Percutaneous administration of allogeneic bone-forming cells for the treatment of delayed unions of fractures: a pilot study

Abstract Background Overall, 5–10% of fractures result in delayed unions or non-unions, causing major disabilities and a huge socioeconomic burden. Since rescue surgery with autologous bone grafts can cause additional challenges, alternative treatment options have been developed to stimulate a deficient healing process. This study assessed the technical feasibility, safety and preliminary efficacy of local percutaneous implantation of allogeneic bone-forming cells in delayed unions of long bone fractures. Methods In this phase I/IIA open-label pilot trial, 22 adult patients with non-infected delayed unions of long bone fractures, which failed to consolidate after 3 to 7 months, received a percutaneous implantation of allogeneic bone-forming cells derived from bone marrow mesenchymal stem cells (ALLOB; Bone Therapeutics) into the fracture site (50 × 106 to 100 × 106 cells). Patients were monitored for adverse events and need for rescue surgery for 30 months. Fracture healing was monitored by Tomographic Union Score (TUS) and modified Radiographic Union Score. The health status was evaluated using the Global Disease Evaluation (GDE) score and pain at palpation using a visual analogue scale. The presence of reactive anti-human leukocyte antigen (HLA) antibodies was evaluated. Results During the 6-month follow-up, three serious treatment-emergent adverse events were reported in two patients, of which two were considered as possibly treatment-related. None of the 21 patients in the per-protocol efficacy population needed rescue surgery within 6 months, but 2/21 (9.5%) patients had rescue surgery within 30 months post-treatment. At 6 months post-treatment, an improvement of at least 2 points in TUS was reached in 76.2% of patients, the GDE score improved by a mean of 48%, and pain at palpation at the fracture site was reduced by an average of 61% compared to baseline. The proportion of blood samples containing donor-specific anti-HLA antibodies increased from 8/22 (36.4%) before treatment to 13/22 (59.1%) at 6 months post-treatment, but no treatment-mediated allogeneic immune reactions were observed. Conclusion This pilot study showed that the percutaneous implantation of allogeneic bone-forming cells was technically feasible and well tolerated in patients with delayed unions of long bone fractures. Preliminary efficacy evidence is supporting the further development of this treatment. Trial registration NCT02020590. Registered on 25 December 2013. ALLOB-DU1, A pilot Phase I/IIa, multicentre, open proof-of-concept study on the efficacy and safetyof allogeneic osteoblastic cells (ALLOB®) implantation in non-infected delayed-union fractures.

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Biomechanical Evaluation Method to Optimize External Fixator Configuration in Long Bone Fractures—Conceptual Model and Experimental Validation Using Pilot Study

Applied Sciences ◽

10.3390/app11188481 ◽

2021 ◽

Vol 11 (18) ◽

pp. 8481

Author(s):

Thiran Sellahewa ◽

Charitha Weerasinghe ◽

Pujitha Silva

Keyword(s):

Mechanical Properties ◽

Pilot Study ◽

Evaluation Method ◽

Bone Fractures ◽

Element Model ◽

Fracture Site ◽

System Stability ◽

Long Bone ◽

Use Case ◽

Non Union

External fixation is a commonly used method in stabilizing fracture sites. The performance of the fixator depends on how it affects the mechanical properties of the fracture site and is governed by parameters like the fixator type and fixator configuration. Identifying ideal configurations prior to surgery will help surgeons in planning the procedure, limiting the possibility of complications such as non-union. In this study, a framework has been proposed as a surgical pre-planning tool, to assist surgeons compare mechanical properties of a fracture site under different fixator configurations, and thereby identify the optimum solution. A computational tool was identified as the best method for this purpose. Cost and time of computation were given special consideration to reduce complexity in clinical settings. A pilot study was conducted on a section of the proposed framework, where the aim was to understand the feasibility of implementation. In the pilot study, a unilateral uni-planar fixator on a simple diaphyseal transverse fracture was analyzed. During the pilot study the selected fixator was tested and a few models were developed to assess system stability. The models were then compared to identify the optimum model that could be used with the proposed framework. The proposed framework provided a suitable solution for the use case and out of the models developed the simplified finite element model was identified as the best option for the use case.

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Comparison of Outcome of Bone Autograft and Allograft in Union of Long Bone Fractures

Acta Medica Bulgarica ◽

10.2478/amb-2021-0017 ◽

2021 ◽

Vol 48 (2) ◽

pp. 13-18

Author(s):

H. Valiyollahpoor-Amiri ◽

S. M. Esmaeilnejad-Ganji ◽

R. Jokar ◽

B. Baghianimoghadam ◽

S. Kamali-Ahangar ◽

...

Keyword(s):

Range Of Motion ◽

Bone Fractures ◽

Bone Allograft ◽

Fracture Site ◽

Lower Limbs ◽

Long Bone ◽

Long Bone Fractures ◽

Surgical Methods ◽

Long Bone Fracture ◽

Bone Autograft

Abstract Background and Purpose There are few studies addressing the rate of application of bone allograft and its use; hence, the present study aimed to compare the clinical outcomes of using bone allograft and autograft in patients with long bone fracture. Method In this clinical trial study, all patients who underwent bone graft surgery with the diagnosed long bone fractures of upper and lower limbs at Shahid Beheshti Hospital were included in the research. Patients were divided into two groups, autograft and allograft, according to type of treatment. They were evaluated for their union, complications, and range of motion. Results In the present study, 124 people were studied. Among them, 100 patients were eligible and included in the study. The allograft and autograft groups did not have any statistical significant differences in terms of age, sex, location, causes of fracture, and surgical methods. Results of the present research on patients in terms of fracture site indicated that there was no significant relationship between the two groups in rate of union (P = 0.18). Allograft and autograft had no difference in terms of complications. Studied range of motion indicated that patients were not different in terms of their ranges of motion. Conclusion Based on findings of the present study, allograft could be a suitable substitute for the autograft. The two graft methods were similar in terms of complications, union, and ranges of motion.

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