■肩袖修复后骨-肌腱界面(BTI)的功能恢复是一个挑战。因此,已经研究了许多用于促进BTI愈合的生物相容性生物材料。
■确定具有时空递送生长因子(GFs)的支架在肩袖修复后加速BTI愈合的功效。
■对照实验室研究。
■一种先进的三维打印技术用于制造具有时空递送多个靶向肌腱的GFs的生物活性支架,纤维软骨,和骨骼区域。总的来说,使用50只兔子:2只非手术对照和48只诱发慢性肩袖撕裂(RCT)的兔子。RCT动物分为3组:(A)注射生理盐水,(B)无GF的支架,和(C)具有GF的支架。为了诱导慢性模型,RCT未修复6周;然后,使用或不使用生物活性支架进行手术修复.对于B组和C组,每个支架植入在骨足印和冈上肌腱之间.修复四周后,我们进行了定量实时聚合酶链反应和免疫荧光分析,以评估再生愈合的早期迹象.组织学,生物力学,修复后12周进行显微计算机断层扫描分析。
■C组I型胶原α1、III型胶原α1和聚集蛋白聚糖的mRNA表达最高。免疫荧光分析显示,当用GFs支架修复时,在BTI处形成聚集蛋白聚糖/胶原蛋白II纤维软骨基质。组织学分析显示胶原纤维连续性更大,更致密的胶原纤维,与其他组相比,GF嵌入支架中的肌腱-骨接头更成熟。C组表现出最高的负载与故障率,和模量映射表明,用GF嵌入的支架修复的BTI的微观力学性能分布与天然BTI相当。显微计算机断层扫描分析确定了C组中最高的骨矿物质密度和骨体积/总体积比。
■具有空间嵌入GFs的生物活性支架具有促进兔模型中慢性RCT的BTI愈合的显着潜力。
■具有GF时空递送的支架可以用作现成的生物材料移植物,以促进RCT的愈合。
Functional restoration of the bone-to-tendon interface (BTI) after rotator cuff repair is a challenge. Therefore, numerous biocompatible biomaterials for promoting BTI healing have been investigated.
To determine the efficacy of scaffolds with spatiotemporal delivery of growth factors (GFs) to accelerate BTI healing after rotator cuff repair.
Controlled laboratory study.
An advanced 3-dimensional printing technique was used to fabricate bioactive scaffolds with spatiotemporal delivery of multiple GFs targeting the tendon, fibrocartilage, and bone regions. In total, 50 rabbits were used: 2 nonoperated controls and 48 rabbits with induced chronic rotator cuff tears (RCTs). The animals with RCTs were divided into 3 groups: (A) saline injection, (B) scaffold without GF, and (C) scaffold with GF. To induce chronic models, RCTs were left unrepaired for 6 weeks; then, surgical repairs with or without bioactive scaffolds were performed. For groups B and C, each scaffold was implanted between the bony footprint and the supraspinatus tendon. Four weeks after repair, quantitative real-time polymerase chain reaction and immunofluorescence analyses were performed to evaluate early signs of regenerative healing. Histological, biomechanical, and micro-computed tomography analyses were performed 12 weeks after repair.
Group C had the highest mRNA expression of collagen type I alpha 1, collagen type III alpha 1, and aggrecan. Immunofluorescence analysis showed the formation of an aggrecan+/collagen II+ fibrocartilaginous matrix at the BTI when repaired with scaffold with GFs. Histologic analysis revealed greater collagen fiber continuity, denser collagen fibers, and a more mature tendon-to-bone junction in GF-embedded scaffolds than those in the other groups. Group C demonstrated the highest load-to-failure ratio, and modulus mapping showed that the distribution of the micromechanical properties of the BTI repaired with GF-embedded scaffolds was comparable with that of the native BTI. Micro-computed tomography analysis identified the highest bone mineral density and bone volume/total volume ratio in group C.
Bioactive scaffolds with spatially embedded GFs have significant potential to promote the BTI healing of chronic RCTs in a rabbit model.
The scaffolds with spatiotemporal delivery of GF may serve as an off-the-shelf biomaterial graft to promote the healing of RCTs.