Treatment of Nonunion Fractures With Mesenchymal Stromal Cells (MSCs)

Study Overview
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Brief Summary
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The goal of this study is to evaluate the bone regeneration capacity of BM-MSC (Bone marrow mesenchymal stromal cells), in patients with nonunion. BM-MSC cultured are seeded on a collagen scaffold, included into autologous platelet-rich plasma (PRP) clot, and implanted in the nonunion bone defect.

Detailed Description
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Nonunion (pseudoarthrosis) is one of the most serious complications of bone fracture. Even though different treatments have been used to repair nonunion bone defects, most of them have limitations, like morbidities, limited supply, frequent treatment failure, and high cost. Based on the knowledge that MSC have multipotential capacity of differentiation into bone, cartilage, fat, and endothelial cells, and also, play a key role in the process of bone formation and fracture repair. In this study, we evaluated the use the bone regeneration capacity of autologous or allogeneic BM-MSC, as a potential therapeutic strategy to induce formation of new bone tissue and fracture healing. A bioengineering construct, constituted by MSCs and a collagen scaffold, is incorporated into platelet rich plasma (PRP) clot, wich is implanted at the nonunion site defect.

Official Title
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Treatment of Nonunion After Fractures (Pseudoartrosis) Using Mesenchymal Stromal Cells (MSCs)

Conditions
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Pseudoarthrosis of Bone, Pseudarthrosis, Non Union Fracture, Nonunion Bone Fracture

Intervention / Treatment
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* Biological: Transplantation of autologous MSCs in nonunion fracture
* Biological: Transplantation of allogeneic MSCs in nonunion fracture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-traumatic nonunion diagnosis (Pseudoarthrosis) with or without previous ortopaedic treatment Patients with or without previous orthopaedic treatment Presence of nonunion 9 month or more Ossification failure in the non-union area, with an approximate size of 0.5 to 4 cm length Exclusion Criteria: Evidence of infection at the nonunion site (Osteomielitis) Evidence of cutaneous lesion at the site of pseudoartrosis Viral hepatitis B and C, HIV infection, syphilis and other viral and bacterial infections Autoimmune diseases Neoplastic diseases Pregnancy Major metabolic disorders Treatment with steroids Other conditions or circumstances that compromise the study participation according to medical criteria

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologuos MSCs transplantation in nonunion defects<br>Autologuos MSCs harvested and cultured in osteogenic medium are seeded on collagen scaffold, and mixed with autologous rich plasma clot. The MSCs construct (MSCs/Col/PRP clot), is implanted in the nonunion defect. | Biological: Transplantation of autologous MSCs in nonunion fracture<br>* At surgery, fibrotic tissue is removed from the nonunion sites. MSCs/Col/PRP clots are implanted in the site of nonunion. Patients received conventional orthopedic treatment as they needed (osteotomy, external and/or internal fixation systems, etc.)<br>|
| Experimental: Allogeneic MSCs transplantation in nonunion defects<br>Allogeneic MSCs harvested and cultured in osteogenic medium are seeded on collagen scaffold, and mixed with autologous rich plasma clot. The MSCs construct (MSCs/Col/PRP clot), is implanted in the nonunion defect. | Biological: Transplantation of allogeneic MSCs in nonunion fracture<br>* At surgery, fibrotic tissue is removed from the nonunion sites. MSCs/Col/PRP clots are implanted in the site of nonunion. Patients received conventional orthopedic treatment as they needed (osteotomy, external and/or internal fixation systems, etc.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical evaluation | Time of surgical wound evolution, surgically intervened limb evolution, movility | Baseline, 1 and 7 days. 1, 2 and 6 months. 1 and 2 years | 
| Bone consolidation | Time of development changes in bone consolidation by radiological studies | Baseline, 1 and 7 days. 1, 2 and 6 months. 1 and 2 years |