1.1 本指南涵盖了 体内 评估旨在修复或再生骨骼的组织工程医疗产品（TEMP）。本指南中包含的TEMP可由天然或合成生物材料（生物相容和可生物降解）或其复合物组成，并可含有细胞或生物活性剂，如生长因子、合成肽、质粒或cDNA。本指南中描述的模型是节段性临界尺寸缺陷，根据定义，如果不进行治疗，这些缺陷将无法填充活组织。 因此，这些模型代表了对材料诱导或增强骨生长能力的严格测试。 1.2 指南包括各种动物模型的描述和原理，包括大鼠（鼠）、兔子（麻风）、狗（犬）、山羊（山羊）和绵羊（绵羊）。简要描述并参考了基于射线照相、组织学和力学分析的结果测量。用户应参考特定的测试方法以了解更多详细信息。 1.3 本指南不包括原材料测试、生物材料制备、灭菌或产品包装。 参考文件（第节）中提供了这些步骤的ASTM标准 2. ). 1.4 使用本指南中包含的任何方法可能不会产生与一个或多个特定应用中的临床表现一致的结果。 1.5 其他临床前方法也可能适用，本指南并不排除此类方法。材料必须适合其预期用途。这方面还需要进行额外的生物检测。 1.6 以国际单位制表示的值应视为标准值。 本标准不包括其他测量单位。 1.7 本标准并不旨在解决与其使用相关的所有安全问题（如有）。本标准的使用者有责任在使用前建立适当的安全、健康和环境实践，并确定监管限制的适用性。 1.8 本国际标准是根据世界贸易组织技术性贸易壁垒（TBT）委员会发布的《国际标准、指南和建议制定原则决定》中确立的国际公认标准化原则制定的。 =====意义和用途====== 4.1 本指南旨在提供一系列 体内 以帮助临床前研究和开发用于骨临床修复或再生的组织工程医疗产品（TEMP）。 4.2 本指南包括动物模型、手术注意事项、组织处理以及组织标本的定性和定量分析的描述。 4.3 建议用户使用适当的ASTM和其他指南对材料、TEMP或两者进行细胞毒性和生物相容性测试 体内 在此描述的模型。 4.4 建议安全测试符合美国食品和药物管理局《良好实验室规范条例》21 CFR 58的规定。 4.5 支持监管提交的安全性和有效性研究（例如，美国的研究器械豁免（IDE）、上市前批准（PMA）、510K、研究新药（IND）或生物制剂许可证申请（BLA）提交）应分别符合监管机构关于医疗器械、生物制剂或药物开发的适当指南。 4.6 动物模型结果不一定能预测人类的结果，因此，应谨慎解释其对人类条件的潜在适用性。

1.1 This guide covers general guidelines for the in vivo assessment of tissue-engineered medical products (TEMPs) intended to repair or regenerate bone. TEMPs included in this guide may be composed of natural or synthetic biomaterials (biocompatible and biodegradable) or composites thereof, and may contain cells or biologically active agents such as growth factors, synthetic peptides, plasmids, or cDNA. The models described in this guide are segmental critical size defects which, by definition, will not fill with viable tissue without treatment. Thus, these models represent a stringent test of a material’s ability to induce or augment bone growth. 1.2 Guidelines include a description and rationale of various animal models including rat (murine), rabbit (leporine), dog (canine), goat (caprine), and sheep (ovine). Outcome measures based on radiographic, histologic, and mechanical analyses are described briefly and referenced. The user should refer to specific test methods for additional detail. 1.3 This guide is not intended to include the testing of raw materials, preparation of biomaterials, sterilization, or packaging of the product. ASTM standards for these steps are available in the Referenced Documents (Section 2 ). 1.4 The use of any of the methods included in this guide may not produce a result that is consistent with clinical performance in one or more specific applications. 1.5 Other preclinical methods may also be appropriate and this guide is not meant to exclude such methods. The material must be suitable for its intended purpose. Additional biological testing in this regard would be required. 1.6 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard. 1.7 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use. 1.8 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee. ====== Significance And Use ====== 4.1 This guide is aimed at providing a range of in vivo models to aid in preclinical research and development of tissue-engineered medical products (TEMPs) intended for the clinical repair or regeneration of bone. 4.2 This guide includes a description of the animal models, surgical considerations, and tissue processing as well as the qualitative and quantitative analysis of tissue specimens. 4.3 The user is encouraged to use appropriate ASTM and other guidelines to conduct cytotoxicity and biocompatibility tests on materials, TEMPs, or both, prior to assessment of the in vivo models described herein. 4.4 It is recommended that safety testing be in accordance with the provisions of the FDA Good Laboratory Practices Regulations 21 CFR 58. 4.5 Safety and effectiveness studies to support regulatory submissions (for example, Investigational Device Exemption (IDE), Premarket Approval (PMA), 510K, Investigational New Drug (IND), or Biologics License Application (BLA) submissions in the U.S.) should conform to appropriate guidelines of the regulatory bodies for development of medical devices, biologics, or drugs, respectively. 4.6 Animal model outcomes are not necessarily predictive of human results and should, therefore, be interpreted cautiously with respect to potential applicability to human conditions.