Preclinical assessment of IL-1ß primed human umbilical cord mesenchymal stem cells for tendon functional repair through TGF-ß/IL-10 signaling.

Background: Inadequate repair capacity and disturbed immune compartments are the main pathological causes of tendinopathy. Transplantation of mesenchymal stem cells (MSCs) become an effective clinic option to alleviate tendinopathy. Interleukin-1ß (IL-1ß) could confer on MSCs enhanced immunoregulatory capability to remodel the repair microenvironment favoring tissue repair. Therefore, IL-1ß activated UC-MSCs (1ßUC-MSCs) may exert favorable efficacy in promoting tendon repair in a preclinical tendinopathy rat model. Methods: Tendon-derived stem cells (TDSCs) were isolated and characterized. In vitro, the levels of immunoregulatory-related cytokines such as IL-1ß, IL-6, IL-10, and TGF-ß secreted by 1ßUC-MSCs and unprimed UC-MSCs was measured. And tendon-specific markers expressed by TDSCs cultured with primed cultured medium (CM) or unprimed CM were detected. In vivo, Achilles tendinopathy was induced by 30 µL collagenase I injection in Sprague Dawley rats. One week later, the rats were randomly injected with UC-MSCs primed with IL-1ß (106 cells per tendon), UC-MSCs, or PBS. After rats were sacrificed, histological evaluation, electron microscopy, biomechanical tests, gait performance were conducted to evaluate the structural and functional recovery of Achilles tendons. The inflammation and metabolic state of the extracellular matrix, and the potential mechanism were assessed by immunohistochemical staining and Western blot. Results: UC-MSCs were activated by IL-1ß to secrete higher levels of IL-10 and TGF-ß while the secretion levels of IL-6 and IL-1ß were not changed significantly, promoting a higher expression level of COL I and TNMD in TDSCs under proinflammatory environment. In vivo, the transplanted 1ßUC-MSCs could survive up to 5 weeks after injection with tenogenic differentiation and improved tendon healing histologically semi-quantified by modified Bonar scores. This structural regeneration was further confirmed by observation of ultrastructural morphology, and led to good functional recovery including improved biomechanical properties and gait performance. During this process, the inflammatory response and metabolism of the extracellular matrix was improved through TGF-ß/IL-10 pathway. Conclusion: This study demonstrated that the transplantation of UC-MSCs activated by IL-1ß exhibited satisfactory ability for promoting tendon functional repair in a tendinopathy rat model. During this process, the balance of inflammatory response and extracellular matrix metabolism was remodeled, and the TGF-ß/Smad2/3 and IL-10 signaling pathways were activated simultaneously. We cautiously conclude that the IL-1ß primed UC-MSCs could be a promising strategy for enhancing the ability of MSCs to treat tendinopathy.

Preclinical assessment on neuronal regeneration in the injury-related microenvironment of graphene-based scaffolds.

As the application of graphene nanomaterials gets increasingly attractive in the field of tissue engineering and regenerative medicine, the long-term evaluation is necessary and urgent as to their biocompatibility and regenerative capacity in different tissue injuries, such as nerve, bone, and heart. However, it still remains controversial about the potential biological effects of graphene on neuronal activity, especially after severe nerve injuries. In this study, we establish a lengthy peripheral nerve defect rat model and investigate the potential toxicity of layered graphene-loaded polycaprolactone scaffold after implantation during 18 months in vivo. In addition, we further identify possible biologically regenerative effects of this scaffold on myelination, axonal outgrowth, and locomotor function recovery. It is confirmed that graphene-based nanomaterials exert negligible toxicity and repair large nerve defects by dual regulation of Schwann cells and astroglia in the central and peripheral nervous systems. The findings enlighten the future of graphene nanomaterial as a key type of biomaterials for clinical translation in neuronal regeneration.

Clinical assessment of calcium phosphate cement to treat tibial plateau fractures.

The aim of this study was to examine histological changes in bone morphology after surgical treatment of tibial plateau fractures using calcium phosphate cement as a substitute for autologous bone grafting. A total of 42 patients with tibial plateau fractures were treated with open reduction, internal fixation, and calcium phosphate cement. A further 34 control patients underwent open reduction and internal fixation. Bone samples for histology were obtained during the surgery. Bone healing and functional recovery were assessed. Bone cell counts were significantly higher in samples obtained during the second surgery (81.2) compared with the first surgery (45.4, p < 0.001). Bone healing scores significantly increased with time after surgery (p < 0.001). Mean Hospital for Special Surgery knee scores were rated "good" for both the calcium phosphate cement group (82.3) and control group (79.4) in 12 months, and were not significantly different between groups. Histological examination of samples obtained during the second surgery revealed well-arranged trabeculae, in addition to new bone and blood vessel formation. These histological, radiological, and functional findings suggest that calcium phosphate cement may be an effective substitute for autologous bone grafting to treat tibial plateau fractures.

Incidence, management, and prognosis of early ulnar nerve dysfunction in type C fractures of distal humerus.

BACKGROUND: Displaced comminuted of the distal humerus in adults are among the most complex fractures to be managed effectively. The ulnar nerve is at high risk of impingement secondary to injury, operation, and postoperative rehabilitation in these fractures. In this study we focus on the incidence, management, and prognosis of early ulnar nerve dysfunction in the course of treating type C fractures of distal humerus. METHODS: We examine a patient sample of 117 consecutive AO type C fractures of distal humerus, between June 1998 and October 2005. Twenty-nine patients exhibited preoperative ulnar nerve compression symptoms (incidence 24.8%) and were divided into two groups randomly, which received treatment of anterior subfascial transposition or in situ decompression of the ulnar nerve respectively, in conjunction with internal fixation with medial and lateral plates. RESULTS: The subgroup of 88 patients without preoperative ulnar nerve symptoms remained asymptomatic postoperatively (0% incidence of late ulnar nerve dysfunction). According to Bishop rating system, excellent and good results of ulnar nerve function were achieved in 13 of 15 patients (86.7%) in the transposition group, 8 of 14 patients (57.1%) in the in situ decompression group. The results difference is statistically significant (p < 0.05). CONCLUSIONS: We conclude that neurolysis and anterior subfascial transposition of vascularized ulnar nerve during open reduction and internal fixation of type C fractures of the distal humerus is beneficial in cases of early ulnat nerve dysfunction.