Fat Grafts With Adipose-derived Regenerative Cells for Soft Tissue Reconstruction in Children

Study Overview
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Brief Summary
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Although first reports of the clinical use of adipose-derived regenerative cells (ADRC) suggest that this approach may be feasible and effective for soft tissue augmentation, there is a lack of randomized, controlled clinical trials in the literature. Hence, this study aimed to investigate whether a novel protocol for isolation of ADRC and their use in combination with fat tissue improve the long-term retention of the grafts in paediatric patients with craniofacial microsomia.

Detailed Description
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To overcome problems associated with fat grafting, such as unpredictable clinical results and a low rate of graft survival, many innovative efforts and refinements of surgical techniques have been reported. For example, condensation of living tissue and removal of unnecessary components have been performed by centrifugation, filtration or gravity sedimentation; external mechanical force has been used to expand the recipient tissue as well as the overlying skin envelope; and a recent experimental study has suggested that repeated local injections of erythropoietin might enhance retention of grafted fat. Based on the finding that aspirated fat tissue contains a much smaller number of adipose-derived regenerative cells (ADRC) compared with intact tissue and that these cells play pivotal roles in the adipose tissue remodeling after lipoinjection, the supplementation of fat grafts with stromal vascular fraction isolated from adipose portion of liposuction aspirates has been proposed as a method to compensate its relative deficiency of ADRC. In the literature, there are at least three experimental studies demonstrating that supplementation of adipose progenitor cells enhances the volume or weight of surviving adipose tissue, and first reports of the clinical use of ADRC suggest that this approach may be feasible and effective for soft tissue augmentation. However, since these studies represent level of evidence IV, which correspond to the publication of case series, there is a lack of randomized, controlled clinical trials comparing this method to current standard techniques. Hence, this study aimed to fill this gap by investigating whether a novel protocol for isolation of ADRC and their use in combination with fat tissue improve the long-term retention of the grafts in paediatric patients with craniofacial microsomia.

Official Title
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Fat Grafts Supplemented With Adipose-derived Regenerative Cells for Soft Tissue Reconstruction in Children With Craniofacial Microsomia

Conditions
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Craniofacial Microsomia

Intervention / Treatment
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* Procedure: Fat grafts supplemented with ADRC
* Procedure: Structural fat grafting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unilateral craniofacial microsomia 10 to 18 years old Phenotype: (M0, M1 or M2) and (S1 or S2) according to the OMENS-Plus classification Exclusion Criteria: Previous facial soft tissue surgery Absence of fat donor site

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, controlled, clinical trial with 2 parallel comparison groups
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: With ADRC<br>Supplementation of fat grafts with ADRC | Procedure: Fat grafts supplemented with ADRC<br>* Isolation of ADRC from fat aspirates and its use for supplementation of fat grafts.<br>|
| Active Comparator: Structural<br>Structural fat grafting | Procedure: Structural fat grafting<br>* Fat grafts without supplementation of ADRC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volumetric analysis of both hemifaces | Preoperative and 1, 3 and 6-months postoperative 3D-photogrammetry will be performed for volumetric measurements of both hemifaces using Vectra H1 software. Volumetric augmentation will be noticed for each patient by comparing the change between volumes of affected and unaffected hemifaces in the preoperative and 1, 3 and 6 months postoperative periods, which will be considered the retention volume. The percentage of fat graft survival will be determined as a ratio of the retention volume to the preoperative difference between volumes of affected and unaffected hemifaces. | Preoperative, 1 month postoperative, 3 months postoperative and 6 months postoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of viable cells | Immediately after the surgical procedure the number of viable cells isolated before and after the supplementation of the grafts will be counted using the trypan blue dye exclusion assay in a Neubauer chamber using the light microscope Nikon Eclipse TS100 (Nikon Instruments Inc., NY, USA). Next, immunophenotype characterization of cell populations on passage 1 will be done by flow cytometric analysis with the anti-human antibodies CD29, CD31, CD45, CD90, CD73 and CD105 (Becton, Dickinson and Company, NJ, USA) in a Guava EasyCyte flow cytometer running the Guava Express Plus software (Guava Technologies Hayward, CA, USA). | Intraoperative and immediate postoperative period |