4. 两种植入材料在兔体内模型中的比较

IF 2.5 Q3 Medicine

North American Spine Society Journal Pub Date : 2025-07-01 DOI:10.1016/j.xnsj.2025.100698

Boyle C. Cheng PhD , Daniel T. Altman MD, FACS

{"title":"4. 两种植入材料在兔体内模型中的比较","authors":"Boyle C. Cheng PhD , Daniel T. Altman MD, FACS","doi":"10.1016/j.xnsj.2025.100698","DOIUrl":null,"url":null,"abstract":"<div><h3>BACKGROUND CONTEXT</h3><div>The study of the relationship between the musculoskeletal system and the immune system has become an increasingly important consideration in biomaterials research. Investigation of the immune response provides insight on the efficacy of current design materials in spinal implant devices and also offers a potential clinical understanding of complications. The potential for adverse events, including a fibrotic response, presents challenges that should be addressed. Studies involving the pro-inflammatory cytokine response inform on the mechanism of fibrous development pathway which has been reported with PEEK spinal interbody implants. With bone grafting materials, the probability of arthrodesis and bone apposition increases due to the selected materials. It is hypothesized that bone contact with PEEK devices would be different compared to titanium and the various surface finishes that can be applied.</div></div><div><h3>PURPOSE</h3><div>The purpose of this study was to compare the in vivo bone response to PEEK as an implant material compared to titanium with different surface roughness as an implant material. Specifically, microCT data was used to quantify new bone formation within the peri-prosthetic region, and histology was used to evaluate bone apposition and the presence of soft tissue at the bone-implant interface</div></div><div><h3>STUDY DESIGN/SETTING</h3><div>A rabbit distal femur model with two distinct material cohorts was conducted to investigate the immune response and bone growth surrounding PEEK dowels compared to titanium dowels.</div></div><div><h3>PATIENT SAMPLE</h3><div>N/A</div></div><div><h3>OUTCOME MEASURES</h3><div>N/A</div></div><div><h3>METHODS</h3><div>A rabbit distal femoral condyle bone defect model with two separate materials was conducted. PEEK and titanium dowels (4.5mm diameter x 8mm) with a central graft window were implanted into skeletally mature New Zealand White rabbits (3-4 kg). Implants did not contain graft material in the graft chamber and were randomized to either the left or right distal femoral condyle. Test subjects were randomized into either 4- or 8-week cohorts and histological or immunological analyses (4 subjects per cohort). Samples retrieved at necropsy were fixed, and radiographic imaging completed using a SkyScan 1172 desktop MicroCT (16 µm isotropic voxel size). All scans were reconstructed with a constant attenuation coefficient to enable comparison of bone mineral density and volume (CTAn, Bruker).</div></div><div><h3>RESULTS</h3><div>When observing inflammatory cytokine production, our ELISA data showed a significant decrease in TNFα and IL-1ß in PEEK implants. We also observed a difference in IL-1ß production from MSCs in culture titanium when compared to PEEK alone on Day 7, and a significant difference by Day 14. Mineralization data measured from microCT on harvested distal femurs of implanted rabbits was analyzed using a one-way ANOVA with multiple comparisons. Similarly, higher levels of mineralized bone were evident on the roughened titanium cohort for the layer closest to the implant surface. The 0-136 micron surface showed statistically increased new bone formation when compared to the PEEK cohort. Other titanium surfaces also demonstrated an increase in bone mineralization.</div></div><div><h3>CONCLUSIONS</h3><div>Biomedical implant development has traditionally been a strong area of research due to the ongoing necessity for immediate stabilization via fixation. The materials considered in device design should incorporate strong, durable, immunomodulatory material characteristics specifically for the acute condition following surgical procedures. PEEK has recently been developed and used in the field of orthopedics for both material and radiolucent properties. Although PEEK is a ubiquitous orthopedic spinal implant material, the inert, hydrophobic surface limits cell adhesion, attachment, and growth, which has the potential to lead to a persistent inflammatory response, fibrosis, and implant failure. The inclusion of traditional titanium implants has mitigated risks associated with the material evident in both the in vitro and short-term animal results. The bone mineralization immediately adjacent to the implant measured in microCT supports the layer at the bone-implant interface. The results suggest the use of titanium surfaces results in increased bone production, potentially leading to more bone apposition to the implant surface due to material and surface finish properties. The preliminary data suggest titanium implants could be advantageous for the suppression of early onset and a potentially sustained inflammatory response, and thus, resulting in bony on-growth with increased chances of arthrodesis.</div></div><div><h3>FDA Device/Drug Status</h3><div>This abstract does not discuss or include any applicable devices or drugs.</div></div>","PeriodicalId":34622,"journal":{"name":"North American Spine Society Journal","volume":"22 ","pages":"Article 100698"},"PeriodicalIF":2.5000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"4. A comparison of two implant materials in an in vivo rabbit model\",\"authors\":\"Boyle C. Cheng PhD , Daniel T. Altman MD, FACS\",\"doi\":\"10.1016/j.xnsj.2025.100698\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>BACKGROUND CONTEXT</h3><div>The study of the relationship between the musculoskeletal system and the immune system has become an increasingly important consideration in biomaterials research. Investigation of the immune response provides insight on the efficacy of current design materials in spinal implant devices and also offers a potential clinical understanding of complications. The potential for adverse events, including a fibrotic response, presents challenges that should be addressed. Studies involving the pro-inflammatory cytokine response inform on the mechanism of fibrous development pathway which has been reported with PEEK spinal interbody implants. With bone grafting materials, the probability of arthrodesis and bone apposition increases due to the selected materials. It is hypothesized that bone contact with PEEK devices would be different compared to titanium and the various surface finishes that can be applied.</div></div><div><h3>PURPOSE</h3><div>The purpose of this study was to compare the in vivo bone response to PEEK as an implant material compared to titanium with different surface roughness as an implant material. Specifically, microCT data was used to quantify new bone formation within the peri-prosthetic region, and histology was used to evaluate bone apposition and the presence of soft tissue at the bone-implant interface</div></div><div><h3>STUDY DESIGN/SETTING</h3><div>A rabbit distal femur model with two distinct material cohorts was conducted to investigate the immune response and bone growth surrounding PEEK dowels compared to titanium dowels.</div></div><div><h3>PATIENT SAMPLE</h3><div>N/A</div></div><div><h3>OUTCOME MEASURES</h3><div>N/A</div></div><div><h3>METHODS</h3><div>A rabbit distal femoral condyle bone defect model with two separate materials was conducted. PEEK and titanium dowels (4.5mm diameter x 8mm) with a central graft window were implanted into skeletally mature New Zealand White rabbits (3-4 kg). Implants did not contain graft material in the graft chamber and were randomized to either the left or right distal femoral condyle. Test subjects were randomized into either 4- or 8-week cohorts and histological or immunological analyses (4 subjects per cohort). Samples retrieved at necropsy were fixed, and radiographic imaging completed using a SkyScan 1172 desktop MicroCT (16 µm isotropic voxel size). All scans were reconstructed with a constant attenuation coefficient to enable comparison of bone mineral density and volume (CTAn, Bruker).</div></div><div><h3>RESULTS</h3><div>When observing inflammatory cytokine production, our ELISA data showed a significant decrease in TNFα and IL-1ß in PEEK implants. We also observed a difference in IL-1ß production from MSCs in culture titanium when compared to PEEK alone on Day 7, and a significant difference by Day 14. Mineralization data measured from microCT on harvested distal femurs of implanted rabbits was analyzed using a one-way ANOVA with multiple comparisons. Similarly, higher levels of mineralized bone were evident on the roughened titanium cohort for the layer closest to the implant surface. The 0-136 micron surface showed statistically increased new bone formation when compared to the PEEK cohort. Other titanium surfaces also demonstrated an increase in bone mineralization.</div></div><div><h3>CONCLUSIONS</h3><div>Biomedical implant development has traditionally been a strong area of research due to the ongoing necessity for immediate stabilization via fixation. The materials considered in device design should incorporate strong, durable, immunomodulatory material characteristics specifically for the acute condition following surgical procedures. PEEK has recently been developed and used in the field of orthopedics for both material and radiolucent properties. Although PEEK is a ubiquitous orthopedic spinal implant material, the inert, hydrophobic surface limits cell adhesion, attachment, and growth, which has the potential to lead to a persistent inflammatory response, fibrosis, and implant failure. The inclusion of traditional titanium implants has mitigated risks associated with the material evident in both the in vitro and short-term animal results. The bone mineralization immediately adjacent to the implant measured in microCT supports the layer at the bone-implant interface. The results suggest the use of titanium surfaces results in increased bone production, potentially leading to more bone apposition to the implant surface due to material and surface finish properties. The preliminary data suggest titanium implants could be advantageous for the suppression of early onset and a potentially sustained inflammatory response, and thus, resulting in bony on-growth with increased chances of arthrodesis.</div></div><div><h3>FDA Device/Drug Status</h3><div>This abstract does not discuss or include any applicable devices or drugs.</div></div>\",\"PeriodicalId\":34622,\"journal\":{\"name\":\"North American Spine Society Journal\",\"volume\":\"22 \",\"pages\":\"Article 100698\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"North American Spine Society Journal\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666548425001180\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"North American Spine Society Journal","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666548425001180","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

摘要

研究肌肉骨骼系统与免疫系统之间的关系已成为生物材料研究中越来越重要的考虑因素。对免疫反应的研究提供了对当前设计材料在脊柱植入装置中的功效的见解，也提供了对并发症的潜在临床理解。潜在的不良事件，包括纤维化反应，提出了应该解决的挑战。涉及促炎细胞因子反应的研究揭示了纤维发育途径的机制，该途径已被报道用于PEEK脊柱体间植入物。对于植骨材料，由于材料的选择，关节融合术和骨移位的可能性增加。据推测，与钛和各种表面处理相比，PEEK设备与骨骼的接触会有所不同。目的本研究的目的是比较PEEK作为种植材料与不同表面粗糙度的钛作为种植材料在体内的骨反应。具体来说，微ct数据被用来量化假体周围区域的新骨形成，组织学被用来评估骨的附着和骨-种植体界面处软组织的存在。研究设计/设置了一个具有两个不同材料队列的兔股骨远端模型，以研究与钛钉相比，PEEK钉周围的免疫反应和骨生长。采用两种不同材料建立兔股骨远端髁骨缺损模型。将PEEK和钛榫（直径4.5mm x 8mm）与中心移植窗植入骨骼成熟的新西兰大白兔（3-4 kg）体内。植入物在移植物腔内不含移植物材料，随机选择左或右股骨远端髁。试验对象被随机分为4周或8周的队列，并进行组织学或免疫学分析（每个队列4名受试者）。将尸检标本固定，并使用SkyScan 1172台式MicroCT（16µm各向同性体素尺寸）完成放射成像。所有扫描用恒定衰减系数重建，以便比较骨矿物质密度和体积（CTAn, Bruker）。结果在观察炎症细胞因子的产生时，我们的ELISA数据显示PEEK植入物中TNFα和IL-1ß的含量显著降低。我们还观察到，与单独使用PEEK相比，培养钛的MSCs在第7天产生IL-1ß的差异，到第14天差异显著。显微ct测量的矿化数据在移植兔的远端股骨上采集，使用多重比较的单因素方差分析。同样，在最接近种植体表面的粗糙钛组中，矿化骨的水平较高。与PEEK队列相比，0-136微米的表面在统计学上增加了新骨的形成。其他钛表面也显示出骨矿化的增加。生物医学种植体的发展一直是研究的热点领域，因为需要通过固定进行即刻稳定。在器械设计中考虑的材料应包括坚固、耐用、免疫调节材料特性，特别是针对外科手术后的急性状况。PEEK由于其材料和透光性，最近在骨科领域得到了发展和应用。虽然PEEK是一种普遍存在的骨科脊柱植入材料，但其惰性、疏水性表面限制了细胞的粘附、附着和生长，这有可能导致持续的炎症反应、纤维化和植入失败。传统的钛植入物降低了与材料相关的风险，这些风险在体外和短期动物实验结果中都很明显。在微ct测量中，紧邻种植体的骨矿化支持骨-种植体界面层。结果表明，钛表面的使用导致骨产量增加，由于材料和表面光洁度的特性，可能导致更多的骨与种植体表面相对立。初步数据表明，钛植入物可能有利于抑制早期发病和潜在的持续炎症反应，因此，导致骨生长增加关节融合术的机会。FDA器械/药物状态本摘要不讨论或包括任何适用的器械或药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

4. A comparison of two implant materials in an in vivo rabbit model

BACKGROUND CONTEXT

The study of the relationship between the musculoskeletal system and the immune system has become an increasingly important consideration in biomaterials research. Investigation of the immune response provides insight on the efficacy of current design materials in spinal implant devices and also offers a potential clinical understanding of complications. The potential for adverse events, including a fibrotic response, presents challenges that should be addressed. Studies involving the pro-inflammatory cytokine response inform on the mechanism of fibrous development pathway which has been reported with PEEK spinal interbody implants. With bone grafting materials, the probability of arthrodesis and bone apposition increases due to the selected materials. It is hypothesized that bone contact with PEEK devices would be different compared to titanium and the various surface finishes that can be applied.

PURPOSE

The purpose of this study was to compare the in vivo bone response to PEEK as an implant material compared to titanium with different surface roughness as an implant material. Specifically, microCT data was used to quantify new bone formation within the peri-prosthetic region, and histology was used to evaluate bone apposition and the presence of soft tissue at the bone-implant interface

STUDY DESIGN/SETTING

A rabbit distal femur model with two distinct material cohorts was conducted to investigate the immune response and bone growth surrounding PEEK dowels compared to titanium dowels.

PATIENT SAMPLE

N/A

OUTCOME MEASURES

N/A

METHODS

A rabbit distal femoral condyle bone defect model with two separate materials was conducted. PEEK and titanium dowels (4.5mm diameter x 8mm) with a central graft window were implanted into skeletally mature New Zealand White rabbits (3-4 kg). Implants did not contain graft material in the graft chamber and were randomized to either the left or right distal femoral condyle. Test subjects were randomized into either 4- or 8-week cohorts and histological or immunological analyses (4 subjects per cohort). Samples retrieved at necropsy were fixed, and radiographic imaging completed using a SkyScan 1172 desktop MicroCT (16 µm isotropic voxel size). All scans were reconstructed with a constant attenuation coefficient to enable comparison of bone mineral density and volume (CTAn, Bruker).

RESULTS

When observing inflammatory cytokine production, our ELISA data showed a significant decrease in TNFα and IL-1ß in PEEK implants. We also observed a difference in IL-1ß production from MSCs in culture titanium when compared to PEEK alone on Day 7, and a significant difference by Day 14. Mineralization data measured from microCT on harvested distal femurs of implanted rabbits was analyzed using a one-way ANOVA with multiple comparisons. Similarly, higher levels of mineralized bone were evident on the roughened titanium cohort for the layer closest to the implant surface. The 0-136 micron surface showed statistically increased new bone formation when compared to the PEEK cohort. Other titanium surfaces also demonstrated an increase in bone mineralization.

CONCLUSIONS

Biomedical implant development has traditionally been a strong area of research due to the ongoing necessity for immediate stabilization via fixation. The materials considered in device design should incorporate strong, durable, immunomodulatory material characteristics specifically for the acute condition following surgical procedures. PEEK has recently been developed and used in the field of orthopedics for both material and radiolucent properties. Although PEEK is a ubiquitous orthopedic spinal implant material, the inert, hydrophobic surface limits cell adhesion, attachment, and growth, which has the potential to lead to a persistent inflammatory response, fibrosis, and implant failure. The inclusion of traditional titanium implants has mitigated risks associated with the material evident in both the in vitro and short-term animal results. The bone mineralization immediately adjacent to the implant measured in microCT supports the layer at the bone-implant interface. The results suggest the use of titanium surfaces results in increased bone production, potentially leading to more bone apposition to the implant surface due to material and surface finish properties. The preliminary data suggest titanium implants could be advantageous for the suppression of early onset and a potentially sustained inflammatory response, and thus, resulting in bony on-growth with increased chances of arthrodesis.