Department of Diagnostic and Biomedical Sciences, School of Dentistry, UTHealth Science Center at Houston, Houston, TX 77054, United States; Department of Bioengineering, Rice University, Houston, TX 77005, United States.
Department of Orthodontics, School of Dentistry, UTHealth Science Center at Houston, Houston, TX 77054, United States.
Acta Biomater. 2022 Jan 15;138:1-20. doi: 10.1016/j.actbio.2021.10.056. Epub 2021 Nov 4.
This review explores the evolution of the use of hydrogels for craniofacial soft tissue engineering, ranging in complexity from acellular injectable fillers to fabricated, cell-laden constructs with complex compositions and architectures. Addressing both in situ and ex vivo approaches, tissue restoration secondary to trauma or tumor resection is discussed. Beginning with relatively simple epithelia of oral mucosa and gingiva, then moving to more functional units like vocal cords or soft tissues with multilayer branched structures, such as salivary glands, various approaches are presented toward the design of function-driven architectures, inspired by native tissue organization. Multiple tissue replacement paradigms are presented here, including the application of hydrogels as structural materials and as delivery platforms for cells and/or therapeutics. A practical hierarchy is proposed for hydrogel systems in craniofacial applications, based on their material and cellular complexity, spatial order, and biological cargo(s). This hierarchy reflects the regulatory complexity dictated by the Food and Drug Administration (FDA) in the United States prior to commercialization of these systems for use in humans. The wide array of available biofabrication methods, ranging from simple syringe extrusion of a biomaterial to light-based spatial patterning for complex architectures, is considered within the history of FDA-approved commercial therapies. Lastly, the review assesses the impact of these regulatory pathways on the translational potential of promising pre-clinical technologies for craniofacial applications. STATEMENT OF SIGNIFICANCE: While many commercially available hydrogel-based products are in use for the craniofacial region, most are simple formulations that either are applied topically or injected into tissue for aesthetic purposes. The academic literature previews many exciting applications that harness the versatility of hydrogels for craniofacial soft tissue engineering. One of the most exciting developments in the field is the emergence of advanced biofabrication methods to design complex hydrogel systems that can promote the functional or structural repair of tissues. To date, no clinically available hydrogel-based therapy takes full advantage of current pre-clinical advances. This review surveys the increasing complexity of the current landscape of available clinical therapies and presents a framework for future expanded use of hydrogels with an eye toward translatability and U.S. regulatory approval for craniofacial applications.
这篇综述探讨了水凝胶在颅面软组织工程中的应用演变，涵盖了从无细胞可注射填充剂到具有复杂成分和结构的细胞负载构建体的制造。讨论了创伤或肿瘤切除后组织的修复。从相对简单的口腔黏膜和牙龈上皮开始，然后转移到更具功能性的单位，如声带或具有多层分支结构的软组织，如唾液腺，本文提出了各种方法来设计受天然组织组织启发的功能驱动结构。这里提出了多种组织替代范例，包括将水凝胶用作结构材料和用作细胞和/或治疗剂的递送平台。根据其材料和细胞复杂性、空间顺序和生物货物，提出了用于颅面应用的水凝胶系统的实用层次结构。该层次结构反映了美国食品和药物管理局 (FDA) 在将这些系统商业化用于人体之前规定的监管复杂性。从简单的生物材料注射器挤出到用于复杂结构的基于光的空间图案化，广泛的可用生物制造方法都在 FDA 批准的商业疗法的历史中进行了考虑。最后，该综述评估了这些监管途径对颅面应用有前途的临床前技术转化潜力的影响。
虽然许多市售的基于水凝胶的产品用于颅面区域，但大多数都是简单的配方，要么用于美容目的的局部应用，要么用于注射到组织中。学术文献预览了许多令人兴奋的应用，这些应用利用水凝胶的多功能性用于颅面软组织工程。该领域最令人兴奋的发展之一是出现了先进的生物制造方法，可用于设计复杂的水凝胶系统，以促进组织的功能或结构修复。迄今为止，没有临床可用的基于水凝胶的治疗方法充分利用了当前的临床前进展。本综述调查了当前可用临床疗法的日益复杂的现状，并提出了一个框架，用于未来更广泛地使用水凝胶，着眼于可翻译性和美国对颅面应用的监管批准。
