Posterolateral spinal fusion with autologous bone graft is considered the “gold standard” for lumbar degenerative disc disease (DDD) when surgical treatment is indicated. The potential role of mesenchymal stromal cells (MSCs) to replace the bone graft in this setting has not been fully addressed. To analyze the safety, feasibility and potential clinical efficacy of the implantation of autologous MSCs embedded with tricalcium phosphate as a therapeutic alternative to bone graft in patients with DDD during posterolateral spine fusion. Phase I/II single-arm prospective clinical trial. Eleven patients with monosegmental DDD at L4–L5 or L5–S1 level were included. Autologous bone marrow-derived MSC were expanded in our Good Manufacturing Practice (GMP) Facility and implanted during spinal surgery embedded in a tricalcium phosphate carrier. Monitoring of patients included a postoperative period of 12 months with four visits (after the 1st, 3rd, 6th, and 12th month), with clinical and radiological assessment that included the visual analog scale (VAS), the Oswestry disability index (ODI), the Short-Form Health Survey (SF-36), the vertebral fusion grade observed through a simple Rx, and the evaluation of possible complications or adverse reactions. In addition, all patients were further followed up to 5 years for outcome. Median age of patients included was 44 years (range 30–58 years), and male/female ratio was (6/5) L4–L5 and L5–S1 DDD was present five and six patients, respectively. Autologous MSCs were expanded in all cases. There were no adverse effects related to cell implantation. Regarding efficacy, both VAS and ODI scores improved after surgery. Radiologically, 80% of patients achieved lumbar fusion at the end of the follow-up. No adverse effects related to the procedure were recorded. The use of autologous MSCs for spine fusion in patients with monosegmental degenerative disc disease is feasible, safe, and potentially effective. no. EudraCT: 2010–018335-17 ; code Identifier: NCT01513694 ( clinicaltrials.gov ).

In the last few years, great interest has been focused on tissue engineering as a potential therapeutic approach for musculoskeletal diseases. The role of metallic implants for spinal fusion has been tested in preclinical and clinical settings. Titanium and tantalum have excellent biocompatibility and mechanical properties and are being used in this situation. On the other hand, the therapeutic role of mesenchymal stem cells (MSC) is extensively explored for their multilineage differentiation into osteoblasts. In vitro comparision of titanium and tantalum as MSCs scaffolds. In the present study, we have compared the in vitro expansion capacity, viability, immunophenotype (both explored by flow cytometry) and multi-differentiation ability of MSC cultured in the presence of either titanium or tantalum fragments. The adherence of MSC to either metal was demonstrated by electron microscopy. Both metals were able to carry MSC when transferred to new culture flasks. In addition, our study shows that culture of MSC with titanium or tantalum improves cell viability and maintains all their biological properties, with no significant differences regarding the metal employed. This would support the use of these combinations for clinical purposes, especially in the spinal fusion and reconstruction setting.

Introduction: Mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and multilineage differentiation. Their multipotential capacity and immunomodulatory properties have led to an increasing interest in their biological properties and therapeutic applications. Currently, the definition of MSCs relies on a combination of phenotypic, morphological and functional characteristics which are typically evaluated upon in vitro expansion, a process that may ultimately lead to modulation of the immunophenotypic, functional and/or genetic features of these cells. Therefore, at present there is great interest in providing markers and phenotypes for direct in vivo and ex vivo identification and isolation of MSCs.Methods: Multiparameter flow cytometry immunophenotypic studies were performed on 65 bone marrow (BM) samples for characterization of CD13^highCD105⁺CD45^–cells. Isolation and expansion of these cells was performed in a subset of samples in parallel to the expansion of MSCs from mononuclear cells following currently established procedures. The protein expression profile of these cells was further assessed on (paired) primary and in vitro expanded BM MSCs, and their adipogenic, chondrogenic and osteogenic differentiation potential was also determined.Results: Our results show that the CD13^highCD105⁺CD45⁻immunophenotype defines a minor subset of cells that are systematically present ex vivo in normal/reactive BM (n = 65) and that display immunophenotypic features, plastic adherence ability, and osteogenic, adipogenic and chondrogenic differentiation capacities fully compatible with those of MSCs. In addition, we also show that in vitro expansion of these cells modulates their immunophenotypic characteristics, including changes in the expression of markers currently used for the definition of MSCs, such as CD105, CD146 and HLA-DR.Conclusions: BM MSCs can be identified ex vivo in normal/reactive BM, based on a robust CD13^highCD105⁺and CD45⁻immunophenotypic profile. Furthermore, in vitro expansion of these cells is associated with significant changes in the immunophenotypic profile of MSCs.

Clinicians should be aware of the main methods and materials to face the challenge of bone shortage by manufacturing customized grafts, in order to repair defects. This study aims to carry out a bibliographic review of the existing methods to manufacture customized bone scaffolds through 3D technology and to identify their current situation based on the published papers. A literature search was carried out using “3D scaffold”, “bone regeneration”, “robocasting” and “3D printing” as descriptors. This search strategy was performed on PubMed (MEDLINE), Scopus and Cochrane Library, but also by hand search in relevant journals and throughout the selected papers. All the papers focusing on techniques for manufacturing customized bone scaffolds were reviewed. The 62 articles identified described 14 techniques (4 subtraction + 10 addition techniques). Scaffold fabrication techniques can be also be classified according to the time at which they are developed, into Conventional techniques and Solid Freeform Fabrication techniques. The conventional techniques are unable to control the architecture of the pore and the pore interconnection. However, current Solid Freeform Fabrication techniques allow individualizing and generating complex geometries of porosity. To conclude, currently SLA (Stereolithography), Robocasting and FDM (Fused deposition modeling) are promising options in customized bone regeneration.

The management of hip fractures is nowadays mainly performed in Orthogeriatric Units, one of whose fundamental tools is the application of geriatric scores. The purpose of this study is to establish the potential usefulness of Barthel Index, Katz Index, Lawton-Brody Index and Physical Red Cross Scale geriatric scores as predictors of survival rate and readmission rate in older patients after hip fracture surgery. We designed a prospective single-center observational study, including 207 older adults over age 65 who underwent hip fracture surgery in the first half of 2014 and followed up to September 2018. Cumulative survival and readmission rates were analyzed by Kaplan-Meier; group comparison, by Log-Rank and hazard ratio, by Cox regression. We found statistical differences (p < 0.001) for cumulative survival rate by every geriatric score analyzed (BI HR = 0.98 [0.97,0.99]; KI HR = 1.24 [1.13–1.37]; LBI HR = 1.25 [1.16, 1.36]; PCRS HR = 1.67 [1.37,2.04]). Furthermore, we could determinate an inflection point for survival estimation by Barthel Index (BI 0–55/60–100*, p < 0.001, HR = 2.37 [1.59,3.53]), Katz Index (KI A-B*/C-G, p < 0.001, HR = 2.66 [1.80, 3.93], and Lawton-Brody Index (LBI 0–3/4–8*, p < 0.001, HR = 3.40 [2.09,5.25]). We reveal a correlation of the Charlson Index (p = 0.002) and Katz Index (p = 0.041) with number of readmissions for the study period. The geriatric scores analyzed are related to the cumulative survival rate after hip fracture surgery for more than 4 years, independently of other clinical and demographic factors. Katz Index in combination with Charlson Index could also be a potential predictor of the number of readmissions after surgery for hip fracture patients.