surgery perspective. By increasing physician awareness and obtaining better informed consent preoperatively, better health care outcomes associated with fibular graft harvesting can be obtained. [Orthopedics. 2021;44(2):e306-e308.].

Umbilical cord-derived Wharton's jelly for regenerative medicine applications in orthopedic surgery: a systematic review protocol.

BACKGROUND: Musculoskeletal injuries and conditions affect millions of individuals. These ailments are typically managed by immobilization, physiotherapy, or activity modification. Regenerative medicine has experienced tremendous growth in the past decades, especially in musculoskeletal medicine. Umbilical cord-derived Wharton's jelly is an exciting new option for such therapies. Wharton's jelly is a connective tissue located within the umbilical cord largely composed of mesenchymal stem cells and extracellular matrix components, including collagen, chondroitin sulfate, hyaluronic acid, and sulfated proteoglycans. Wharton's jelly is a promising and applicable biologic source for orthopedic regenerative application. METHODS: A systematic search will be conducted in PubMed, ScienceDirect, and Google Scholar databases of English, Italian, French, Spanish, and Portuguese language articles published to date. References will be screened and assessed for eligibility by two independent reviewers as per PRISMA guidelines. Articles will be considered without exclusion to sex, activity, or age. Studies will be included if they used culture-expanded, mesenchymal stem/stromal cells of mesenchymal stem cells and/or connective tissue obtained from Wharton's jelly. Studies will be excluded if Wharton's jelly is not the sole experimental examined cell type. Placebos, conventional non-operative therapies including steroid injections, exercise, and NSAIDs will be compared. The study selection process will be performed independently by two reviewers using a reference software. Data synthesis and meta-analysis will be performed separately for clinical and pre-clinical studies. DISCUSSION: The results will be published in relevant peer-reviewed scientific journals. Investigators will present results at national or international conferences. TRIAL REGISTRATION: The protocol was registered on PROSPERO international prospective register of systematic reviews prior to commencement, CRD42020182487 .

Bone graft substitutes for spine fusion: A brief review.

Bone graft substitutes are widely used in the field of orthopedics and are extensively used to promote vertebral fusion. Fusion is the most common technique in spine surgery and is used to treat morbidities and relieve discomfort. Allograft and autograft bone substitutes are currently the most commonly used bone grafts to promote fusion. These approaches pose limitations and present complications to the patient. Numerous alternative bone graft substitutes are on the market or have been developed and proposed for application. These options have attempted to promote spine fusion by enhancing osteogenic properties. In this review, we reviewed biology of spine fusion and the current advances in biomedical materials and biological strategies for application in surgical spine fusion. Our findings illustrate that, while many bone graft substitutes perform well as bone graft extenders, only osteoinductive proteins (recombinant bone morphogenetic proteins-2 and osteogenic protein-1) provide evidence for use as both bone enhancers and bone substitutes for specific types of spinal fusion. Tissue engineered hydrogels, synthetic polymer composites and viral based gene therapy also holds the potential to be used for spine fusion in future, though warrants further investigation to be used in clinical practice.

Surgical retrieval, isolation and in vitro expansion of human anterior cruciate ligament-derived cells for tissue engineering applications.

Injury to the ACL is a commonly encountered problem in active individuals. Even partial tears of this intra-articular knee ligament lead to biomechanical deficiencies that impair function and stability. Current options for the treatment of partial ACL tears range from nonoperative, conservative management to multiple surgical options, such as: thermal modification, single-bundle repair, complete reconstruction, and reconstruction of the damaged portion of the native ligament. Few studies, if any, have demonstrated any single method for management to be consistently superior, and in many cases patients continue to demonstrate persistent instability and other comorbidities. The goal of this study is to identify a potential cell source for utilization in the development of a tissue engineered patch that could be implemented in the repair of a partially torn ACL. A novel protocol was developed for the expansion of cells derived from patients undergoing ACL reconstruction. To isolate the cells, minced hACL tissue obtained during ACL reconstruction was digested in a Collagenase solution. Expansion was performed using DMEM/F12 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin (P/S). The cells were then stored at -80 ºC or in liquid nitrogen in a freezing medium consisting of DMSO, FBS and the expansion medium. After thawing, the hACL derived cells were then seeded onto a tissue engineered scaffold, PLAGA (Poly lactic-co-glycolic acid) and control Tissue culture polystyrene (TCPS). After 7 days, SEM was performed to compare cellular adhesion to the PLAGA versus the control TCPS. Cellular morphology was evaluated using immunofluorescence staining. SEM (Scanning Electron Microscope) micrographs demonstrated that cells grew and adhered on both PLAGA and TCPS surfaces and were confluent over the entire surfaces by day 7. Immunofluorescence staining showed normal, non-stressed morphological patterns on both surfaces. This technique is promising for applications in ACL regeneration and reconstruction.

In vitro evaluation of three-dimensional single-walled carbon nanotube composites for bone tissue engineering.

The purpose of this study was to develop three-dimensional single-walled carbon nanotube composites (SWCNT/PLAGA) using 10-mg single-walled carbon nanotubes (SWCNT) for bone regeneration and to determine the mechanical strength of the composites, and to evaluate the interaction of MC3T3-E1 cells via cell adhesion, growth, survival, proliferation, and gene expression. PLAGA (polylactic-co-glycolic acid) and SWCNT/PLAGA microspheres and composites were fabricated, characterized, and mechanical testing was performed. MC3T3-E1 cells were seeded and cell adhesion/morphology, growth/survival, proliferation, and gene expression analysis were performed to evaluate biocompatibility. Imaging studies demonstrated microspheres with uniform shape and smooth surfaces, and uniform incorporation of SWCNT into PLAGA matrix. The microspheres bonded in a random packing manner while maintaining spacing, thus resembling trabeculae of cancellous bone. Addition of SWCNT led to greater compressive modulus and ultimate compressive strength. Imaging studies revealed that MC3T3-E1 cells adhered, grew/survived, and exhibited normal, nonstressed morphology on the composites. SWCNT/PLAGA composites exhibited higher cell proliferation rate and gene expression compared with PLAGA. These results demonstrate the potential of SWCNT/PLAGA composites for musculoskeletal regeneration, for bone tissue engineering, and are promising for orthopedic applications as they possess the combined effect of increased mechanical strength, cell proliferation, and gene expression.