Tissue Compatibility of Two Biodegradable Tubular Scaffolds Implanted Adjacent to Skin or Buccal Mucosa in Mice

Abstract

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.

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

“…Numerous studies have focused on feasibility of using nanofibers or hydrogel-based scaffolds. [15][16][17][18][19][20][21][22][23][24][25] Although a few studies have translated their findings in vivo, 16,17,23 no study to date has demonstrated that the tissue developed on or within biomaterials contributes to restoration of gland function. To overcome these limitations, we propose use of poly(ethylene glycol) (PEG) hydrogels for salivary gland cell transplantation.…”

Re-engineering Primary Epithelial Cells from Rhesus Monkey Parotid Glands for Use in Developing an Artificial Salivary Gland

“…As we previously showed, for in situ testing of a functional artificial salivary gland, a large animal is required, as is an autologous graft cell. 11,16 As shown herein, rhesus parotid glands provide an excellent model for such studies. Each individual animal could provide a cell source via a biopsy of the tail region of the parotid gland with minimal morbidity.…”

“…[13][14][15] A significant hurdle in developing this device is the choice of an appropriate model for testing a prototype in vivo, because conventional rodent models are too small for effective testing of the in situ placement and function of an artificial salivary gland. 16 In the present study, we used a non-human primate tissue, parotid glands from rhesus monkeys, as a cell source. Rhesus monkeys provide a sizable animal suitable for eventual in vivo testing of a prototype device.…”

Overview on Biocompatibilities of Implantable Biomaterials

“…No significant changes in clinical chemistry and hematology were seen due to the implantation of tubular scaffolds. [153]. It was reported that, after the PLLA segments were swallowed in vivo by phagocytes, cell damage and cell death were obvious.…”