Abstract：
Intra-articular (IA) platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) injections have shown efficacy and safety in treating osteoarthritis (OA). However, the effectiveness and mechanisms of combined intraosseous (IO) administration of these orthobiologics have yet to be explored.
The purpose of this study was to evaluate the effect on pain, cartilage, synovium/infrapatellar fat pad (IFP), and subchondral bone in rat knee OA, comparing isolated IA with combined IA and IO (IA+IO) injections of PRP or BMAC. It was hypothesized that combined injections would be superior to sole IA injections.
Controlled laboratory study.
A total of 48 rats were divided into 6 groups: sham (only joint puncture during OA induction with IA+IO saline injection treatment) and 5 groups with OA induction, control (IA+IO saline injection), PRP (IA PRP+IO saline injection), BMAC IA (IA BMAC+IO saline injection), PRP IA+IO (IA+IO PRP injection), and BMAC IA+IO (IA+IO BMAC injection). OA was induced by IA injection of monosodium iodoacetate (MIA). Rats were administered different orthobiologics according to their grouping 3 weeks after the MIA injection. Pain changes were evaluated using the weightbearing ratio assay at weeks 3, 4, 5, 7, and 9 after OA induction. Rats were euthanized at week 9 for gross, radiological, histological, immunohistochemical, and immunofluorescence assessments of cartilage, synovium, and subchondral bone.
Compared with the control group, all orthobiologics injection groups had reduced joint pain. Compared with IA injection, IA+IO injections provided superior pain relief by suppressing calcitonin gene-related peptide and substance P in both the synovium/IFP and subchondral bone. IA+IO injections slowed the progression of subchondral bone lesions by inhibiting CD31hiEmcnhi vessel formation and excessive osteoclast and osteoblast turnover while preserving subchondral bone microarchitecture, slowing cartilage degeneration. However, IA+IO injections did not outperform isolated IA injections in reducing synovitis and synovium/IFP fibrosis. Compared with PRP, BMAC exhibited superior inhibition of pain-related mediators, but no significant differences were observed in synovitis suppression, infrapatellar fat pad fibrosis, and subchondral bone protection.
IA+IO injections of orthobiologics were more effective in relieving pain, slowing cartilage degeneration, and inhibiting abnormal vascularization and remodeling compared with isolated IA injections. BMAC showed superior pain relief in the synovium/IFP and subchondral bone compared with PRP. Further research is needed to optimize PRP and BMAC components for enhanced efficacy in OA management.
Our findings contribute to advancing the understanding of pain relief mechanisms and support the endorsement of IO injection of orthobiologics for the treatment of OA and joint pain.
The purpose of this study was to evaluate the effect on pain, cartilage, synovium/infrapatellar fat pad (IFP), and subchondral bone in rat knee OA, comparing isolated IA with combined IA and IO (IA+IO) injections of PRP or BMAC. It was hypothesized that combined injections would be superior to sole IA injections.
Controlled laboratory study.
A total of 48 rats were divided into 6 groups: sham (only joint puncture during OA induction with IA+IO saline injection treatment) and 5 groups with OA induction, control (IA+IO saline injection), PRP (IA PRP+IO saline injection), BMAC IA (IA BMAC+IO saline injection), PRP IA+IO (IA+IO PRP injection), and BMAC IA+IO (IA+IO BMAC injection). OA was induced by IA injection of monosodium iodoacetate (MIA). Rats were administered different orthobiologics according to their grouping 3 weeks after the MIA injection. Pain changes were evaluated using the weightbearing ratio assay at weeks 3, 4, 5, 7, and 9 after OA induction. Rats were euthanized at week 9 for gross, radiological, histological, immunohistochemical, and immunofluorescence assessments of cartilage, synovium, and subchondral bone.
Compared with the control group, all orthobiologics injection groups had reduced joint pain. Compared with IA injection, IA+IO injections provided superior pain relief by suppressing calcitonin gene-related peptide and substance P in both the synovium/IFP and subchondral bone. IA+IO injections slowed the progression of subchondral bone lesions by inhibiting CD31hiEmcnhi vessel formation and excessive osteoclast and osteoblast turnover while preserving subchondral bone microarchitecture, slowing cartilage degeneration. However, IA+IO injections did not outperform isolated IA injections in reducing synovitis and synovium/IFP fibrosis. Compared with PRP, BMAC exhibited superior inhibition of pain-related mediators, but no significant differences were observed in synovitis suppression, infrapatellar fat pad fibrosis, and subchondral bone protection.
IA+IO injections of orthobiologics were more effective in relieving pain, slowing cartilage degeneration, and inhibiting abnormal vascularization and remodeling compared with isolated IA injections. BMAC showed superior pain relief in the synovium/IFP and subchondral bone compared with PRP. Further research is needed to optimize PRP and BMAC components for enhanced efficacy in OA management.
Our findings contribute to advancing the understanding of pain relief mechanisms and support the endorsement of IO injection of orthobiologics for the treatment of OA and joint pain.
摘要：
■关节内（IA）富血小板血浆（PRP）和骨髓穿刺液浓缩物（BMAC）注射已显示出治疗骨关节炎（OA）的功效和安全性。然而,这些直系生物制剂联合骨内(IO)给药的有效性和机制尚待探索.
■这项研究的目的是评估对疼痛的影响，软骨，滑膜/髌下脂肪垫（IFP），和大鼠膝关节OA的软骨下骨，比较分离的IA与组合的IA和IO(IA+IO)注射PRP或BMAC。假设联合注射将优于单独的IA注射。
■对照实验室研究。
■将48只大鼠分为6组:假手术组(IA+IO盐水注射治疗OA诱导时仅关节穿刺)和5组OA诱导组,对照（IA+IO盐水注射），PRP(IAPRP+IO生理盐水注射液),BMACIA（IABMAC+IO盐水注射），PRPIA+IO(IA+IOPRP注入),和BMACIA+IO（IA+IOBMAC注入）。OA是通过IA注射碘乙酸钠（MIA）诱导的。MIA注射后3周，根据分组给大鼠施用不同的直系生物制剂。在OA诱导后第3、4、5、7和9周，使用负重比测定法评估疼痛变化。在第9周对大鼠实施安乐死，放射学,组织学,免疫组织化学，和软骨的免疫荧光评估，滑膜,和软骨下骨.
■与对照组相比，所有直系生物制剂注射组均减轻了关节疼痛.与IA注射液相比，IAIO注射通过抑制滑膜/IFP和软骨下骨中的降钙素基因相关肽和P物质来提供优异的疼痛缓解。IA+IO注射通过抑制CD31hiEmcnhi血管形成和过度的破骨细胞和成骨细胞更新，同时保留软骨下骨微结构，减缓了软骨下骨病变的进展。减缓软骨退化。然而,IA+IO注射在减少滑膜炎和滑膜/IFP纤维化方面没有优于单独的IA注射。与PRP相比,BMAC对疼痛相关介质表现出优异的抑制作用，但在滑膜炎抑制方面没有观察到显著差异，髌下脂肪垫纤维化，和软骨下骨保护。
■IA+IO注射直系生物制剂更有效地缓解疼痛，减缓软骨退化，与单独的IA注射相比，抑制异常血管形成和重塑。与PRP相比，BMAC在滑膜/IFP和软骨下骨中显示出较好的疼痛缓解。需要进一步的研究来优化PRP和BMAC组件，以增强OA管理的功效。
■我们的发现有助于加深对疼痛缓解机制的理解，并支持IO注射直向生物制剂治疗OA和关节痛的认可。
■这项研究的目的是评估对疼痛的影响，软骨，滑膜/髌下脂肪垫（IFP），和大鼠膝关节OA的软骨下骨，比较分离的IA与组合的IA和IO(IA+IO)注射PRP或BMAC。假设联合注射将优于单独的IA注射。
■对照实验室研究。
■将48只大鼠分为6组:假手术组(IA+IO盐水注射治疗OA诱导时仅关节穿刺)和5组OA诱导组,对照（IA+IO盐水注射），PRP(IAPRP+IO生理盐水注射液),BMACIA（IABMAC+IO盐水注射），PRPIA+IO(IA+IOPRP注入),和BMACIA+IO（IA+IOBMAC注入）。OA是通过IA注射碘乙酸钠（MIA）诱导的。MIA注射后3周，根据分组给大鼠施用不同的直系生物制剂。在OA诱导后第3、4、5、7和9周，使用负重比测定法评估疼痛变化。在第9周对大鼠实施安乐死，放射学,组织学,免疫组织化学，和软骨的免疫荧光评估，滑膜,和软骨下骨.
■与对照组相比，所有直系生物制剂注射组均减轻了关节疼痛.与IA注射液相比，IAIO注射通过抑制滑膜/IFP和软骨下骨中的降钙素基因相关肽和P物质来提供优异的疼痛缓解。IA+IO注射通过抑制CD31hiEmcnhi血管形成和过度的破骨细胞和成骨细胞更新，同时保留软骨下骨微结构，减缓了软骨下骨病变的进展。减缓软骨退化。然而,IA+IO注射在减少滑膜炎和滑膜/IFP纤维化方面没有优于单独的IA注射。与PRP相比,BMAC对疼痛相关介质表现出优异的抑制作用，但在滑膜炎抑制方面没有观察到显著差异，髌下脂肪垫纤维化，和软骨下骨保护。
■IA+IO注射直系生物制剂更有效地缓解疼痛，减缓软骨退化，与单独的IA注射相比，抑制异常血管形成和重塑。与PRP相比，BMAC在滑膜/IFP和软骨下骨中显示出较好的疼痛缓解。需要进一步的研究来优化PRP和BMAC组件，以增强OA管理的功效。
■我们的发现有助于加深对疼痛缓解机制的理解，并支持IO注射直向生物制剂治疗OA和关节痛的认可。
