The complex management of severe burn victims requires an integrative collaboration of multidisciplinary specialists in order to ensure quality and excellence in healthcare. This multidisciplinary care has quickly led to the integration of cell therapies in clinical care of burn patients. Specific advances in cellular therapy together with medical care have allowed for rapid treatment, shorter residence in hospitals and intensive care units, shorter durations of mechanical ventilation, lower complications and surgery interventions, and decreasing mortality rates. However, naturally fluctuating patient admission rates increase pressure towards optimized resource utilization. Besides, European translational developments of cellular therapies currently face potentially jeopardizing challenges on the policy front. The aim of the present work is to provide key considerations in burn care with focus on architectural and organizational aspects of burn centers, management of cellular therapy products, and guidelines in evolving restrictive regulations relative to standardized cell therapies. Thus, based on our experience, we present herein integrated management of risks and costs for preserving and optimizing clinical care and cellular therapies for patients in dire need.

We report the cases of 2 patients admitted to our hospital at a 17-year interval, both with 90% total body surface area (TBSA) burns. These two young patients were in good health before their accident, but major differences in time of intensive care and hospitalization were observed: 162 versus 76 days in intensive care unit and 18 versus 9.5 months for hospitalization, respectively. We have analyzed the different parameters side-by-side during their medical care and we have identified that the overall improved outcomes are mainly due to a better adapted fluid reanimation in combination with the evolution of the surgical management to encompass allogenic cellular therapy (Biological Bandages). Indeed, autologous cell therapy using keratinocytes has been used for over 30 years in our hospital with the same technical specifications; however, we have integrated the Biological Bandages and routinely used them for burn patients to replace cadaver skin since the past 15 years. Thus, patient 1 versus patient 2 had, respectively, 83% versus 80% TBSA for autologous cells, and 0% versus 189% for allogenic cells. Notably, it was possible that patient 2 was able to recover ∼6% TBSA with the use of Biological Bandages, by stimulating intermediate burn zones toward a spontaneous healing without requiring further skin grafting (on abdomen and thighs). The body zones where Biological Bandages were not applied, such as the buttocks, progressed to deeper-stage burns. Despite inherent differences to patients at their admission and the complexity of severe burn care, the results of these two case reports suggest that integration of innovative allogenic cell therapies in the surgical care of burn patients could have major implications in the final outcome.

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Hand tendon/ligament structural ruptures (tears, lacerations) often require surgical reconstruction and grafting, for the restauration of finger mechanical functions. Clinical-grade human primary progenitor tenocytes (FE002 cryopreserved progenitor cell source) have been previously proposed for diversified therapeutic uses within allogeneic tissue engineering and regenerative medicine applications. The aim of this study was to establish bioengineering and surgical proofs-of-concept for an artificial graft (Neoligaments Infinity-Lock 3 device) bearing cultured and viable FE002 primary progenitor tenocytes. Technical optimization and in vitro validation work showed that the combined preparations could be rapidly obtained (dynamic cell seeding of 105 cells/cm of scaffold, 7 days of co-culture). The studied standardized transplants presented homogeneous cellular colonization in vitro (cellular alignment/coating along the scaffold fibers) and other critical functional attributes (tendon extracellular matrix component such as collagen I and aggrecan synthesis/deposition along the scaffold fibers). Notably, major safety- and functionality-related parameters/attributes of the FE002 cells/finished combination products were compiled and set forth (telomerase activity, adhesion and biological coating potentials). A two-part human cadaveric study enabled to establish clinical protocols for hand ligament cell-assisted surgery (ligamento-suspension plasty after trapeziectomy, thumb metacarpo-phalangeal ulnar collateral ligamentoplasty). Importantly, the aggregated experimental results clearly confirmed that functional and clinically usable allogeneic cell-scaffold combination products could be rapidly and robustly prepared for bio-enhanced hand ligament reconstruction. Major advantages of the considered bioengineered graft were discussed in light of existing clinical protocols based on autologous tenocyte transplantation. Overall, this study established proofs-of-concept for the translational development of a functional tissue engineering protocol in allogeneic musculoskeletal regenerative medicine, in view of a pilot clinical trial.