RESUMEN
Free-form printing offers a novel biofabrication approach to generate complex shapes by depositing hydrogel materials within a temporary supportive environment. However, printed hydrogels typically lack the requisite mechanical properties and functionality of the desired tissue, limiting application and, more importantly, safety and efficacy of the implant. The study authors have developed an innovative nanoclay-based bioink to print high shape fidelity functional constructs for potential skeletal application. Laponite® (LAP) nanoclay was combined with gellan gum (GG) to generate a printable hydrogel that was highly stable in vitro, displayed limited swelling ability compared with the silicate-free control and remained stable over time. An agarose fluid gel was found to provide the requisite support for the deposition of the material ink and preservation of the printed structure before crosslinking. Printed C2C12 myoblasts remained viable and displayed extensive proliferation over 21 days in culture. Cell-laden scaffolds demonstrated functionality within 1 day of culture in vitro and that was preserved over 3 weeks. Analysis of absorption and release mechanisms from LAP-GG using model proteins (lysozyme and bovine serum albumin) demonstrated the retention capability of the clay-based materials for compound localisation and absence of burst release. Vascular endothelial growth factor âwas loaded within the agarose fluid gel and absorbed by the material ink via absorption during deposition. The 3D-printed constructs were implanted on the chorioallantoic membrane of a 10-day-old developing chick. Extensive and preferential vasculature infiltration was observed in LAP-GG-loaded vascular endothelial growth factor constructs compared with controls (p<0.01 and p<0.0001) after only 7 days of incubation. The current studies demonstrate, for the first time, the application of innovative LAP-GG 3D constructs in the generation of growth factor-loaded 3D constructs for potential application in skeletal tissue repair.
RESUMEN
Recent advances in regenerative medicine have confirmed the potential to manufacture viable and effective tissue engineering 3D constructs comprising living cells for tissue repair and augmentation. Cell printing has shown promising potential in cell patterning in a number of studies enabling stem cells to be precisely deposited as a blueprint for tissue regeneration guidance. Such manufacturing techniques, however, face a number of challenges including; (i) post-printing cell damage, (ii) proliferation impairment and, (iii) poor or excessive final cell density deposition. The use of hydrogels offers one approach to address these issues given the ability to tune these biomaterials and subsequent application as vectors capable of delivering cell populations and as extrusion pastes. While stem cell-laden hydrogel 3D constructs have been widely established in vitro, clinical relevance, evidenced by in vivo long-term efficacy and clinical application, remains to be demonstrated. This review explores the central features of cell printing, cell-hydrogel properties and cell-biomaterial interactions together with the current advances and challenges in stem cell printing. A key focus is the translational hurdles to clinical application and how in vivo research can reshape and inform cell printing applications for an ageing population.
Asunto(s)
Bioimpresión/métodos , Huesos/fisiología , Tinta , Medicina Regenerativa , Células Madre/citología , Huesos/efectos de los fármacos , Humanos , Hidrogeles/farmacología , Células Madre/efectos de los fármacos , Ingeniería de TejidosRESUMEN
AIM: The aim of the present study was to implement and evaluate a system of care for patients with chronic leg ulceration (CLU) in Poland. METHODS: All patients within two defined geographical areas in Poland were identified for inclusion in the study. A model of care was developed based on guidelines, including the appropriate education of health professionals treating patients, access to non-invasive methods to determine the ulcer aetiology, compression therapy in those with proven venous ulceration. RESULTS: In total 309 patients were identified with CLU at the start of the study (120 men, 189 women). Both regions had a similar profile of patients having a median (IQR) duration of ulceration of 96 (30-168) months. Most (75.7%) patients were assessed using clinical signs and symptoms alone, with a mean (SD) number of treatments per week at 1.8 (1.9) visits. Two years after implementation, the numbers of patients had reduced to 205 (86 men, 119 women) a reduction of 33%. Post implementation more patients were treated at home (49.3% versus 19.5%) with a corresponding reduction in those seen at health centres (35.6% versus 63.3%). The mean (SD) number of visits was reduced to 1.3 (0.7). During implementation the healing rate at 30 weeks improved from 73.3% to 82.9%, with a corresponding reduction in amputations from 6.3% to 2.1%. While the cost per patient was higher post-implementation, the overall cost of treating patients within the service reduced from 3847 to 2913 per week. CONCLUSION: The development and implementation of an evidence based system of care for patients with CLU in Poland is both clinically and cost effective. This may be used as a model for other regions of Poland.