Anthony J. Bullock

Tissue-engineered buccal mucosa for substitution urethroplasty.

To develop tissue‐engineered buccal mucosa (TEBM) for use in substitution urethroplasty, as urethral reconstruction is limited by the amount and type of tissue that is available for grafting, and BM has become the favoured tissue for use as a urethral substitute in the last decade.

Decellularization and sterilization of porcine urinary bladder matrix for tissue engineering in the lower urinary tract

BACKGROUND Several synthetic and natural matrices have been described for tissue engineering of bladder but there is little information on the effects of processing on their subsequent mechanical performance or interaction with human cells. AIM Our aim was to assess the effects of delamination, decellularization and sterilization on the mechanical properties of porcine urinary bladder matrix (UBM) and to then assess the ability of the UBM to act as a scaffold for reconstruction with human bladder cells. METHODS A total of 20 porcine bladders were assessed before and after mechanical delamination and four porcine bladders were followed at every stage through a comparison of several decellularization and terminal sterilization methodologies examining histological and mechanical characteristics. The sterile UBM was seeded with normal human urothelial and bladder stromal cells either as a simultaneous coculture, or with stromal cells followed by urothelial cells. RESULTS Mechanical delamination, physical rinsing of the resulting bladder stroma in hypotonic buffer, 0.1% sodium dodecyl sulfate solution and 0.1% peracetic acid resulted in an UBM with acceptable mechanical properties capable of supporting urothelial and bladder stromal cells. Terminal sterilization with ethylene oxide resulted in considerable stiffening of the matrix simultaneous coculture and layered seeding of scaffolds with stromal cells followed by epithelial cells gave similar results with good initial urothelial attachment (followed by loss of cells later) and slow stromal cell penetration. CONCLUSION We describe a decellularized sterilized porcine UBM with acceptable mechanical properties that shows promise as a scaffold for producing an in vitro tissue-engineered bladder patch material for lower urinary tract reconstruction. Future work now needs to focus on the conditions for achieving secure epithelial attachment.

Randomized, controlled, single-blind study on use of autologous keratinocytes on a transfer dressing to treat nonhealing diabetic ulcers

AIM To compare the rate of healing of diabetic neuropathic ulcers using cultured autologous keratinocytes delivered on chemically defined transfer discs (Myskin) (active treatment) versus healing obtained with cell-free discs (placebo). MATERIALS AND METHODS After a 4-week lead-in period patients (randomly assigned) received active or placebo treatments weekly for 6 weeks. All patients then received active treatments for a maximum of 12 treatments where required. Altogether, 16 patients with a total of 21 ulcers resistant to conventional therapy were recruited from four specialist diabetic centers in three cities. RESULTS All 21 ulcers were treated and of these ten healed and eight improved, with two failing to respond (one ulcer was lost due to autoamputation). For analysis according to the study criteria, however, only the 12 patients with 12 index ulcers who completed treatment protocols were eligible - five in the placebo group and seven in the active group. Of these, five ulcers healed completely and seven were reduced by more than 50%. Complete healing took a median of ten active applications. CONCLUSIONS Repeated regular applications of the patients keratinocytes, delivered on the carrier dressing, initiated wound healing in ulcers resistant to conventional therapy, with 18 out of 21 ulcers responding. The healing observed did not appear attributable to patient recruitment or the cell-free carrier dressing but to the delivery of the cultured cells.

Developing biodegradable scaffolds for tissue engineering of the urethra

What’s known on the subject? and What does the study add?

Investigation of keratinocyte regulation of collagen I synthesis by dermal fibroblasts in a simple in vitro model

Background  Hypertrophic scarring and skin graft contracture are major causes of morbidity after burn injuries. A prominent feature is excessive fibroplasia with accumulation of increased fibrillar collagen relative to normal scar tissue. The application of split‐thickness skin grafts or cultured epithelial autografts to burn wounds is known to reduce scarring and contraction.

Comparison of candidate scaffolds for tissue engineering for stress urinary incontinence and pelvic organ prolapse repair

To identify candidate materials which have sufficient potential to be taken forward for an in vivo tissue‐engineering approach to restoring the tissue structure of the pelvic floor in women with stress urinary incontinence (SUI) or pelvic organ prolapse (POP).

Transglutaminase inhibitors induce hyperproliferation and parakeratosis in tissue‐engineered skin

Background  The transglutaminase (TG) family consists of eight distinct isoforms. TG types 1, 3 and 5 play a major role in normal skin development, with TG2 also being elevated during dermal wounding. TG1, 3 and 5 are responsible for the cross‐linking of keratin precursors and formation of the cornified envelope during keratinocyte differentiation. TG2 may play a role in keratinocyte basement membrane cross‐linking. Abnormal TG expression has been demonstrated in Darier disease, Netherton syndrome, psoriasis and lamellar ichthyosis. During a recent investigation of skin contraction in tissue‐engineered skin, transglutaminase inhibitors were found to produce hyperproliferation and parakeratosis.

Are biomechanical properties predictive of the success of prostheses used in stress urinary incontinence and pelvic organ prolapse? A systematic review

Progressive weakness in pelvic floor tissues is extremely common and leads to the distressing problems of stress urinary incontinence (SUI) and pelvic organ prolapse (POP). There has been extensive work on a vast array of materials spanning synthetics, autografts, allografts, and xenografts. Uniaxial testing of materials has been used to predict their success and rates of erosion. We aimed to compare the uniaxial properties of prostheses to native paravaginal tissue and correlate these to their success and erosion rates.

Developing a tissue engineered repair material for treatment of stress urinary incontinence and pelvic organ prolapse—which cell source?

Synthetic non‐absorbable meshes are widely used to augment surgical repair of stress urinary incontinence (SUI) and pelvic organ prolapse (POP); however, there is growing concern such meshes are associated with serious complications. This study compares the potential of two autologous cell sources for attachment and extra‐cellular matrix (ECM) production on a biodegradable scaffold to develop tissue engineered repair material (TERM).

Tissue engineering airway mucosa: A systematic review

Effective treatments for hollow organ stenosis, scarring, or agenesis are suboptimal or lacking. Tissue‐engineered implants may provide a solution, but those performed to date are limited by poor mucosalization after transplantation. We aimed to perform a systematic review of the literature on tissue‐engineered airway mucosa. Our objectives were to assess the success of this technology and its potential application to airway regenerative medicine and to determine the direction of future research to maximize its therapeutic and commercial potential.