UNASSIGNED: To explore the effect of chitosan (CS) hydrogel loaded with tendon-derived stem cells (TDSCs; hereinafter referred to as TDSCs/CS hydrogel) on tendon-to-bone healing after rotator cuff repair in rabbits.
UNASSIGNED: TDSCs were isolated from the rotator cuff tissue of 3 adult New Zealand white rabbits by Henderson step-by-step enzymatic digestion method and identified by multidirectional differentiation and flow cytometry. The 3rd generation TDSCs were encapsulated in CS to construct TDSCs/CS hydrogel. The cell counting kit 8 (CCK-8) assay was used to detect the proliferation of TDSCs in the hydrogel after 1-5 days of culture in vitro, and cell compatibility of TDSCs/CS hydrogel was evaluated by using TDSCs alone as control. Another 36 adult New Zealand white rabbits were randomly divided into 3 groups ( n=12): rotator cuff repair group (control group), rotator cuff repair+CS hydrogel injection group (CS group), and rotator cuff repair+TDSCs/CS hydrogel injection group (TDSCs/CS group). After establishing the rotator cuff repair models, the corresponding hydrogel was injected into the tendon-to-bone interface in the CS group and TDSCs/CS group, and no other treatment was performed in the control group. The general condition of the animals was observed after operation. At 4 and 8 weeks, real-time quantitative PCR (qPCR) was used to detect the relative expressions of tendon forming related genes (tenomodulin, scleraxis), chondrogenesis related genes (aggrecan, sex determining region Y-related high mobility group-box gene 9), and osteogenesis related genes (alkaline phosphatase, Runt-related transcription factor 2) at the tendon-to-bone interface. At 8 weeks, HE and Masson staining were used to observe the histological changes, and the biomechanical test was used to evaluate the ultimate load and the failure site of the repaired rotator cuff to evaluate the tendon-to-bone healing and biomechanical properties.
UNASSIGNED: CCK-8 assay showed that the CS hydrogel could promote the proliferation of TDSCs ( P<0.05). qPCR results showed that the expressions of tendon-to-bone interface related genes were significantly higher in the TDSCs/CS group than in the CS group and control group at 4 and 8 weeks after operation ( P<0.05). Moreover, the expressions of tendon-to-bone interface related genes at 8 weeks after operation were significantly higher than those at 4 weeks after operation in the TDSCs/CS group ( P<0.05). Histological staining showed the clear cartilage tissue and dense and orderly collagen formation at the tendon-to-bone interface in the TDSCs/CS group. The results of semi-quantitative analysis showed that compared with the control group, the number of cells, the proportion of collagen fiber orientation, and the histological score in the TDSCs/CS group increased, the vascularity decreased, showing significant differences ( P<0.05); compared with the CS group, the proportion of collagen fiber orientation and the histological score in the TDSCs/CS group significantly increased ( P<0.05), while there was no significant difference in the number of cells and vascularity ( P>0.05). All samples in biomechanical testing failed at the repair site during the testing process. The ultimate load of the TDSCs/CS group was significantly higher than that of the control group ( P<0.05), but there was no significant difference compared to the CS group ( P>0.05).
UNASSIGNED: TDSCs/CS hydrogel can induce cartilage regeneration to promote rotator cuff tendon-to-bone healing.
UNASSIGNED: 探讨以壳聚糖（chitosan，CS）负载肌腱干细胞（tendon-derived stem cells，TDSCs）构建的可注射型水凝胶（以下简称TDSCs/CS水凝胶）促进兔肩袖腱-骨愈合的效果。.
UNASSIGNED: 取3只成年新西兰大白兔肩袖组织，采用Henderson分步酶消化法分离培养TDSCs，并经多向分化及流式细胞术鉴定。以CS包裹第3代TDSCs构建TDSCs/CS水凝胶，体外培养1～5 d以细胞计数试剂盒8（cell counting kit 8，CCK-8）法检测水凝胶中TDSCs增殖情况，并以单纯TDSCs作为对照，评估TDSCs/CS水凝胶细胞相容性。另取36只成年新西兰大白兔，随机分为3组（ n=12），分别为肩袖修复组（对照组）、肩袖修复+CS水凝胶注射组（CS组）、肩袖修复+DSCs/CS水凝胶注射组（TDSCs/CS组）。3组建立肩袖损伤+单排技术修复模型后，CS组及TDSCs/CS组将对应水凝胶注入腱-骨界面处修复肩袖，对照组不作其他处理。术后观察动物一般情况，于4、8周取材，实时定量PCR（real-time quantitative PCR，qPCR）检测腱-骨界面成肌腱相关基因（腱调蛋白、转录因子），成软骨相关基因（蛋白聚糖、性别决定区Y框蛋白9），成骨相关基因（ALP、人Runt相关转录因子2）表达；另于8周取材行HE、Masson染色观察并行组织学半定量评分，生物力学测试修复肩袖极限载荷和失效部位，评价组织愈合情况和生物力学特性改变。.
UNASSIGNED: CCK-8法检测示共培养后CS水凝胶可促进TDSCs增殖（ P<0.05）。术后各组动物均存活至实验完成。术后4、8周，TSDCs/CS组的成肌腱、成软骨、成骨相关基因相对表达量均高于CS组和对照组（ P<0.05），TSDCs/CS组组内术后8周上述基因相对表达量亦高于术后4周（ P<0.05）。组织学染色示TDSCs/CS组腱-骨界面处有清晰的软骨组织和致密有序胶原形成，半定量分析结果示TDSCs/CS组与对照组相比，细胞数量、胶原纤维分布以及组织学评分增高（ P<0.05），血管数量降低（ P<0.05）；TDSCs/CS组与CS组相比，胶原纤维分布以及组织学评分均增高（ P<0.05），而细胞数量、血管数量差异无统计学意义（ P>0.05）。生物力学检测示所有样本测试过程中均在修复部位失效，TDSCs/CS组极限载荷高于对照组（ P<0.05），但与CS组比较差异无统计学意义（ P>0.05）。.
UNASSIGNED: TDSCs/CS水凝胶可以诱导兔肩袖肌腱和骨之间的软骨再生，促进腱-骨愈合。.

Knotted suture bridge repair (KSBR) has been widely proven to be an effective method for rotator cuff repairs. However, the occurrence of type 2 failure after suture bridge repair remains a frequent problem because of the stress concentration and disturbance of tendon perfusion in the medial row. The authors have developed the H-loop knotless double-row repair (HLDR) to counteract these problems.
To compare the biomechanical and histological outcomes of HLDR and KSBR for rotator cuff tear in the rabbit model.
Controlled laboratory study.
Acute bilateral supraspinatus tears were created on the shoulders of 46 New Zealand White rabbits. HLDR and KSBR were randomly performed on the left side or right side. Thirteen animals each were sacrificed at 2, 4, and 8 weeks after surgery (n = 39), with 6 rabbits used for histological evaluation and the other 7 rabbits for biomechanical testing. The remaining 7 animals from the original 46 were only used for initial biomechanical evaluation at week 0.
Macroscopically, all repaired tendons were connected to their footprint on the greater tuberosity without postoperative complications at 8 weeks after surgery. The HLDR group had significantly better histological bone-to-tendon integration compared with the KSBR group in terms of fibrocartilage regeneration, collagen composition, and fiber organization. The biomechanical outcomes in the HLDR group were demonstrated to be better than those of the KSBR group at time 0 and 8 weeks after surgery.
Both repair techniques were effective for rotator cuff tears in a rabbit rotator cuff tear model; however, HLDR demonstrated more advantages in improving biomechanical properties and histological tendon-to-bone healing compared with KSBR.
This animal study suggested that HLDR might be an alternative choice for rotator cuff tears in humans to increase tendon-to-bone healing and reduce the rate of failure to heal.

The availability of non-invasive means to evaluate and monitor tendon-bone healing processes in-vivo is limited. Micro Positron-Emission-Tomography (µPET) using 18F-Fluoride is a minimally invasive imaging modality, with which osteoblast activity and bone turnover can be assessed. The aim of this study was to investigate the use of serial in-vivo µPET/CT scans to evaluate bone turnover along the graft-tunnel interface in a rat ACL (anterior cruciate ligament) reconstruction model.
Unilateral autograft ACL reconstruction was performed in six rats. µPET/CT-scans using 18F-Fluoride were performed 7, 14, 21, and 28 days postoperatively. Standard uptake values (SUV) were calculated for three tunnel regions (intraarticular aperture (IAA), mid-tunnel, and extraarticular aperture (EAA)) of the proximal tibia. Animals were sacrificed at 28 days and evaluated with µCT and histological analysis.
SUVs in both bone tunnels showed an increased 18F-Fluoride uptake at 7 days when compared to 14, 21, and 28 days. SUVs showed a gradient on the tibial side, with most bone turnover in the IAA and least in the EAA. At 7, 14, 21, and 28 days, there were significantly higher SUV values in the IAA compared to the EAA (p = .01, < .01, < .01, < .01). SUVs positively correlated with new bone volumetric density obtained with μCT (r = 0.449, p = .013). Volumetric density of newly formed bone detected on μCT correlated with osteoblast numbers observed along the tunnels in histological sections (r = 0.452, p < .016).
Serial in-vivo µPET/CT-scanning has the potential to provide insight into bone turnover and therefore osteoblastic activity during the healing process. As a result, it allows us to directly measure the effect of interventional strategies in tendon-bone healing.

UNASSIGNED: There is growing interest in various biological supplements to improve tendon healing in patients after arthroscopic rotator cuff repair. The ideal biological supplement to strengthen rotator cuff remains unknown.
UNASSIGNED: To assess the safety and efficacy of autologous cultured dermal fibroblast (ADF) injection on tendon-to-bone healing in patients after arthroscopic rotator cuff repair.
UNASSIGNED: Case series; Level of evidence, 4.
UNASSIGNED: Included were 6 patients who underwent arthroscopic rotator cuff repair between June 2018 and March 2020; all patients had a full-thickness rotator cuff tear (>2 cm) involving the supraspinatus and infraspinatus tendons. The patients were injected with ADF between the repaired tendon and footprint during arthroscopic rotator cuff repair using the suture bridge technique. The safety of ADFs and the procedure was evaluated at 5 weeks postoperatively, and the anatomical healing of the repaired tendon was accessed at 6 months postoperatively using magnetic resonance imaging and at 12 months using ultrasonography. Outcomes including shoulder range of motion (ROM), visual analog scale (VAS) for pain, and functional scores were measured at 6 and 12 months postoperatively.
UNASSIGNED: Adverse reactions to ADF injection were not observed at 6 months after surgery. VAS and functional scores at 6 and 12 months postoperatively were significantly improved compared with preoperative scores (all P < .05). However, there was no significant difference on any ROM variable between preoperative and postoperative measurements at 6 and 12 months (all P > .05). No healing failure was found at 6 and 12 months postoperatively.
UNASSIGNED: There was no adverse reaction to ADF injection, and all patients had successful healing after rotator cuff repair. A simple and easily accessible ADF injection may be a novel treatment option for increasing the healing capacity of torn rotator cuff tendons. Further clinical research is needed to verify the study results.

BACKGROUND: The high failure rate of rotator cuff repairs requires the development of methods to enhance healing at the tendon-bone junction of the repair site.
OBJECTIVE: To assess functional recovery and structural outcomes in detail after implanting recombinant human bone morphogenetic protein-12 (rhBMP-12)/absorbable collagen sponge (ACS) as adjuvant treatment during open rotator cuff repair in patients over a 1-year postoperative follow-up.
METHODS: Randomized controlled trial; Level of evidence, 2.
METHODS: A total of 20 patients were randomized into 2 groups, rhBMP-12/ACS and standard-of-care (SOC) control, with 16 and 4 patients, respectively. The patients underwent open repair of a rotator cuff tear at least 2 to 4 cm wide; in the rhBMP-12/ACS group, this was augmented with a bioscaffold containing rhBMP-12. Follow-up assessments were conducted with a 100-mm visual analog scale (VAS) for pain and active and passive ranges of motion (ROMs) including forward flexion, elevation in the scapular plane, abduction, and external rotation at 12, 16, 26, 39, and 52 weeks after surgery; isometric strength in scapular abduction and external rotation at 16, 26, 39, and 52 weeks; and magnetic resonance imaging (MRI) at 12 and 52 weeks.
RESULTS: The mean VAS score decreased from 37.9 mm preoperatively to 13.8 mm at week 52, and ROM and isometric strength recovered at week 52 in the rhBMP-12/ACS group. The mean VAS score decreased from 48.3 mm preoperatively to 1.5 mm at week 52, and ROM (excluding external rotation) and isometric strength recovered by week 52 in the SOC control group. Of the 16 patients in the rhBMP-12/ACS group, 14 showed an intact repair at week 12; the MRI scans of the other 2 patients could not be evaluated because of artifacts. In the SOC control group, 1 patient showed repair failure. At week 52, 14 repairs in the rhBMP-12/ACS group and 2 repairs with available MRI scans in the SOC control group remained intact.
CONCLUSIONS: Functional recovery and structural outcomes in patients in whom rhBMP-12/ACS was used as adjuvant therapy in rotator cuff repair justify conducting future, larger, multicenter, prospective studies.
UNASSIGNED: NCT00936559, NCT01122498 (ClinicalTrials.gov identifier).

BACKGROUND: Rotator cuff repair is a common method to treat rotator cuff tears; however, retear rates remain high. High-frequency, low-magnitude vibration has been demonstrated to promote new bone formation in both animal models and in humans.
OBJECTIVE: This type of mechanical stimulation applied postoperatively will enhance tendon-to-bone healing and reduce postoperative retear rates.
METHODS: Randomized controlled trial; Level of evidence, 1.
METHODS: A randomized, double-blinded, placebo-controlled clinical trial was conducted to investigate the effects of 5 minutes of 80-Hz vibration applied daily after arthroscopic rotator cuff repair for 6 months on postoperative rotator cuff healing. The primary outcome was ultrasound-assessed repair integrity at 6 months after repair. Recruited patients were randomized into 2 groups: one group received a vibration device that oscillated at 80 Hz, and the other group received a placebo device.
RESULTS: The postoperative retear rates of both groups were similar (9.1% [5/55] in the vibration group, and 9.3% [5/54] in the placebo group) at 6 months as determined by ultrasound imaging. Vibration did provide acute pain relief at 6 weeks after surgery (visual analog scale [VAS] score, 2.24 ± 0.29 cm) compared with placebo (VAS score, 3.67 ± 0.48 cm) (P < .003). Six months after surgery, both groups had significant reductions in pain during overhead activities, at rest, and during sleep and overall shoulder pain compared with before surgery (P < .001). Both the vibration and placebo groups had significant increases in shoulder strength with abduction in the scapular plane, adduction, liftoff, internal rotation, and external rotation 6 months after surgery. Statistical analysis showed that vibration was not a contributing factor at improving these parameters in these periods.
CONCLUSIONS: High-frequency, low-magnitude vibration did provide acute pain relief on application 6 weeks after arthroscopic rotator cuff repair surgery. However, vibration did not improve tendon-to-bone healing, shoulder range of motion, shoulder strength, or shoulder pain with activities, at rest, and at night when compared with placebo.

Tendons and ligaments attach to bone through a transitional connective tissue with complex biomechanical properties. This unique tissue is not regenerated during healing, and surgical reattachment therefore often fails. The present study was designed to evaluate tendon healing in a bone tunnel and to evaluate the utilized rat model. Wistar rats (n = 61) were operated with the Achilles tendon through a bone tunnel in the distal tibia. Healing was evaluated at 2, 3, 4, and 12 weeks by biomechanical testing, bone mineral density and histology. After 2 weeks median (interquartile range) pull-out force was 2.2 N (1.9). The pull-out force increased chronologically, by 12 weeks fivefold to 11.2 N (11.4). Energy absorption, stiffness, and bone mineral density increased similarly. The histological analyses showed inflammation at early stages with increasing callus by time. Our data showed a slow healing response the first 4 weeks followed by an accelerated healing period, favoring that most of the gain in mechanical strength occurred later than 4 weeks postoperatively. These findings support the concern of a vulnerable tendon bone tunnel interface in the early stages of healing.

BACKGROUND: after anterior cruciate ligament (ACL) reconstruction, it is necessary to integrate free tendon graft biologically to the bone. In the present study, to verify whether a structure identical to the normal ligament-bone insertion could be regenerated at the tendon-bone interface without bone tunnel, we designed ACL reconstruction model without a tibial bone tunnel. Moreover, to enhance the integration process in this model, bone marrow-derived mesenchymal stem cells (bMSCs) were transplanted, and histological changes investigated. Our first hypothesis was that the grafted tendon would be anchored at part of the tendon-bone interface even if a bone tunnel was not created. Second hypothesis was that application of bMSCs at the tendon-bone interface would yield results histologically superior to those in controls.
METHODS: bilateral ACL reconstruction using our originally designed method was performed. Autologous bMSCs with the carrier were transplanted between the bottom of the grafted tendon and the bone pit of the tibia in the experimental limb, whereas the control limb received the carrier only. At 4 and 8 weeks after the operation, histological comparison between bMSCs and the control group was carried out.
CONCLUSIONS: even in our present ACL reconstruction model without a tibial bone tunnel, integration via chondroid tissue was seen at part of the tendon-bone interface. However, there were no appreciable differences between the groups. In ACL reconstruction, to enhance the tendon-bone integration without a bone tunnel would lead to save the graft length and prevent from bone tunnel complications (ex. Bone-tunnel enlargement after surgery).