Reshapable Hydrogel Tissue Expander

描述（由申请人提供）：对于牙科和其他应用，非常需要能够在植入时由外科医生重塑以适应空隙的自我填充组织扩张器。Akina最近使用其基于水凝胶的可重塑肿胀组织扩张器（Restiex(R)）完成了初始II期研究。该研究验证了Restiex在大鼠皮肤和狗粘膜中产生附加组织的功能。我们随后对狗的研究表明，Restiex在狗体内成功形成新组织所必需的特性与在大鼠研究中发现的特性非常不同。重要的是，我们目前的研究提供了成功插入、膨胀和取出膨胀器所需的Restiex特性的重要信息。这个延续的II期研究是合成具有从狗研究中确定的三个关键特性的水凝胶。控制膨胀动力学和膨胀压力对于防止缺血是必不可少的，缺血会导致膨胀器坏死和爆发。为了在膨胀结束时方便地将膨胀器整体取出，控制好机械强度是必要的。这项研究的合作研究者Clark T. Barco博士将在我们的狗模型中测试具有定制特性的新型水凝胶组织扩张器的安全性和有效性。在这个II期续期研究结束时，我们将有Restiex扩张剂的最终配方，准备进行临床测试和商业化。本二期更新项目有三个具体目标：(1)合成具有可控膨胀动力学、膨胀压力和机械强度的可重塑组织扩张器；(2)验证组织扩张器在犬口腔内模型中的安全性和有效性；(3)建立膨胀剂的体外性能与体内性能的相关性。第二阶段项目的更新将使Akina充分开发其基于水凝胶的Restiex，该产品比目前市售的组织扩张剂具有实质性优势。没有现有的组织扩张器允许外科医生重塑，也允许控制肿胀动力学和扩张压力。凭借这些优势，Akina的Restiex有望立即对该领域产生影响。在这个更新的二期项目结束时，Akina将能够生产安全有效的新型组织扩张剂，为人体临床试验做好准备。

DESCRIPTION (provided by applicant): For dental and other applications there is a great need for self-filling tissue expanders with the capacity to be reshaped to fit the void by the surgeon at time of implantation. Akina recently completed an initial Phase II study using its hydrogel-based reshapable swelling tissue expanders (Restiex(R)). The study validated the function of Restiex to generate additional tissue of rat skin as well as of dog mucosa. Our subsequent dog study indicated that the properties of Restiex necessary for successful new tissue formation in dogs were very different from the properties identified from the rat study. Importantly, our current study has provided vital information on the Restiex properties required for successful insertion, expansion, and removal of the expander. This continuation Phase II study is to synthesize hydrogels possessing three critical properties identified from the dog studies. Controlling the swelling kinetics and expansion pressure is essential in preventing ischemia which causes necrosis and eruption of the expander. Controlling the mechanical strength is necessary for easy removal of the expander in one piece at the end of the expansion. The new hydrogel tissue expanders with tailor-made properties will be tested in our dog model for safety and effectiveness by Dr. Clark T. Barco, a co-investigator of this study. At the end of this Phase II renewal study, we will have the final formulation of Restiex expanders ready for clinical testing and commercialization. There are three specific aims of this Phase II renewal project: (1) to synthesize reshapable tissue expanders with controllable swelling kinetics, expansion pressure, and mechanical strength; (2) to validate safety and efficacy of tissue expanders in the intraoral dog model; and (3) to establish correlation between in vitro expander properties and in vivo performances. The renewed Phase II project will allow Akina to fully develop its hydrogel-based Restiex that has substantial advantages over current commercially available tissue expanders. No existing tissue expanders allow reshaping by a surgeon and also allow for the controlled swelling kinetics and expansion pressure. With these advantages, Akina's Restiex is expected to have immediate impact to the field. At the end of this renewal Phase II project, Akina will be able to produce safe and effective novel tissue expanders that are ready for human clinical trials.