Trbojevic Sara, Taboas Juan M, Almarza Alejandro J
Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Tissue Eng Part A. 2025 Feb;31(3-4):126-138. doi: 10.1089/ten.tea.2024.0226. Epub 2024 Dec 26.
Long bone and craniofacial bone fractures amount to an overwhelming expenditure for patients and health care systems each year. Overall, 5-10% of all bone fractures result in some form of delayed or nonunion fractures. Nonunions occur from insufficient mechanical stabilization or a compromised wound environment lacking in vasculature and progenitor cells. The current standard for treating these critical-sized fractures and defects is the use of autologous bone grafts. However, advancements in tissue engineering have cultivated a shift in scientific efforts toward harnessing the body's own regenerative resources. As such, research on fracture healing has shifted as well. Transforming growth factor-beta 1 (TGFβ-1) has been studied in fracture healing for over 25 years, though many of these studies have been or in small animal models. The few studies in large animals have disagreement due to the heterogeneity within the experimental design. Because TGFβ-1 plays such a crucial role in the bone healing process, this systematic review investigates the application of TGFβ-1 in various carrier vehicles for repairing bone injuries in large animal and rabbit models. A systematic search was conducted in PubMed, Embase, and Web of Science (from database construction-October 2024). A total of 244 articles were screened, and 24 studies were included for review. Most large animal long bone studies used coated titanium implants, while most rabbit long bone studies used some form of degradable polymer constructs. TGFβ-1 doses in large animal long bone studies range from 0.005 to 750 µg, doses in large animal calvaria and mandible studies range from 1 to 5000 µg, and doses in rabbit long bone studies range from 0.05 to 120 µg. Nineteen out of 24 articles reviewed indicate successful use of TGFβ-1 for bone regeneration compared with experimental controls. It is clear that dose and controlled release of growth factor play a crucial role in defect closure, but outcome measures and success criteria were inconsistent across studies. More studies with consistent experimental designs are critical for understanding the therapeutic potential of TGFβ-1 in fracture repair, but overall, this review indicates that TGFβ-1 can be used alone or in conjunction with other growth factors to accelerate successful bone repair.
每年，长骨和颅面骨骨折给患者和医疗保健系统带来了巨大的支出。总体而言，所有骨折中有5%-10%会导致某种形式的延迟愈合或骨不连。骨不连是由于机械稳定性不足或伤口环境受损，缺乏血管和祖细胞所致。目前治疗这些临界尺寸骨折和缺损的标准方法是使用自体骨移植。然而，组织工程学的进展促使科学研究方向转向利用人体自身的再生资源。因此，骨折愈合的研究也发生了转变。转化生长因子-β1（TGFβ-1）在骨折愈合方面的研究已有25年之久，不过其中许多研究是在体外或小动物模型中进行的。在大型动物身上进行的少数研究由于实验设计的异质性而存在分歧。由于TGFβ-1在骨愈合过程中起着至关重要的作用，本系统评价研究了TGFβ-1在各种载体中用于修复大型动物和兔子模型骨损伤的应用情况。在PubMed、Embase和Web of Science（从数据库建立至2024年10月）中进行了系统检索。共筛选出244篇文章，纳入24项研究进行综述。大多数大型动物长骨研究使用涂覆钛植入物，而大多数兔子长骨研究使用某种形式的可降解聚合物构建体。大型动物长骨研究中TGFβ-1的剂量范围为0.005至750μg，大型动物颅骨和下颌骨研究中的剂量范围为1至5000μg，兔子长骨研究中的剂量范围为0.05至120μg。在纳入综述的24篇文章中，有19篇表明与实验对照组相比，TGFβ-1成功用于骨再生。显然，生长因子的剂量和控释在缺损闭合中起着关键作用，但各研究的结果测量和成功标准并不一致。开展更多实验设计一致的研究对于理解TGFβ-1在骨折修复中的治疗潜力至关重要，但总体而言，本综述表明TGFβ-1可单独使用或与其他生长因子联合使用，以加速骨修复的成功。
