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Influence of growth factors on tissue-engineered pediatric elastic cartilage
C A Arévalo-Silva1, Y Cao, M Vacanti
1Department of Anesthesiology, University of Massachusetts Medical Center, Worchester, USA.
Insights
Basic fibroblast growth factor significantly enhanced the growth of engineered pediatric human elastic cartilage in vitro and in vivo. This finding suggests potential clinical applications for generating large volumes of quality cartilage from small samples.
Area of Science:
- Regenerative Medicine
- Biomaterials Science
- Pediatric Orthopedics
Background:
- Tissue engineering aims to regenerate damaged tissues.
- Elastic cartilage regeneration is crucial for pediatric reconstructive surgery.
- Growth factors play a key role in cellular proliferation and differentiation.
Purpose of the Study:
- To evaluate the impact of specific growth factors on engineered pediatric human elastic cartilage.
- To assess the potential clinical applicability of growth factor-enhanced cartilage tissue engineering.
Main Methods:
- Pediatric auricular elastic cartilage specimens were used to isolate chondrocytes.
- Chondrocytes were cultured in vitro with basic fibroblast growth factor (bFGF), transforming growth factor beta (TGF-β), or both.
- Constructs were implanted subcutaneously in athymic mice for in vivo evaluation.
Main Results:
- Basic fibroblast growth factor (bFGF) significantly increased chondrocyte proliferation in vitro.
- In vivo, bFGF-treated constructs showed the largest size and heaviest weight.
- bFGF and control groups exhibited cartilage histology similar to native tissue, while TGF-β groups showed disorganization and fibrosis.
Conclusions:
- Basic fibroblast growth factor (bFGF) is the most effective growth factor for promoting pediatric elastic cartilage tissue engineering.
- bFGF holds promise for clinical applications requiring rapid generation of high-quality engineered cartilage from limited donor tissue.
Objective:
To investigate the influence of growth factors on tissue-engineered pediatric human elastic cartilage relative to potential clinical application.
Design:
Controlled study.
Subjects:
Eleven children ranging in age from 5 to 15 years provided auricular elastic cartilage specimens measuring approximately 1 x 1 x 0.2 cm and weighing approximately 100 mg.
Interventions:
Three million chondrocytes were plated into 4 groups of Ham F-12 culture medium: group 1, Ham F-12 culture medium only; no growth factors (control group); group 2, Ham F-12 culture medium and basic fibroblast growth factor; group 3, Ham F-12 culture medium and transforming growth actor beta; and group 4, Ham F-12 culture medium and a combination of both growth factors. At 3 weeks, the cells were harvested and mixed with a copolymer gel of polyethylene glycol and polypropylene oxide (Pluronic F-127). The cell solution was injected subcutaneously into athymic mice. The constructs were harvested at up to 22 weeks of in vivo culture and histologically analyzed.
Results:
The average number of cells generated in vitro was as follows: group 1, 12 million; group 2, 40 million; group 3, 7 million; and group 4, 35 million. Group 2 in vivo gross specimens were the largest and heaviest. Histologically, the control group and the basic fibroblast growth factor group (groups 1 and 2) exhibited characteristics compatible with normal auricular cartilage; groups 3 and 4 demonstrated cellular disorganization and moderate to severe fibrous tissue infiltration.
Conclusions:
Basic fibroblast growth factor demonstrates the greatest positive influence on the in vitro and in vivo growth of engineered pediatric human auricular cartilage. The results suggest that basic fibroblast growth factor has the potential for clinical application in which a goal will be to generate a large volume of tissue-engineered cartilage from a small donor specimen in a short period of time and of a quality similar to native human elastic cartilage.