Resection arthrodesis using distraction osteogenesis then plating as a hybrid surgical technique for the management of bone sarcomas of the distal tibia.

PURPOSE: We report the oncological and functional results of limb salvage for bone sarcomas involving the distal tibia using hybrid surgical technique of resection arthrodesis by bone transport then plating. METHODS: Five patients (mean age 18.6 years) with primary distal tibial sarcomas (two Ewing's sarcomas and three osteosarcomas) were treated by this method. The average duration of follow-up is 53 months. All patients accepted distraction osteogenesis with a standard technique using external fixator after wide (four cases) or marginal (one case) resection in the first operation. They were re-admitted for the second surgical treatment (plate insertion and removal of the external fixator) one to two months after they achieved the necessary limb length and desired alignment. RESULTS: Solid union of the lengthening site and sound fusion of the ankle were achieved in all five patients with full and unassisted weight bearing. The mean lengthening was 11.8 cm (range 8-14 cm) and the external fixation index (EFI) was 29.3 days/cm (range 22.8-36.3 days/cm). The mean functional score according to the rating system of the Musculoskeletal Tumour Society was 88% (83-90%). One patient showed poor response to chemotherapy, had local recurrence of sarcoma one year after plating, and was treated with above-knee amputation. CONCLUSIONS: In carefully selected patients with primary distal tibial sarcomas, this hybrid method can effectively eliminate tumor lesion, reconstruct function, and shorten the length of wearing an external fixator by a meticulous conversion to internal fixator.

Fingertip Replantation With Palmar Venous Anastomoses in Children.

BACKGROUND: Fingertip amputation in children is difficult to manage using microsurgical replantation techniques and many salvage procedures have failed owing to the nonavailability of suitable veins for anastomosis in the fingertip. This study reviewed our experience of pediatric fingertip replantation involving palmar venous anastomoses and evaluated the clinical outcomes. METHODS: From October 2008 to May 2013, 21 pediatric fingertips that had been completely amputated at or distal to the distal interphalangeal joint of the finger, or at or distal to the interphalangeal joint of the thumb were managed using complete replantation. One artery was anastomosed for revascularization with or without nerve repair, and a palmar venous anastomosis was performed to reestablish the outflow system. RESULTS: Twenty (95.2%) of the 21 fingertips survived. One replant involving an avulsion amputation of the left little finger failed, and the patient underwent stump cap-plasty. Excellent restoration of finger motion, pinch strength, and appearance was observed during the mean 39.9-month (range, 18-65 months) follow-up. The mean regained static 2-point discrimination sensation was 3.8 mm (range, 3.2-4.2 mm). All of the children and their families were satisfied with the surgical outcomes. CONCLUSIONS: Successful palmar venous anastomosis appears to promote the survival of replanted fingertips in children. Given that the procedure may simplify postoperative care, minimize complications, and achieve a high survival rate, it should be attempted if the technical expertise is available.

The Combined Use of a Neurocutaneous Flap and the Ilizarov Technique for Reconstruction of Large Soft Tissue Defects and Bone Loss in the Tibia.

BACKGROUND: Management of posttraumatic large soft tissue defects and bone loss remains a therapeutic and surgical challenge for orthopedic surgeons. We assessed the use of a neurocutaneous flap and the Ilizarov technique in the reconstruction of severe composite defects in the tibia. METHODS: We retrospectively reviewed 18 consecutive patients with trauma-related soft tissue defects and bone loss. The size of the soft tissue defect ranges from 8 × 9 cm to 14 × 18 cm. The mean size of bone loss was 4.5 cm. A great saphenous neurocutaneous flap or sural neurocutaneous flap was created to reconstruct the soft tissue defect. The Ilizarov external fixator was applied to reconstruct bony loss by means of distraction osteogenesis. RESULTS: The mean follow-up period was 38.8 months. All transferred flaps survived completely. The area covered ranged from 9 × 10 cm to 15 × 20 cm. The mean distraction length and duration of use of the external fixator were 6 cm and 11.4 months, respectively. All patients achieved final union. Complications of superficial pin-tract infections and mild Achilles tendon contracture were observed, but these were resolved over time. All patients were satisfied with the outcome of the surgery. CONCLUSIONS: A well-vascularized neurocutaneous flap is a safe and effective option in lower extremity reconstruction under a stable mechanical environment, which can be created using the Ilizarov technique. It is a good option for reconstructing severe complex defects in the lower limb.

Stimulation of Nitric Oxide Production Contributes to the Antithrombotic Effect of Stromal Cell-Derived Factor-1α in Preventing Microsurgical Anastomotic Thrombosis.

Background Intimal injury plays a critical role in initiating the pathogenesis of thrombosis formation after microsurgical anastomosis. Application of stromal cell-derived factor-1α (SDF-1α) is reported to promote early regeneration of injured intima through migration of endothelial cells and mobilization of endothelial progenitor cells. We therefore hypothesized that local transfer of SDF-1α gene would inhibit microsurgical anastomotic thrombosis. Methods Sixty Sprague-Dawley rats were used and divided randomly into three groups (SDF-1α group, plasmid group, and saline group) in this study. Plasmid DNA encoding SDF-1α, empty plasmid, and saline were injected into the left femoral muscles of rats from each group, respectively. Seven days after injection, peripheral blood samples were obtained to measure the plasma levels of SDF-1α and nitric oxide (NO). The left femoral artery of each rat was crushed, transected, and repaired by end-to-end microsurgical anastomosis. Vascular patency was assessed at 15, 30, and 120 minutes after reperfusion using milk test. Thrombosis formation was assessed with hematoxylin and eosin staining and scanning electron microscopy at 120 minutes postoperatively. Results The plasma levels of SDF-1α and NO in SDF-1α group were significantly higher than those in plasmid group and saline group (p < 0.01). The patency rate in SDF-1α group was significantly higher than that in control groups at 120 minutes after reperfusion (p < 0.05). Treatment of SDF-1α significantly reduced the size of thrombotic occlusion when compared with controls (p < 0.05). All SDF-1α recipients exhibited decreased thrombosis under scanning electron microscopy. Conclusions The current study demonstrated that local transfer of SDF-1α gene increases arterial patency and inhibits microsurgical anastomotic thrombosis in a crush model of femoral artery in rat. The antithrombotic effect of SDF-1α may be mediated through increased production of endogenous NO. These findings provide a novel approach for inhibition of microsurgical anastomotic thrombosis.

Lentivirus-mediated Wnt10b overexpression enhances fracture healing in a rat atrophic non-union model.

Lentivirus vectors encoding Wnt10b gene (LV-Wnt10b) or luciferase gene (LV-luc) were constructed to determine whether Wnt10b overexpression improved fracture healing in a rat atrophic non-union model. After fracture, rats were injected with LV-Wnt10b or LV-luc. Luciferase signals were clearly detected. At 2 and 4 weeks, LV-Wnt10b group had 107 and 98% more proliferating cell nuclear antigen (PCNA) positive cells, respectively, and promoted expression of bone morphogenetic protein-2 (BMP-2) in the callus compared with controls. LV-Wnt10b injection significantly increased bone mass density and bone mineral content: 46-84 and 96-193%, respectively, at the site of fracturein the LV-Wnt10b group compared with controls. At 8 weeks, fractured femora were healed in the LV-Wnt10b group compared with atrophic non-unions formed in controls. Thus, Wnt10b overexpression associated with lentiviral gene therapy is effective in healing atrophic non-unions in rats.

Superficial peroneal neurocutaneous flap based on an anterior tibial artery perforator for forefoot reconstruction.

The distally based superficial peroneal neurocutaneous (SPNC) island flap has been widely used for foot reconstruction. It is based on the descending branch of the peroneal artery perforator. However, damage to the perimalleolar vascularization or anatomic variations of the descending branch often causes flap necrosis. Because septocutaneous perforators from the anterior tibial artery participate in the vascular network of superficial peroneal nerve in the distal lower leg, a modified SPNC flap is designed based on the anterior tibial artery perforator. Seven patients with soft tissue defect over the forefoot were treated by this modified technique. Six patients had accompanied injuries at the lateral perimalleolar region, and 1 patient had an anatomic variation of the descending branch of the peroneal artery perforator. The size of defect ranged from 12 × 5 to 15 × 9 cm. All 7 flaps survived completely without complications. The size of the flaps ranged from 13 × 6 to 16 × 10 cm. No severe venous congestion occurred. The mean follow-up was 9.4 months (range, 6-14 months). All patients were satisfied with the texture and color of the flaps. Two patients complained about the thickness of the flaps, but did not want further operation. The donor sites healed uneventfully and no painful neuroma occurred. In conclusion, the modified SPNC flap based on an anterior tibial artery perforator is a feasible salvage procedure when the traditional design is unreliable. It can provide sufficient and superior coverage for large forefoot defect.

Combined Anterolateral Thigh and Anteromedial Thigh Flap for Extensive Extremity Reconstruction: Vascular Anatomy and Clinical Application.

BACKGROUND: The combined anterolateral thigh (ALT) and anteromedial thigh (AMT) flap has been previously reported for use in complicated head and neck reconstruction. However, it has not gained popularity due to the vascular variation. Here, we explore the vascular basis of this combined flap, and report its application in extremity reconstruction. METHODS: This study was divided into two parts: vascular anatomy and clinical application. In the anatomical study, 52 sides of adult thighs were dissected to identity vascular perforators supplying the combined ALT and AMT flap, with focus on sizeable perforators (larger than 0.5 mm) arising from the descending branch of the lateral circumflex femoral artery.Clinically, five male patients were treated by combined ALT and AMT flaps for extensive extremity reconstruction from January 2006 to December 2010. The mean age was 32 years (range, 23-45 years). The combined flap was used for covering large soft-tissue defects in forearm (n = 3) and calf (n = 2). For each patient, esthetic and functional results were recorded. RESULTS: The anatomical study showed that sizeable perforators supplying the ALT flap were present in 50 thighs (96.2%), and the perforators supplying the AMT flap were present in 32 thighs (61.5%). The combined ALT and AMT flaps were available in 30 thighs (57.7%).All five combined flaps survived completely. Skin grafts covering the donor sites healed uneventful. The mean follow-up was 9.6 months (range, 6-12 months). No complications were recorded during the follow-up. CONCLUSION: The combined ALT and AMT flap may be used for extensive extremity reconstruction in selected patients for its great maneuverability and acceptable donor-site morbidity.

A "hybrid" sural flap for treatment of chronic calcaneal osteomyelitis.

BACKGROUND: The treatment of chronic calcaneal osteomyelitis remains a challenge for orthopedic and plastic surgeons. The basis of surgical therapy includes thorough debridement of infected tissue and reconstruction with well-vascularized flaps. METHODS: A "hybrid" sural flap composed of an adiponeurofascial flap proximally and a neurofasciocutaneous flap distally is described here. The adiponeurofascial flap was used to obliterate the bone cavity, and the distal part was used to resurface soft tissue defects. Five patients with chronic calcaneal osteomyelitis were treated with this modified sural flap. RESULTS: The size of the adiponeurofascial flap ranged from 5.0 × 4.0 cm to 13.0 × 5.0 cm, and that of the neurofasciocutaneous flap ranged from 6.5 × 3.0 cm to 6.0 × 8.0 cm. The donor defects were covered with skin grafts in three patients and closed primarily in two patients. All the flaps survived completely without any complications, the skin graft and the skin over the adiponeurofascial flap healed uneventfully. There was no evidence of recurrent infection during the follow-up period. CONCLUSION: The modified "hybrid" sural flap is simple and reliable and is a good candidate for treatment of chronic calcaneal osteomyelitis.

Distally based saphenous neurocutaneous perforator flap combined with vac therapy for soft tissue reconstruction and hardware salvage in the lower extremities.

The complex wound with the exposed hardware and infection is one of the common complications after the internal fixation of the tibia fracture. The salvage of hardware and reconstruction of soft tissue defect remain challenging. In this report, we presented our experience on the use of the distally based saphenous neurocutaneous perforator flap combined with vacuum-assisted closure (VAC) therapy for the coverage of the soft tissue defect and the exposed hardware in the lower extremity with fracture. Between January 2008 and July 2010, seven patients underwent the VAC therapy followed by transferring a reversed saphenous neurocutaneous perforator flap for reconstruction of the wound with exposed hardware around the distal tibia. The sizes of the flaps ranged from 6 × 3 cm to 15 × 6 cm. Six flaps survived completely. Partial necrosis occurred in one patient. There were no other complications of repair and donor sites. Bone healing was achieved in all patients. In conclusion, the reversed saphenous neurocutaneous perfortor flaps combined with the VAC therapy might be one of the options to cover the complex wound with exposed hardware in the lower extremities.

Medial sural artery perforator flap.

In the last decade, the medial sural artery perforator flap (MSAP) has emerged as one of the most popular reconstructive options for multiple body sites. The versatility of the flap hinges on the ability to harvest multiple tissue components in various combinations but from the same wound. The flap can be used as a pedicled, free, or chimeric design, or even may be used in sequential order. Anatomic anomalies of these perforators are rare compared with other perforator flaps, but well-prepared preoperative planning and the identification of perforators remain the cornerstone of successful flap harvest. So far, the MSAP has been proved to be an excellent alternative for skin resurfacing and functional reconstruction in head and neck as well as in the extremities. In this review, the anatomy, preoperative planning and flap design, harvest technique, and its clinical application in multiple body sites are summarized. Both the advantages and disadvantages are also included.

N klA Case Report on a IV-degree Thermal Crush Injury of Right Upper Arm: The Application of Functional Prosthesis Implantation Technology.

Severe IV-degree thermal crush injury of limbs involved the subcutaneous fascia, muscle and bone, which may lead to amputation and has a great impact on the patient's quality of life. We can repair wounds with pedicle flaps or even free flaps, However, there are still huge challenges in bone defect of extremities and functional reconstruction. In recent years, with the development of functional prostheses, we have reconstructed limb functions in many patients helping them to complete their daily lives. We report a case where the right upper arm was injured by thermal crush, leading severe burns to the skin, fascia, muscle and bone. We applied a pedicled latissimus dorsi flap and a free anterolateral thigh flap to repair the wound, and realized the function of limb salvage and movement of the right upper arm by implanting 3D printed scapula, upper arm, and elbow joint prostheses. This case illustrates that IV-degree burns involving bones have new technologies to repair and achieve mobility now.

Combined medialis pedis and medial plantar fasciocutaneous flaps based on the medial plantar pedicle for reconstruction of complex soft tissue defects in the hand.

The reconstruction of complex soft tissue defects in hands remains a difficult challenge in reconstructive surgery. In this report, we introduce a combined medialis pedis and medial plantar fasciocutaneous flaps supplied by the lateral and medial branches of the medial plantar artery, which allows a one-stage reconstruction of multiple soft tissue defects in hand. Three combined medialis pedis and medial plantar fasciocutaneous flaps were transferred for repair of the soft tissue defects including palmar and dorsal areas of hand, thumb pulp, and the dorsum of index finger in three patients. All three flaps survived uneventfully with coverage matching the texture and color of the recipients. The donor sites healed without complication. The experience from these cases proves that the combined medialis pedis and medial plantar fasciocutaneous flaps based on the medial plantar pedicle would be a valuable alternative for the reconstruction of complex soft tissue defects in the hand.

Triple endobuttton technique for the treatment of acute complete acromioclavicular joint dislocations: preliminary results.

Numerous procedures have been described for the operative management of acromioclavicular (AC) joint injuries. Some of these techniques, including hardware fixation and non-anatomical reconstructions, are associated with serious complications and high failure rates. Recently, AC joint reconstruction techniques have focused on anatomical restoration of the coracoclavicular ligaments to achieve optimal clinical outcomes. We used a triple endobutton technique to separately reconstruct the trapezoid and the coronoid portions of the coracoclavicular ligament. We evaluated the preliminary clinical and radiological results of this technique in patients with acute complete dislocation of the AC joint. All patients achieved a significant improvement in the pain and function of shoulder at a mean follow-up interval of 12 months (range, 8-14 months). Excellent reduction of the AC joint was maintained. The triple endobutton technique may be safe and effective for the treatment of acute complete AC joint dislocations.

The extended peroneal artery perforator flap for lower extremity reconstruction.

The peroneal artery perforator flap and its modifications have been widely used for coverage of soft tissue defects of ankle and foot in the past decade. In this article, we report on a series of upper knee, ankle, and foot reconstructions with a proximally or distally based extended peroneal artery perforator (EPAP) flap supplied by distinct perforating branches off the proximal or distal peroneal artery. Total pedicle length obtained ranged from 6 to 12 cm. Twelve patients with soft tissue defects of the lower extremity underwent reconstruction using the EPAP flap. The flaps were designed with the sizes from 10 x 6 cm to 25 x 15 cm. All 12 flaps survived completely without complications. Our experience demonstrates that the EPAP flap is reliable and versatile and can provide a large amount of soft tissue for coverage of defects in the leg anywhere from knee to forefoot obviating the need for free tissue transplantation.

Peroneal artery perforator chimeric flap for reconstruction of composite defects in extremities.

Large bone defects of extremities, especially those associated with soft tissue defects, represent difficult reconstructive problems. Chimeric flap is a suitable option for reconstruction of complex bone and soft-tissue defects. In this report, we present the experience on use of the peroneal artery perforator chimeric flap for the reconstruction of complex bone and soft tissue defects in the extremities in 16 patients. The bone defects were located in the tibia in 8 patients, in both tibia and fibula in 1 patient, in the ulna in 2 patients, in both ulna and radius in 2 patients, and the metatarsal bone in 3 patients. The flap was created with skin paddle and fibula bone segments based on independent perforators. The sizes of flap ranged from 8 x 6 to 20 x 11 cm(2), and the length of fibular grafts ranged from 6 to 22 cm. All flaps survived completely. Bone union was ultimately obtained in all cases at 5 to 11 months, while two cases suffered from stress fractures in 12 month and 18 month after operation, respectively, which eventually healed with external fixation treatment. The follow-up time ranged from 12 to 37 months. The definite bone hypertrophy was observed from X-ray at 18 months after operation. In conclusion, our results show that the peroneal artery perforator chimeric flap is a good option for reconstruction of complex bone and soft-tissue defects of extremities, particularly for those with three-dimensional defects and bone defects exceeding 6 cm in length.

Clinical outcomes of midclavicular fractures treated with titanium elastic nails.

BACKGROUND: Midclavicular fractures are common clinically, accounting for about 76% of all clavicular fractures. Recent studies have revealed a previously unrecognized incidence of nonunion and malunion after conservative treatment of more severe midclavicular fractures. Our aim was to evaluate the clinical outcomes of midclavicular fractures treated with titanium elastic nails. METHODS: From February 2005 to February 2007, 41 patients with displaced midclavicular fractures received open reduction and internal fixation with a titanium elastic nail inserted through the sternal end of the clavicle. We evaluated the visual analogue scale (VAS), the Constant score and the Disabilities of the Arm, Shoulder and Hand (DASH) scale to determine outcomes. RESULTS: A mean follow-up of 14.5 months (range 7-24 mo) revealed radiographic fracture union in all patients with an average clinical healing time of 2.2 months. Mean subjective pain 3 days after surgery was significantly lower than the day before surgery (p < 0.001). The mean range of motion 3 days after surgery was significantly improved compared with the day before surgery (p < 0.001). The nails were removed in all patients a mean of 7.2 months (range 5.4-9.5 mo) after surgery, and no fractures recurred. The mean postoperative DASH score was 2.5 (range 0.5-8.0) and the mean postoperative Constant score was 95.2 (range 86.5-97.0). CONCLUSION: Limited open reduction and internal fixation with titanium elastic nails is a safe and minimally invasive surgical procedure for the treatment of displaced midclavicular fractures in adults and achieves good functional results and high patient satisfaction.

Poly (Glycerol Sebacate)-Based Bio-Artificial Multiporous Matrix for Bone Regeneration.

In recent years, bone repair biomaterials that combine cells and bioactive factors are superior to autologous and allogeneic bone implants. However, neither natural nor synthetic biomaterials can possess all desired qualities such as strength, porosity, and biological activity. In this study, we used poly (glycerol sebacate) (PGS), a synthetic material with great osteogenic potential that has attracted more attention in the field of tissue (such as bone tissue) regeneration owing to its good biocompatibility and high elasticity. It also has the advantage of being regulated by material synthesis to match the bone tissue's strength and can be easily modified to become functional. However, pure PGS lacks functional groups and hydrophilicity. Therefore, we used PGS as the substrate to graft the adhesive ligands RGD and vascular endothelial growth factor mimetic peptide. The bone repair scaffold can be prepared through photo crosslinking, as it not only improves hydrophobicity but also promotes vascularization and accelerates osteogenesis. Simultaneously, we improved the preparation method of hydrogels after freeze-drying and crosslinking to form a sponge-like structure and to easily regenerate blood vessels. In summary, a bone repair scaffold was prepared to meet the structural and biological requirements. It proved to serve as a potential bone-mimicking scaffold by enhancing tissue regenerative processes such as cell infiltration and vascularization and subsequent replacement by the native bone tissue.

Docosahexaenoic Acid Improves Diabetic Wound Healing in a Rat Model by Restoring Impaired Plasticity of Macrophage Progenitor Cells.

BACKGROUND: Chronic inflammation associated with delayed diabetic wound healing is induced by disturbed polarization of macrophages derived mainly from predisposed progenitor cells in bone marrow. Docosahexaenoic acid plays a critical role in regulating the function of macrophage progenitor cells. The authors evaluated whether docosahexaenoic acid accelerates diabetic wound healing in rats. METHODS: Streptozotocin-induced diabetic rats divided into control and docosahexaenoic acid-treated groups (n = 10) were subjected to paired dorsal skin wounds. Docosahexaenoic acid (100 mg/kg per day) was orally supplemented 2 weeks before wounding until termination. The wound healing process was recorded 0, 7, and 14 days after wounding. At day 7, blood perfusion was measured by laser Doppler perfusion imaging; angiogenesis was compared using immunofluorescent CD31 and α-smooth muscle actin staining; macrophage polarization was detected using immunofluorescence for CD68, CD206, and inducible nitric oxide synthase. Hematoxylin and eosin staining was used to examine wound healing at day 14. Activation status of macrophages derived from bone marrow cells in normal, diabetic, and docosahexaenoic acid-treated diabetic rats was determined in vitro using Western blotting and enzyme-linked immunosorbent assay. RESULTS: Docosahexaenoic acid significantly accelerated wound healing 7 and 14 days (p < 0.01) after wounding. Increased vessel densities (1.96-fold; p < 0.001) and blood perfusion (2.56-fold; p < 0.001) were observed in docosahexaenoic acid-treated wounds. Immunofluorescence revealed more CD206 and fewer inducible nitric oxide synthase-positive macrophages (p < 0.001) in treated wounds. Furthermore, macrophages derived from diabetic rats expressed higher levels of inducible nitric oxide synthase and tumor necrosis factor-α and lower arginase-1 and interleukin-10 (p < 0.05). CONCLUSION: Docosahexaenoic acid accelerates diabetic wound healing at least in part by restoring impaired plasticity of macrophage progenitor cells.

Chinese expert consensus on diagnosis and treatment of infection after fracture fixation.

Currently, accurate diagnosis and successful treatment of infection after fracture fixation (IAFF) still impose great challenges. According to the onset of infection symptoms after implantation, IAFF is classified as early infection (<2 weeks), delayed infection (2∼10 weeks) and late infection (>10 weeks). Confirmation of IAFF should be supported by histopathological tests of intraoperative specimens which confirm infection, cultures from at least two suspected infection sites which reveal the same pathogen, a definite sinus or fistula which connects directly the bone or the implant, and purulent drainage from the wound or presence of pus during surgery. Diagnosis of IAFF is built on comprehensive assessment of medical history, clinical signs and symptoms of the patient, and imaging and laboratory tests. The gold standard of diagnosis is histopathological tests. Treatment of IAFF consists of radical debridement, adequate irrigation, implant handling, systematic and local antibiotics, reconstruction of osseous and/or soft tissue defects, and functional rehabilitation of an affected limb. Early accurate diagnosis and appropriate treatment of IAFF play a key role in increasing the cure rate, reducing infection recurrence and disability risk, restoring limb function and improving quality of life of the patient.

Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT/mTOR pathway.

BACKGROUND: Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidate agents for treating critical-sized bone defects; they promote angiogenesis and may be an alternative to cell therapy. In this study, we evaluated whether exosomes derived from bone marrow-derived MSCs (BMSCs) preconditioned with a low dose of dimethyloxaloylglycine (DMOG), DMOG-MSC-Exos, exert superior proangiogenic activity in bone regeneration and the underlying mechanisms involved. METHODS: To investigate the effects of these exosomes, scratch wound healing, cell proliferation, and tube formation assays were performed in human umbilical vein endothelial cells (HUVECs). To test the effects in vivo, a critical-sized calvarial defect rat model was established. Eight weeks after the procedure, histological/histomorphometrical analysis was performed to measure bone regeneration, and micro-computerized tomography was used to measure bone regeneration and neovascularization. RESULTS: DMOG-MSC-Exos activated the AKT/mTOR pathway to stimulate angiogenesis in HUVECs. This contributed to bone regeneration and angiogenesis in the critical-sized calvarial defect rat model in vivo. CONCLUSIONS: Low doses of DMOG trigger exosomes to exert enhanced proangiogenic activity in cell-free therapeutic applications.