Tissue compatibility of two biodegradable tubular scaffolds implanted adjacent to skin or buccal mucosa in mice.
Radiation therapy for cancer in the head and neck region leads to a marked loss of salivary gland parenchyma, resulting in a severe reduction of salivary secretions. Currently, there is no satisfactory treatment for these patients. To address this problem, we are using both tissue engineering and gene transfer principles to develop an orally implantable, artificial fluid-secreting device. In the present study, we examined the tissue compatibility of two biodegradable substrata potentially useful in fabricating such a device. We implanted in Balb/c mice tubular scaffolds of poly-L-lactic acid (PLLA), poly-glycolic acid coated with PLLA (PGA/PLLA), or nothing (sham-operated controls) either beneath the skin on the back, a site widely used in earlier toxicity and biocompatibility studies, or adjacent to the buccal mucosa, a site quite different functionally and immunologically. At 1, 3, 7, 14, and 28 days postimplantation, implant sites were examined histologically, and systemic responses were assessed by conventional clinical chemistry and hematology analyses. Inflammatory responses in the connective tissue were similar regardless of site or type of polymer implant used. However, inflammatory reactions were shorter and without epithelioid and giant cells in sham-operated controls. Also, biodegradation proceeded more slowly with the PLLA tubules than with the PGA/PLLA tubules. No significant changes in clinical chemistry and hematology were seen due to the implantation of tubular scaffolds. These results indicate that the tissue responses to PLLA and PGA/PLLA scaffolds are generally similar in areas subjacent to skin in the back and oral cavity. However, these studies also identified several potentially significant concerns that must be addressed prior to initiating any clinical applications of this device.
Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
D J
DJ
Aframian
R S
RS
Redman
S
S
Yamano
J
J
Nikolovski
E
E
Cukierman
K M
KM
Yamada
M F
MF
Kriete
W D
WD
Swaim
D J
DJ
Mooney
B J
BJ
Baum
D000818:Animals; D001672:Biocompatible Materials; D004343:Drug Implants; D005260:Female; D007249:Inflammation / Q000378:metabolism; D019344:Lactic Acid / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects; D011091:Polyesters; D011100:Polyglycolic Acid / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D019736:Prostheses and Implants; D012867:Skin / Q000166:cytology / Q000187:drug effects
D001672:Biocompatible Materials; D004343:Drug Implants; D011091:Polyesters; D011108:Polymers; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)