Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits

The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(l-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. This study aims to 1) accelerate the rate of regeneration using the bioengineered ACL matrix by supplementation with bone marrow aspirate concentrate (BMAC) and growth factors (BMP-2, FGF-2, and FGF-8) and 2) increase matrix strength retention. Histological evaluation showed robust tissue regeneration in all groups. The presence of cuboidal cells reminiscent of ACL fibroblasts and chondrocytes surrounded by an extracellular matrix rich in anionic macromolecules was up-regulated in the BMAC group. This was not observed in previous studies and is indicative of enhanced regeneration. Additionally, intraarticular treatment with FGF-2 and FGF-8 was found to suppress joint inflammation. To increase matrix strength retention, we incorporated nondegradable fibers, polyethylene terephthalate (PET), into the PLLA bioengineered ACL matrix to fabricate a “tiger graft.” The tiger graft demonstrated the greatest peak loads among the experimental groups and the highest to date in a rabbit model. Moreover, the tiger graft showed superior osteointegration, making it an ideal bioengineered ACL matrix. The results of this study illustrate the beneficial effect bioactive factors and PET incorporation have on ACL regeneration and signal a promising step toward the clinical translation of a functional bioengineered ACL matrix.

The goal of developing a bioengineered anterior cruciate ligament (ACL) matrix is to provide an off-the-shelf product that is functionally superior to autografts and allografts currently used for ACL reconstruction surgeries. There is clear need for advancement in this area as 30% of young active patients reinjure their ACL after surgery (1). Furthermore, athletes in the National Basketball Association and National Football League have a return-to-sport time after ACL reconstruction of 11.6 and 10.8 mo, respectively (2, 3). This lengthy period of rehabilitation has spurred interest in bioengineered ACL matrices that can accelerate and enhance ACL regeneration, so that all patients can return to their preinjury performance level faster.Our group previously fabricated a poly(l-lactic) acid (PLLA) bioengineered ACL matrix and evaluated its performance in rabbit ACL reconstruction models (4–7). The bioengineered ACL matrix resulted in excellent tissue regeneration, while experiencing a 41 to 66% rupture rate in vivo (4, 5). The cause of these ruptures was likely due to the interplay between the rate of tissue regeneration and matrix fatigue. Thus, this study aims to 1) accelerate ACL regeneration by supplementing the bioengineered ACL matrix with bone marrow aspirate concentrate (BMAC) and growth factors (bone morphogenetic protein 2 [BMP-2], fibroblast growth factor 2 [FGF-2], and FGF-8); and 2) increase the strength retention of the bioengineered ACL matrix by incorporating nondegradable polyethylene terephthalate (PET) yarns.BMAC is a promising translational stem cell therapy as it can be harvested and applied during surgery and is not regulated by the US Food and Drug Administration (FDA) (8, 9). The ability of BMAC to enhance the repair of damaged rotator cuff (10) and meniscus (11) tissues has been demonstrated in rabbit models. Thus, we hypothesized that the application of BMAC would serve as a source of progenitor cells and bioactive factors that would accelerate ACL regeneration. This report evaluates the feasibility of obtaining BMAC in a rabbit ACL reconstruction model and its regenerative potential.Growth factors have been widely investigated to accelerate bone and ligament regeneration through the proliferation and differentiation of progenitor cells (12). FGFs have been shown to stimulate the proliferation of cells and enhance tissue healing. In particular, FGF-2 has been shown to accelerate ligament healing (13), and a member of the FGF-8 subfamily has been shown to stimulate cartilage healing in a clinical study (14). Furthermore, the synergistic application of FGF-2 and FGF-8 induced dedifferentiation of mature cells in axolotls (15). Given the evidence supporting the proregenerative qualities of FGF-2 and FGF-8, we chose to apply FGF-2 and FGF-8 simultaneously in the intraarticular space. We hypothesized that the combinatorial application of FGF-2 and FGF-8 would accelerate ligamentization of the bioengineered ACL matrix by promoting the proliferation of progenitor cells and dedifferentiation of mature cells in the synovial environment.To accelerate bone regeneration, we utilized bone morphogenetic protein 2 (BMP-2), which is approved by the US FDA for a range of lumbar spinal fusion procedures and has been shown in ACL reconstruction models to enhance osteointegration of tendon grafts (16–18). In our previous study, we demonstrated that BMP-2 saline injections could enhance osteoid seam width and reduce bone tunnel cross-sectional area, a sign of bone regeneration (5). However, the effect was limited, likely due to the lack of a drug carrier. In this study, we hypothesized that the addition of a drug delivery carrier, fibrin glue (19–22), would potentiate the effect of BMP-2 and promote bone formation (23).The first iteration of the bioengineered ACL matrix, termed the “L-C ligament,” was completely biodegradable and composed of only PLLA yarns (4). The high rupture rate found in our previous study motivated us to modify the material composition of the bioengineered ACL matrix to reduce its mechanical fatigue rate. A compelling polymer to reduce fatigue rate is PET, a biocompatible nondegradable polymer with high tensile strength that has previously been utilized for orthopedic applications (24). To date, no study has investigated the use of a composite PLLA and PET bioengineered ACL matrix for ACL reconstruction. Following the patented design by Laurencin and colleagues (25), a composite bioengineered ACL matrix, termed the “tiger graft,” composed of 20 PLLA yarns and 4 PET yarns, was fabricated. The PLLA facilitates a greater volume of tissue regeneration as it gradually degrades, while the PET bolsters the mechanical strength of the matrix during the early phases of healing. We hypothesized that the tiger graft would have increased mechanical strength retention over the implantation period.The overall goal of this study was to accelerate ACL regeneration of a bioengineered ACL matrix by supplementation with BMAC and growth factors (BMP-2, FGF-2, and FGF-8) and by modulating the material composition of the matrix (Fig. 1). We evaluated the ligamentization and osteointegration of the bioengineered ACL matrices histologically. Microcomputed tomography (µCT) was performed to evaluate bone tunnel regeneration. The inflammatory and remodeling state of the synovial fluid was evaluated using an enzyme-linked immunosorbent assay (ELISA). Finally, biomechanical testing was conducted to determine the strength retention of the bioengineered ACL matrices.Open in a separate windowFig. 1.Fabrication of the bioengineered ACL matrix and implantation in a rabbit ACL reconstruction model. (A) Depiction of the braiding machine used to fabricate the bioengineered ACL matrices and the resulting biphasic structure of the matrix. Each matrix was composed of 24 yarns. (B) For the L-C ligament, 24 yarns of PLLA were braided together. For the tiger graft, 20 yarns of PLLA and 4 yarns of PET were braided together. Experimental groups were evaluated at 12 wk, and the L-C ligament (control) was further evaluated at 24 wk. (C) View of implanted bioengineered ACL matrix at the time of surgery (Left) and the application of fibrin glue (Right). BMAC or growth factors were mixed with fibrin glue for the experimental groups. (D) Representative image demonstrating the implantation of a fibrin gel in the tibial bone tunnel (Left, blue arrow) and subsequent fixation of a titanium suture button (Right).     

体外冲击波联合海桐皮汤治疗中晚期肩周炎临床观察

目的:观察体外冲击波联合海桐皮汤外敷熏洗治疗中晚期肩周炎的临床疗效,为中晚期肩周炎的治疗提供一种更好的参考方案。方法:对纳入标准的患者60例采用随机数字法分为观察组和对照组,每组30例。观察组采用本院JDPN-VC型系列体外冲击波碎石机联合海桐皮汤外敷熏洗进行治疗,对照组采用本院JDPN-VC型系列体外冲击波碎石机单一治疗。以肩部疼痛评分和运动功能评分作为指标,对治疗后的效果进行评定。结果:治疗后观察组肩部疼痛评分、运动功能评分均明显改善(P0.05),观察组治疗总有效率明显高于对照组(P0.05)。观察过程中两组均无严重不良反应。结论:体外冲击波联合海桐皮汤外敷熏洗治疗中晚期肩周炎,疗程短,复发率低,临床上值得推广。     

“养筋汤”加味合盐酸氨基葡萄糖片口服治疗膝骨性关节炎28例

目的：观察“养筋汤”加味合盐酸氨基葡萄糖片口服治疗膝骨性关节炎的临床治疗疗效。方法：将56例膝骨性关节炎患者随机分为治疗组与对照组,治疗组28例采用“养筋汤加味”合盐酸氨基葡萄糖片口服治疗,对照组28例单纯采用盐酸氨基葡萄糖片口服治疗。结果：治疗组28例中,优秀18例,良好7例,无效3例,总优良率为89.2％;对照组28例中,优秀10例,良好8例,无效10例,总优良率为64.3％(P<0.05)。结论 “养筋汤”加味合盐酸氨基葡萄糖片口服治疗早期膝骨性关节炎临床效果较明显,临床上可供借鉴。     

同种异体肌腱修复手部肌腱缺损优良率的Meta分析

目的通过Meta分析统计同种异体肌腱用于手部肌腱缺损移植修复优良率。方法检索1966年~2015年间异体肌腱用于手部肌腱缺损移植修复的相关文献,采用循证医学Meta分析对患者手部肌腱移植修复优良率进行综合分析。结果使用随机效应模型计算单组率的Meta分析,同种异体肌腱移植优良率75%(69%~82%)。进一步分层分析,8篇使用手指数为样本量单位的研究移植优良率为75%(66~83%),11篇以病例数为样本量单位的研究移植优良率为76%(68%~85%)。结论同种异体肌腱用于手部肌腱缺损移植的优良率约为75%。     

Complications of hand surgery

Hand surgery involves the surgical treatment of hand conditions and encompasses small bone fixation, arthroscopy, joint replacement and reconstruction of tendon and nerves. Complications following surgery to the hand may be due to patient factors, surgical decisions and the complex anatomy of the hand. Here we describe the complications associated with common surgical interventions for both elective and traumatic injuries to the hand. Following hand surgery, a balance between immobilisation and early range of motion is offset by the risk of wound complications, non-union of fractures and tendon re-rupture with stiffness and reduced range of motion of the digits. Superficial infection is relatively common following procedures to the hand, however long-term sequelae are rare. Implant failure, subsidence, instability and reduced range of motion are seen following arthroplasty procedures. Complex regional pain syndrome offers a significant challenge following injury to the hand and specifically after surgical procedures. Surgeons should consider the risk of particular surgical techniques, other perioperative factors and patient factors that may contribute to the development of complications following hand surgery. Patients should be adequately counselled in order to make an informed decision regarding the management of their condition.     

腓骨长肌腱和腘绳肌腱重建前交叉韧带的系统评价

背景:近年报道,腓骨长肌腱可作为重建前交叉韧带新的移植材料,且能取得与腘绳肌腱同等效果,有必要对这2种重建前交叉韧带的移植材料进行系统评价。目的:采用Meta分析方法评价腓骨长肌腱和腘绳肌腱重建前交叉韧带的临床疗效。方法:采用中英文分别在中文数据库(万方医学、中国知网、维普医药、中国生物医学)、英文数据库(Ovid、Pub Med、Web of Science、Embase、Cochrane library)检索腓骨长肌腱和腘绳肌腱重建前交叉韧带的临床对照试验,检索时限从自建库至2019年3月,并由2名评价员通过筛选文献、文献评价、提取数据,并在Revman5.3软件进行Meta分析。结果与结论:(1)通过制定的检索式共检索出中英文文献413篇,最终符合纳入标准10篇,包括647例重建前交叉韧带患者,其中271例使用腓骨长肌腱重建,376例采用腘绳肌腱重建;(2)Meta分析显示:腓骨长肌腱组术后12个月的Lysholm评分、术后6个月的IKDC评分高于腘绳肌腱组(MD=1.23,95%CI[0.31,2.51],P=0.0009;MD=3.19,95%CI[0.07,6.31],P=0.02),术后并发症发生率低于腘绳肌腱组(OR=0.15,95%CI[0.03,0.69],P=0.01);两组术后6,12个月的Tegner评分、关节活动度、关节松弛程度,以及术后6个月的Lysholm评分、术后12个月的IKDC评分比较差异均无显著性意义(P> 0.05);(3)结果表明,腓骨长肌腱重建前交叉韧带的临床效果与腘绳肌腱相当,术后12个月的Lysholm评分、术后6个月的IKDC评分优于腘绳肌腱组,并且可减少术后并发症。临床上可推荐腓骨长肌腱代替腘绳肌腱重建前交叉韧带,但是纳入文献质量限制,需要更高级别的证据。     

Long-term outcome of superficialis-to-profundus tendon transfer in patients with clenched fist due to spastic hemiplegia

Background. Spastic hemiplegia is a common feature after stroke, which can result in a clenched fist deformity with secondary hygienic problems and pain. Operative treatment can improve these problems, although literature about its long-term effects is lacking.

Purpose. To determine whether Superficialis-to-Profundus tendon (StP-) transfer procedure leads to permanent improvement of hygiene and reduction of pain in patients with clenched fist due to spastic hemiplegia following stroke.

Method. Patients who underwent a StP-transfer in 2003 – 2005 were evaluated on skin condition, upper extremity joint mobility, resting position and muscle tone and with VAS scores on hygiene maintenance and pain in the hand.

Results. Six patients (mean age 54 years; duration after stroke 10 years) were included. Indications to operate were hygienic problems only (3) or combined with pain (3). The average follow-up period was 19 months. After 6 weeks of post-operative splinting, no standard follow-up was applied. Serious post-operative complications were not reported. At follow-up no hygienic problems were present and pain was decreased in all except one patient. All hands could passively be fully opened. In resting position, flexion was seen in the MCP-joints (60 – 90°). Muscle tone was raised in flexors of the wrist and fingers and m. adductor pollicis (Ashworth 1 – 2). Given the same pre- and post-operative circumstances, all patients would agree to have the surgery over again.

Conclusion. Even 19 months after the StP-transfer for clenched fist, all operated hands could still be fully opened and there was a permanent improvement of hygiene and pain reduction.     

胡连上清汤治疗咽喉口腔疾病的疗效观察

目的分析胡连上清汤治疗咽喉口腔疾病的疗效。方法选择2003年1月-2009年3月于我科就诊的咽喉口腔疾病患者108例，随机分为治疗组60例、对照组48例。治疗组胡连上清汤治疗，对照组西医治疗，比较两组患者疗效。结果治疗组总有效率93．30％，对照组总有效率77．08％。结论胡连上清汤治疗咽喉口腔疾病的疗效较佳，值得临床推广。