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Williams D.F.,Wake Forest Institute of Regenerative Medicine
Biomaterials | Year: 2011

This paper constitutes the judgment on the four-paper debate in the same issue of this journal on the motion that ''the use of short synthetic adhesion peptides, like RGD, is the best approach in the design of biomaterials that guide cell behavior for regenerative medicine and tissue engineering" It is concluded that this motion is carried on the basis that the concept of installing multifunctionality and modularity in peptides is the more powerful concept, coupled with the potential attractiveness of retaining a chemically defined product, without any possibilities of disease transmission, and relative inexpensiveness and clearer regulatory pathways. © 2011 Elsevier Ltd.

Williams D.F.,Wake Forest Institute of Regenerative Medicine
Tissue Engineering - Part A | Year: 2014

The development of biomaterials for use in tissue engineering processes has not so far followed a scientifically valid pathway; there have been no properly constituted specifications for these biomaterials, whose choice has often been dictated by the perceived need to comply with prior FDA approval for use of the materials in nontissue engineering applications. This short essay discusses the difficulties that have resulted in this approach and provides both conceptual and practical solutions for the future, based on sound principles of biocompatibility and the need to use tissue engineering templates that replicate the niche of the target cells. © 2014, Mary Ann Liebert, Inc. 2014.

Ebrahim Attia A.B.,Institute Of Bioengineering And Nanotechnology, Singapore | Yang C.,Institute Of Bioengineering And Nanotechnology, Singapore | Tan J.P.K.,Institute Of Bioengineering And Nanotechnology, Singapore | Gao S.,Institute Of Bioengineering And Nanotechnology, Singapore | And 3 more authors.
Biomaterials | Year: 2013

This study was aimed to investigate the effect of kinetic stability on biodistribution and antitumor efficacy of drug-loaded biodegradable polymeric micelles. Four diblock copolymers of acid- and urea-functionalized polycarbonate (i.e. PAC and PUC) and poly(ethylene glycol) (PEG) with the same polycarbonate length and two different PEG molecular weights (Mn: 5 kDa and 10 kDa), i.e. 5K PEG-PAC, 10K PEG-PAC, 5K PEG-PUC and 10K PEG-PUC, were synthesized via organocatalytic living ring-opening polymerization using methoxy PEG as a macroinitiator. These polymers were employed to prepare 5K PEG-PAC/5K PEG-PUC and 10K PEG-PAC/10K PEG-PAC mixed micelles via urea-acid hydrogen bonding. An amine group-containing anticancer drug, doxorubicin (DOX) was loaded into the mixed micelles via a self-assembly process. DOX-loaded 5K and 10K PEG mixed micelles had particle sizes of 66 and 87 nm respectively with narrow size distribution (polydispersity index: 0.12), and DOX loading levels were 28.9 and 22.8% in weight. DOX-loaded 5K PEG mixed micelles had greater kinetic stability than DOX-loaded 10K PEG mixed micelles due to stronger hydrophobicity of 5K PEG block copolymers. The results of in vitro release studies showed that DOX release was sustained without obvious initial burst release. The DOX-loaded mixed micelles effectively suppressed the proliferation of HepG2 and 4T1 cells. The in vivo studies conducted in a 4T1 mouse breast cancer model demonstrated that the mixed micelles were preferably transported to the tumor with the 5K PEG mixed micelles accumulating in the tumor more rapidly to a larger extent than 10K PEG mixed micelles, and DOX-loaded 5K PEG mixed micelles with greater kinetic stability inhibited tumor growth more effectively than free DOX and DOX-loaded 10K PEG mixed micelles without causing significant body weight loss or cardiotoxicity. The 5K PEG mixed micelles with sizes below 100 nm and narrow size distribution as well as excellent kinetic stability holds great potential as a delivery carrier for amine group-containing anticancer drugs. © 2013 Elsevier Ltd.

Krane L.S.,Wake forest University | Hemal A.K.,Wake forest University | Hemal A.K.,Wake Forest Institute of Regenerative Medicine
Current Opinion in Urology | Year: 2012

Purpose of Review: Surgeon-controlled, robotic-assisted, ureteral reconstructive and ablative surgery is being performed routinely for both benign and malignant pathology at centers possessing this technology in their armamentarium. The aim of this review is to detail the options for surgeon-controlled robotic management of ureteral pathology and evaluate the developments in the last 2 years. Recent Findings: Surgeon-controlled robotic management of ureteric pathology involving all parts of the ureter with varying cause has been reported. Proximally, ureteral strictures and symptomatic retrocaval ureters have been repaired with long-term follow-up demonstrating resolution of obstruction. Ureterolysis and other mid-ureteral pathology have been treated with durable function results. Transitional cell carcinoma of the renal pelvis or distal ureter has been extirpated with successful oncologic outcomes. Reimplantation of refluxing ureters in children has been demonstrated to provide similar results of open surgery. Summary: Surgeon-controlled, robotic-assisted ureteral surgery is well tolerated, feasible, and effective for ablative and reconstructive indications with minimal complications. Knowledge of anatomy, pathology, experience of surgical team, and appropriate preoperative patient selection augmented with proper port placement to provide excellent exposure is critical to provide optimal outcomes. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Gu X.,Nantong University | Ding F.,Nantong University | Williams D.F.,Wake Forest Institute of Regenerative Medicine
Biomaterials | Year: 2014

Tissue engineered nerve grafts (TENGs) have emerged as a potential alternative to autologous nerve grafts, the gold standard for peripheral nerve repair. Typically, TENGs are composed of a biomaterial-based template that incorporates biochemical cues. A number of TENGs have been used experimentally to bridge long peripheral nerve gaps in various animal models, where the desired outcome is nerve tissue regeneration and functional recovery. So far, the translation of TENGs to the clinic for use in humans has met with a certain degree of success. In order to optimize the TENG design and further approach the matching of TENGs with autologous nerve grafts, many new cues, beyond the traditional ones, will have to be integrated into TENGs. Furthermore, there is a strong requirement for monitoring the real-time dynamic information related to the construction of TENGs. The aim of this opinion paper is to specifically and critically describe the latest advances in the field of neural tissue engineering for peripheral nerve regeneration. Here we delineate new attempts in the design of template (or scaffold) materials, especially in the context of biocompatibility, the choice and handling of support cells, and growth factor release systems. We further discuss the significance of RNAi for peripheral nerve regeneration, anticipate the potential application of RNAi reagents for TENGs, and speculate on the possible contributions of additional elements, including angiogenesis, electrical stimulation, molecular inflammatory mediators, bioactive peptides, antioxidant reagents, and cultured biological constructs, to TENGs. Finally, we consider that a diverse array of physicochemical and biological cues must be orchestrated within a TENG to create a self-consistent coordinated system with a close proximity to the regenerative microenvironment of the peripheral nervous system. © 2014 Elsevier Ltd.

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