Aesthetic medicine: Adipose (fat) tissue engineering using injectible hydrogels
Adipose tissue engineering
1. Reconstruction applications:
A. Congenital Anomaly : hemifacial microsomia, facial asymmetry
B. After Cancer Ablation –Breast reconstruction, Facial reconstruction, Depressed Scar after large
skin cancer excision(ex. melanoma)
C. Post-irradiation soft tissue atrophy
D. Post-burn scar contracture
E. Post-traumatic soft tissue deficiency
F. Soft tissue padding around joint area
G. Intractable skin ulcer from diabetes,ischemia, collagen diseases
2. Aesthetic applications:
A. Breast augmentation
B. Facial contouring
C. Sunken Upper eyelid
D. Dark Circle in Lower eyelid
E. Deepened Nasolabial fold
F. Temple Depression
G. Lip augmentation
H. Hand rejuvenation
I. Buttock augmentation
J. Penile augmentation
K. Depressed Scar
L. Anti-wrinkle effect, skin
Innovations and Advantages
Contour defects due to loss of soft tissue, mostly subcutaneous adipose tissue, are associated with trauma, tumor resection and congenital abnormalities. These affect patients not only cosmetically, but also affect the emotional well being of patients and may impair functions such as range of motion. Currently, several surgical approaches, including the use of autologous tissue flaps, free fat grafting, and the implantation of commercially available prosthetic materials are used to restore or replace a volume of adipose tissue. However, these treatment modalities present a number of challenges and limitations, such as donor site morbidity and volume loss over time.
Injectable soft tissue fillers are in high demand because there is a shorter recovery time, results are immediate, and injection is both safer and more cost-effective than surgical implantation. Autologous fat is the ideal soft-tissue filler; it is readily available, easy to harvest, and safe. However, consistent results are lacking because a majority of the injected fat tissue is resorbed.
Hyaluronic acid, collagen, polymethyl methacrylate spheres, and calcium hydroxyl apatite, and poly-L-lactic acid have all been used as tissue surrogates, due to the limitations of autologous solutions. But these commercially available artificial fillers also present potential limitations, including foreign body reaction, fibrous capsule contraction, distortion, suboptimal mechanical properties, migration, and long–term resorption.
Engineered tissue fillers can improve on these results by incorporating autologous cells in a delivery vehicle that provides structure, shape, and the proper 3-dimensional matrix for tissue and vascular ingrowth while the biomaterial degrades to leave a natural tissue. Researchers in Dr. Mooney’s laboratory engineered adipose tissue by combining a degradable alginate hydrogel system previously developed in his lab with commercially available cryopreserved human adipose stem cells(hADSCs).
Adipose-derived stem cells (ADSCs) are in many ways an ideal transplant cell because 1) they are highly expandable in monolayer culture; 2) can be readily induced to differentiate into adipocytes in vitro in response to well-established inductive conditions; 3) are easy to obtain from the subcutaneous fat of the patient; 4) available in relatively large quantities at harvest using a minimally invasive procedure; 5) can be readily cryopreserved, which confers many advantages for practitioners engaged in cell-based therapies, including allowing transport of cells, pooling of cells to reach a therapeutic dose, and allowing time for the completion of safety and quality control testing. A potential limitation of these cells in engineering tissues, though, is that they can readily spread from the recipient site if introduced without a carrier.
Alginates, a family of naturally occurring polysaccharides organized into copolymers, form hydrogels due to rapid cross-linking in the presence of divalent cations. Alginates are one class of hydrogel-forming material and have been widely utilized in tissue engineering and drug delivery application, because they are biocompatible, injectable and easily processed into a desired shape during gelation. These polymers have been used safely as a non-prescription medication for the treatment of hearburn and acid reflux (Gaviscon, Bisodol, Asilone), as a wound dressing materials (AlgicellTM, AlgiSiteTM, ComfeelPlusTM, KaltostatTM, SorbsanTM, and TegagenTM), and as an appetite suppressant for long-term weight loss. Degradability is a critical material property for many applications in tissue engineering , but typical alginate hydrogels degrade very slowly and in a poorly controlled manner.
Degradable alginate gels previously developed in the Mooney lab: The degradable alginate hydrogels can be made susceptible to hydrolysis, and thus readily degraded. These gels demonstrate ~80% mass loss in 40 days in vitro, with only small gel fragments remaining in vivo at 4 weeks. The Mooney lab demonstrated that these degradable alginate hydrogels can be used as a vehicle for preconditioned cryopreserved hADSCs to engineer adipose tissue in vivo.
Engineered adipose tissue in vivo: To engineer adipose tissue, hADSCs were first differentiated into adipogenic cells, and encapsulated in the degradable alginate hydrogels. Cell laden gels were then injected subcutaneously into the chest wall of mice, and a cell suspension without alginate served as control. After 10 weeks, specimens were harvested and analyzed morphologically, histologically and with immunoblotting of tissue extractions. Newly generated tissues were semitransparent and soft in all experimental mice, grossly resembling adipose tissue. Analysis using confocal live imaging, Immunohistochemisty and western blot analysis revealed that the newly generated tissue was adipose tissue. Their research demonstrates that degradable, injectable alginate hydrogels provide a suitable delivery vehicle for preconditioned cryopreserved hADSCs to engineer adipose tissue.
Kim, Woo Seob
Mooney, David J.
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Reference Harvard Case #4151