Repair of sciatic nerve defects using tissue engineered nerves

In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination with bone marrow mesenchymal stem cells of Wistar rats cultured in vitro, to repair 15 mm sciatic bone defects in Wistar rats. At postoperative 12 weeks, electrophysiological detection results showed that the conduction velocity of regenerated nerve after repair with tissue-engineered nerves was similar to that after autologous nerve grafting, and was higher than that after repair with acellular nerve allografts. Immunohistochemical staining revealed that motor endplates with acetylcholinesterase-positive nerve fibers were orderly arranged in the middle and superior parts of the gastrocnemius muscle; regenerated nerve tracts and sprouted branches were connected with motor endplates, as shown by acetylcholinesterase histochemistry combined with silver staining. The wet weight ratio of the tibialis anterior muscle at the affected contralateral hind limb was similar to the sciatic nerve after repair with autologous nerve grafts, and higher than that after repair with acellular nerve allografts. The hind limb motor function at the affected side was significantly improved, indicating that acellular nerve allografts combined with bone marrow mesenchymal stem cell bridging could promote functional recovery of rats with sciatic nerve defects.

Repair of bile duct defect with degradable stent and autologous tissue in a porcine model

AIM： To introduce and evaluate a new method to re- pair bile duct defect with a degradable stent and au- tologous tissues. METHODS： Eight Ba-Ma mini-pigs were used in this study, Experimental models with common bile duct （CBD） defect （0,5-1,0 cm segment of CBD resected） were established and then CBD was reconstructed by duct to duct anastomosis with a novel degradable stent made of poly [sebacic acid-co-（1,3-propanediol）-co- （1,2-propanediol）]. In addition, a vascularized greater omentum was placed around the stent and both ends of CBD. Cholangiography via gall bladder was per- formed for each pig at postoperative months 1 and 3 to rule out stent translocation and bile duct stricture. Complete blood count was examined pre- and post- operatively to estimate the inflammatory reaction. Liver enzymes and serum bilirubin were examined pre- and post-operatively to evaluate the liver function. Five pigs were sacrificed at month 3 to evaluate the healing of anastomosis. The other three pigs were raised for one year for long-term observation. RESULTS： All the animals underwent surgery success- fully. There was no intraoperative mortality and no bile leakage during the observation period, The white blood cell counts were only slightly increased on day 14 and month 3 postoperatively compared with that before operation, the difference was not statistically significant （P = 0.652）. The plasma level of alanine aminotrans- ferase on day 14 and month 3 postoperatively was also not significantly elevated compared with that before operation （P = 0.810）. Nevertheless, the plasma level of y-glutamyl transferase was increased after opera- tion in both groups （P = 0.004）, especially 2 wk after operation. The level of serum total bilirubin after opera- tion was not significantly elevated compared with that before operation （P = 0.227）, so did the serum direct bilirubin （P = 0.759）. By cholangiography yia gall blad- der, we found that the stent maintained its integrity of shape and was stillin situ at month 1, and it disap- peared completely at month 3. No severe CBD dilation and stricture were observed at both months 1 and 3. No pig died during the 3-too postoperative observation period. No sign of necrosis, bile duct stricture, bile leak- age or abdominal abscess was found at reoperation at month 3 postoperatively. Pigs had neither fragments of stent nor stones formed in the CBD. Collagen deposit was observed in the anastomosis by hematoxylin and eosin （HE） and Masson＇s trichrome stains. No severe cholestasis was observed in liver parenchyma by HE staining. Intestinal obstruction was found in a pig 4 mo after operation, and no bile leakage, bile duct stricture or biliary obstruction were observed in laparotomy. No sign of bile duct stricture or bile leakage was observed in the other two pigs. CONCLUSION： The novel method for repairing bile duct defect yielded a good short-term effect without postoperative bile duct stricture. However, the long- term effect should be further studied.

Versatility of Reverse Sural Fasciocutaneous Flap for Reconstruction of Distal Lower Limb Soft tissue Defects

Summary： In this study we present our experiences with the reverse sural fasciocutaneous flap to reconstruct the distal lower limb soft tissue defects caused by traumatic injuries. These flap graftings were carried out from Oct. 2010 to Dec. 2012 in our department. The series consisted of 36 patients, including 21 men and 15 women with an average age of 46.2 years （14-83 years） and with a medium followp period of 18 months （12-24 months）. Of all the cases of acute trauma, there were 10 eases of trauma of distal tibia, 9 cases of trauma of perimalleolus, and 17 cases of trauma of midfoot and forefoot. Related risk factors in the patients were diabetes （2 cases）, advanced age （〉65 years, 3 cases） and ciga- rette smoking （6 cases）. The reverse flow sural island flap irrigation depended on lower perforators of the peroneal artery. The fasciocutaneous pedicle was 3-4 cm in width and the anatomical structures consisted of the superficial and deep fascia, the sural nerve, short saphenous vein, superficial sural artery together with an islet of subcutaneous cellular tissue and skin. The most proximal border of the flap was only 1.5 cm away from the popliteal skin crease and the pivot point was 5-7 cm above the tip of the lateral malleolus. All the flaps survived. No arterial crisis occurred in any case. The venous congestion occurred in 2 cases and got better after raising the limbs and bloodletting. Only in an old man, 1.5 cm necrosis of distal margin of his flap occurred and finally healed after continuous dressing change. One-stage skin grafting was performed, and all the donor sites were sutured and successfully healed. It was concluded that the reverse sural fasciocutaneous flap is safe and reliable to extend to the proximal third even near the popliteal skin crease. We also concluded this flap can be safely and efficiently used to treat patients with large and far soft-tissue defects from the distal leg to the forefoot with more versatility and it is easier to reach the recipient sites.

A new method for intraoral tissue defect repair:diepithelialized tissue flap with vascular anastomosis

Diepithelialized tissue flap(DTF)with vascular anastomosis was de-signed in August 1987,and was used for the repair of 12 cases of large intraoraltissue defect.All the operations were successful.The clinical data were reportedand the procedure to incise and transplant a DTF described.When the healingprocess and changes of DTF after transplantation were observed,it was foundthat a layer of new smooth epidermis was formed on the surface of the DTF.Theorigin of this new epidermis was discussed.Ten out of the 12 cases have been fol-lowed up for from half a year to 2 and a half years,and the results weresatisfactory.The new epidermis showed no hair growth and the patients did nothave any rough feeling,which usually occurred after ordinary skin grafting.It isbelieved that DTF transplantation is likely an ideal method for the repair andreconstruction of intraoral soft tissue defect.Its disadvantage was that the DTFcontracted severely after healing.Finally the authors put forward the problemsconcerning the transplantation of DTF,which should be investigated further.

Experimental study on early repair of oromaxillofacial perforating soft tissue defect due to gunshot in dogs

The left cheek of 8 adult male mongrel dogs was shot with M1935.56mm bul-let fired through an US-made M16 rifle to result in a perforating soft tissue defect.Pri-mary debridement was performed immediately and the secondary debridement 72h alter in-jury.After the secondary thorough debridement,the cutaneous side of the defect was re-paired with a saphenous artery-vein free skin(muscular)flap using microvascularanastomosis,and the oral side of the defect was repaired by drawing the surroundingmucosa together and fixing with sutures or with a local sliding mucous membrane flap.All the animals were kept under observation for 2～6 months.It was believed that the pri-mary debridement and secondary thorough debridement were both essential. The survivalrate of the free tissue flap was 75%(6/8).These facts suggest that early repair ofthe oromaxillofacial perforating soft tissue defect due to gunshot is practicable.

Experimental Study on Low Intensity Ultrasound and Tissue Engineering to Repair Segmental Bone Defects

In order to evaluate the efficacy of low intensity ultrasound and tissue engineering technique to repair segmental bone defects, the rabbit models of 1.5-cm long rabbit radial segmental osteoperiosteum defects were established and randomly divided into 2 groups. All defects were implanted with the composite of calcium phosphate cement and bone mesenchymal stem cells, and ad- ditionally those in experimental group were subjected to low intensity ultrasound exposure, while those in control group to sham exposure. The animals were killed on the postoperative week 4, 8 and 12 respectively, and specimens were harvested. By using radiography and the methods of biomechanics, histomorphology and bone density detection, new bone formation and material degradation were observed. The results showed that with the prolongation of time after operation, serum alkaline phosphatase （AKP） levels in both groups were gradually increased, especially in experimental group, reached the peak at 6th week （experimental group： 1,26 mmol/L; control group： 0.58 mmol/L）, suggesting the new bone formation in both two group, but the amount of new bone formation was greater and bone repairing capacity stronger in experimental group than in control group. On the 4th week in experimental group, chondrocytes differentiated into woven bone, and on the 12th week, remodeling of new lamellar bone and absorption of the composite material were observed. The mechanical strength of composite material and new born density in experimental group were significantly higher than in control group, indicating that low intensity ultrasound could not only effectively increase the formation of new bone, but also accelerate the calcification of new bone. It was concluded that low intensity ultrasound could evidently accelerate the healing of bone defects repaired by bone tissue engineering.

Experimental study of trabecular tissue repair for corneal defect in rabbits

AIM:To investigate the mechanism and effect of trabecular tissue repair for corneal defect,and to provide a theoretical basis for its clinical application.METHODS:Trabeculectomy was performed on 40(80 eyes)of 70 New Zealand white rabbits.Take trabecular tissue for backup.Thirty(30 eyes)corneal defect models were made,trabecular tissue was filled in the corneal defect,and the oblique cross stitch was used to suture the corneal laceration and debridement.Anterior segment image and optical coherence tomography(OCT)were performed at the time 1 d,1 wk,1 and 3 mo after the model was made.After the observation,the cornea was to ken and stained with trypanosome blue-alizarin red and the pathological tissue was examined.RESULTS:Observation 1 wk after surgery,the area of corneal defect was edema,but the corneal curvature was basically normal,and the anterior chamber existed under slit lamp.After 3 mo of observation,most corneal defects were repaired in the form of corneal leucoma and corneal macula(73.3%),the filled trabecular tissue gradually became transparent,fused tightly with the corneal tissue,and the corneal curvature was relatively smooth.But in one case,the trabecular planter was partially detached,no serious complications such as corneal laceration occurred after the stitches were removed.CONCLUSION:The trabecular tissue structure is similar to the corneal,and it can be used as a substitute for the corneal tissue defect by providing fiber scaffolds and cell amplification differentiation,and lay a foundation for the second-stage surgical treatment.

Possible mechanism of 15D-PGJ2 in promoting periodontal tissue regeneration in patients with mandibular defects

Objective:To explore the main physiological mechanism of 15d-PGJ2 promoting periodontal tissue regeneration in patients with jaw defects caused by periodontal disease.Methods:From February 2016 to July 2019,a controlled study was conducted on 73 healthy residents(healthy group)and 73 patients(case group)with periodontal disease combined with jaw defects in Changsha medical university.T test was used to compare the growth factors of gingival crevicular fluid between the two groups.Peripheral blood cells;Cement-specific protein;Peripheral blood enzyme;Statistical differences in bone metabolites.The t test method compared the content of each index before and after treatment(15d-PGJ2 was treated at a dose of 200 mu/kg for 14 days).The method of factor analysis explores the internal correlation of each index.Result:RANKL,ICAM-1,TGF-β1,Th17,Treg,PDLSCs,SOST,CAP,HMGB1,CTSK,5-LOX,COX-2,NTX were higher in the case group than in the healthy group.In the case group,RANKL,ICAM-1,TGF-β1,Th17,Treg,PDLSCs,SOST,CAP,HMGB1,CTSK,5-LOX,COX-2,NTX were lower than those in the healthy group.The differences between the groups were statistically significant(P<0.05).Compared with before treatment,IL-1β,IL-17,Bfgf,YKL-40,BMP-2,ICTP,PICP,CTX were significantly decreased after treatment.RANKL,ICAM-1,TGF-β1,Th17,Treg,PDLSCs,SOST,CAP,HMGB1,CTSK,5-LOX,COX-2,NTX were significantly increased.The differences were statistically significant(P<0.05).Factor analysis shows that four common factors can be extracted from 21 indicators,and the cumulative contribution rate is 96.993%.Conclusions:The treatment of 15d-PGJ2 in patients with periodontal disease with maxillary defects can significantly affect the expression of multiple characteristic indicators,which may involve four mechanisms:dysregulation of cell differentiation or migration,local inflammation or immune imbalance,destruction of alveolar bone microstructure,load or stimulation,and remodeling.The specific pathway related to this is still to be further explored.

Repair of Sheep Metatarsus Defects by Using Tissue-engineering Technique

Tissue-engineering bone with porous β-tricalcium phosphate (β-TCP) ceramic and autologous bone marrow mesenchymal stem cells (MSC) was constructed and the effect of this composite on healing of segmental bone defects was investigated. 10-15 ml bone marrow aspirates were harvested from the iliac crest of sheep, and enriched for MSC by density gradient centrifugation over a Percoll cushion (1.073 g/ml). After cultured and proliferated, tissue-engineering bones were constructed with these cells seeded onto porous β-TCP, and then the constructs were implanted in 8 sheep left metatarsus defect (25 mm in length) as experimental group. Porous β-TCP only were implanted to bridge same size and position defects in 8 sheep as control group, and 25 mm segmental bone defects of left metatarsus were left empty in 4 sheep as blank group. Sheep were sacrificed on the 6th, 12th, and 24th week postoperatively and the implants samples were examined by radiograph, histology, and biomechanical test. The 4 sheep in blank group were sacrificed on the 24th week postoperatively. The results showed that new bone tissues were observed either radiographic or histologically at the defects of experimental group as early as 6th week postoperatively, but not in control group, and osteoid tissue, woven bone and lamellar bone occurred earlier than in control group in which the bone defects were repaired in “creep substitution” way, because of the new bone formed in direct manner without progression through a cartilaginous intermediate. At the 24th week, radiographs and biomechanical test revealed an almost complete repair of the defect of experimental group, only partly in control group. The bone defects in blank group were non-healing at the 24th week. It was concluded that engineering bones constructed with porous β-TCP and autologous MSC were capable of repairing segmental bone defects in sheep metatarsus beyond “creep substitution” way and making it healed earlier. Porous β-TCP being constituted with autologous MSC may be a good option in healing critical segmental bone defects in clinical practice and provide insight for future clinical repair of segmental defect.

Treatment of large defect of abdominal wall after tumors resection by transposition of tissue flaps with pedicle

Objective To report evaluat of division region of abdominal wall large defect after tumors resection and repair methods by tissue flaps with pedicle. Methods Form October 1992 to September 2001, 8 cases large abdominal wall defect after malignant tumors resection(10 × 10 cm-32 cm×32 cm) were reviewed. The defectcontributed:Ⅰ region, 2 cases; twin-Ⅱ region, 2; Ⅲ region, 2; Ⅰ and Ⅱ region of one side, 1 and total abdominal wall,one case, The tissue flaps of transposition included: gracilis myocutaneous flaps, 4; retus abdominal myocutaneous flaps, 2; external abdominal obligue musculo-fascia flaps, 2; latissimus dorsi muscle, tensor fasciae latae muscle and retus femoris muscle flaps each, 1. One patient used MycroMesh also. Results In the course of peroperation, the incisions of 8 cases healed in first time; total tissue flaps survived and all pateints started exercise left the bed in 3 weeks. All 8 patients were followed up average of 2 years and 5 months: the success rate of reconstruction

Applied distally based peroneus brevis muscle flaps for coverage of the soft tissue defects over the lower one-third of the leg, ankle and foot

Objective To investigate a simple, valuable new method for coverage of the soft tissue defect over the lower one-third of the leg, ankle and the foot. Methods The distally based peroneus brevis muscle fkps were applied for coverage of the soft tissue defects over the lower one-third of the leg,the ankle and the foot. The muscle flaps were covered with split-thickness skin grafts. Results The distally based peroneus brevis muscle flaps were applied for coverage of the soft tissue defects over the lower one-third of the leg, the ankle and the foot in 16 cases. The larges area of the soft tissue defect was 5 cm × 7 cm. The smallest was 3 cm × 4 cm. Primary healing occured in 14 cases undergoing muscle flap construction, second-stage healing occured in 2 cases, no total flap necrosis occured in any cases. Conclusion ThisChina Medical Abstracts(Surgery) technigue is a simple and complication are lesser. The successful rates are higher. This muscle flap is suitable to the mudium or small soft tissue

Lower rotating point nutrient vessels of sural nerve flap with distant pedicled repairing soft tissue defect of foot and ankle

To explore lower rotating potint nutrient vessels of sural nerve flap with distant pedicled repairing the soft tissue defect of foot and ankle.Methods Lay a foundation of anatomic studying from february 2003 to March 2004,using lower rotating point nutrient vessels of sural nerve flap with distant pedicled repairing the soft tissue defect of foot and ankle in 11 cases.Cause of injuring:traffic accident 7 cases,crushing 1 case,saw injury 1 case,skin cancer 1 case,chronic ulcer 1 case.Areas:foot heel 6 cases,shank lower section 2 cases,heel tendon 2 cases,the distant back of the foot 1 case.Using the flap axis point was 1～3 cm above the pin of the external heel,average 2 cm.The scope of the flap was 6.0 cm×8.0 cm～12.0 cm～18.0 cm.Results All sural nerve flaps were alive.Of them,2 cases have distant part necrosis,accompanying with subcutaneous tissue,1 case heels after change dressings,another heels after skin grafting.All case can walk as usual,the flap was wear-resisting and keenly feel.Conclusion Lower rotating point nutrient vessels of sural nerve flap,donner area was fine,available area was large,skin in the pink,easy grafting,without main blood vessel damage,survival rate high,it is a good donner area in repairing around heel,foot and shank lower section.7 refs,1 tab.

Oral and maxillofacial-head and neck reconstruction with soft tissue free flaps of 41 cases: A single team's experience

Objective To retrospectively review the single team's experience of oral and maxillofacialhead and neck reconstruction involving 41 soft tissue free flap procedures.Methods From 1994 to 2012,41 patients who underwent oral and maxillofacial-head and neck soft tissue free flap reconstruction at the Department of Oral and Maxillofacial-Head and Neck Surgical Oncology,Hospital and College of Stomatology,Xi'an Jiaotong University,were reviewed with clinicopathologic data.Results The 41 patients included 24 men and 17 women with a mean age of 54 years.A total of 41 soft tissue free flaps were performed to reconstruct different anatomical structures in the head and neck region including oral mucosa,facial bone,head and neck skin.Two types of soft tissue free flaps were used to reconstruct surgical defects,including radial forearm flap and latissimus dorsi myocutaneous flap.Radial forearm flaps were used for 37cases and latissimus dorsi-myocutaneous flaps were 4 cases.Of 41 cases,39 were successful,with an overall success rate of 95.1%.There were 2 free flap failures,including one radial forearm flap and one latissimus dorsi-myocutaneous flap(partial flap necrosis);hence,the flap success rates for radial forearm flap and latissimus dorsimyocutaneous were,respectively,97.3% and 87.5%.Conclusions Radial forearm flap and latissimus dorsi-myocutaneous flap are reliable soft tissue free flaps to repair oral and maxillofacial-head and neck area with high success rate,which resulted in good functionally and cosmetically with fewer complications both donor and recipient sites.

Molecular Tissue Engineering: Applications for Modulation of Mesenchymal Stem Cells Proliferation by Transforming Growth Factor β_1 Gene Transfer

The effect of transforming growth factor β 1 (TGF β 1 ) gene transfection on the proliferation of bone marrow derived mesenchymal stem cells (MSC S ) and the mechanism was investigated to provide basis for accelerating articular cartilage repairing using molecular tissue engineering technology. TGF β 1 gene at different doses was transduced into the rat bone marrow derived MSCs to examine the effects of TGF β 1 gene transfection on MSCs DNA synthesis, cell cycle kinetics and the expression of proliferating cell nuclear antigen (PCNA). The results showed that 3 μl lipofectamine mediated 1 μg TGF β 1 gene transfection could effectively promote the proliferation of MSCs best; Under this condition (DNA/Lipofectamine=1μg/3μl), flow cytometry and immunohistochemical analyses revealed a significant increase in the 3 H incorporation, DNA content in S phase and the expression of PCNA. Transfection of gene encoding TGF β 1 could induce the cells at G0/G1 phase to S1 phase, modulate the replication of DNA through the enhancement of the PCNA expression, increase the content of DNA at S1 phase and promote the proliferation of MSCs. This new molecular tissue engineering approach could be of potential benefit to enhance the repair of damaged articular cartilage, especially those caused by degenerative joint diseases.

Differentiation of mesenchymal stem cells into neuronal cells on fetal bovine acellular dermal matrix as a tissue engineered nerve scaffold

The purpose of this study was to assess fetal bovine acellular dermal matrix as a scaffold for supporting the differentiation of bone marrow mesenchymal stem cells into neural cells fol-lowing induction with neural differentiation medium. We performed long-term, continuous observation of cell morphology, growth, differentiation, and neuronal development using several microscopy techniques in conjunction with immunohistochemistry. We examined speciifc neu-ronal proteins and Nissl bodies involved in the differentiation process in order to determine the neuronal differentiation of bone marrow mesenchymal stem cells. The results show that bone marrow mesenchymal stem cells that differentiate on fetal bovine acellular dermal matrix display neuronal morphology with unipolar and bi/multipolar neurite elongations that express neuro-nal-speciifc proteins, includingβIII tubulin. The bone marrow mesenchymal stem cells grown on fetal bovine acellular dermal matrix and induced for long periods of time with neural differen-tiation medium differentiated into a multilayered neural network-like structure with long nerve ifbers that was composed of several parallel microifbers and neuronal cells, forming a complete neural circuit with dendrite-dendrite to axon-dendrite to dendrite-axon synapses. In addition, growth cones with filopodia were observed using scanning electron microscopy. Paraffin sec-tioning showed differentiated bone marrow mesenchymal stem cells with the typical features of neuronal phenotype, such as a large, round nucleus and a cytoplasm full of Nissl bodies. The data suggest that the biological scaffold fetal bovine acellular dermal matrix is capable of supporting human bone marrow mesenchymal stem cell differentiation into functional neurons and the subsequent formation of tissue engineered nerve.

Expression of Transforming Growth Factor β_(1) in Mesenchymal Stem Cells: Potential Utility in Molecular Tissue Engineering for Osteochondral Repair

The feasibility of using gene therapy to treat full-thickness articular cartilage defects was investigated with respect to the transfection and expression of exogenous transforming growth factor(TGF)-β_(1)genes in bone marrow-derived mesenchymal stem cells(MSCs)in vitro.The full-length rat TGF-β_(1)cDNA was transfected to MSCs mediated by lipofectamine and then selected with G418,a synthetic neomycin analog.The transient and stable expression of TGF-β_(1)by MSCs was detected by using immunohistochemical staining.The lipofectamine-mediated gene therapy efficiently transfected MSCs in vitro with the TGF-β_(1)gene causing a marked up-regulation in TGF-β_(1)expression as compared with the vector-transfected control groups,and the increased expression persisted for at least 4 weeks after selected with G418.It was suggested that bone marrow-derived MSCs were susceptible to in vitro lipofectamine mediated TGF-β_(1)gene transfer and that transgene expression persisted for at least 4 weeks.Having successfully combined the existing techniques of tissue engineering with the novel possibilities offered by modern gene transfer technology,an innovative concept,i.e.molecular tissue engineering,are put forward for the first time.As a new branch of tissue engineering,it represents both a new area and an important trend in research.Using this technique,we have a new powerful tool with which:(1)to modify the functional biology of articular tissue repair along defined pathways of growth and differentiation and(2)to affect a better repair of full-thickness articular cartilage defects that occur as a result of injury and osteoarthritis.

Oxysterols as promising small molecules for bone tissue engineering: Systematic review

BACKGROUND Bone tissue engineering is an area of continued interest within orthopaedic surgery,as it promises to create implantable bone substitute materials that obviate the need for autologous bone graft.Recently,oxysterols–oxygenated derivatives of cholesterol-have been proposed as a novel class of osteoinductive small molecules for bone tissue engineering.Here,we present the first systematic review of the in vivo evidence describing the potential therapeutic utility of oxysterols for bone tissue engineering.AIM To systematically review the available literature examining the effect of oxysterols on in vivo bone formation.METHODS We conducted a systematic review of the literature following PRISMA guidelines.Using the PubMed/MEDLINE,Embase,and Web of Science databases,we queried all publications in the English-language literature investigating the effect of oxysterols on in vivo bone formation.Articles were screened for eligibility using PICOS criteria and assessed for potential bias using an expanded version of the SYRCLE Risk of Bias assessment tool.All full-text articles examining the effect of oxysterols on in vivo bone formation were included.Extracted data included:Animal species,surgical/defect model,description of therapeutic and control treatments,and method for assessing bone growth.Primary outcome was fusion rate for spinal fusion models and percent bone regeneration for critical-sized defect models.Data were tabulated and described by both surgical/defect model and oxysterol employed.Additionally,data from all included studies were aggregated to posit the mechanism by which oxysterols may mediate in vivo bone formation.RESULTS Our search identified 267 unique articles,of which 27 underwent full-text review.Thirteen studies(all preclinical)met our inclusion/exclusion criteria.Of the 13 included studies,5 employed spinal fusion models,2 employed critical-sized alveolar defect models,and 6 employed critical-sized calvarial defect models.Based upon SYRCLE criteria,the included studies were found to possess an overall“unclear risk of bias”;54%of studies reported treatment randomization and 38%reported blinding at any level.Overall,seven unique oxysterols were evaluated:20(S)-hydroxycholesterol,22(R)-hydroxycholesterol,22(S)-hydroxycholesterol,Oxy4/Oxy34,Oxy18,Oxy21/Oxy133,and Oxy49.All had statistically significant in vivo osteoinductive properties,with Oxy4/Oxy34,Oxy21/Oxy133,and Oxy49 showing a dose-dependent effect in some cases.In the eight studies that directly compared oxysterols to rhBMP-2-treated animals,similar rates of bone growth occurred in the two groups.Biochemical investigation of these effects suggests that they may be primarily mediated by direct activation of Smoothened in the Hedgehog signaling pathway.CONCLUSION Present preclinical evidence suggests oxysterols significantly augment in vivo bone formation.However,clinical trials are necessary to determine which have the greatest therapeutic potential for orthopaedic surgery patients.

Application of a pre-filled tissue expander for preventing soft tissue incarceration during tibial distraction osteogenesis

BACKGROUND Bone transport and distraction osteogenesis has been widely used to treat bone defects after traumatic surgery,but,skin and soft tissue incarceration can be as high as 27.6%.AIM To investigate the efficacy of inserting a tissue expander to prevent soft tissue incarceration.METHODS Between January 2016 and December 2018,12 patients underwent implantation of a tissue expander in the subcutaneous layer in the vicinity of a tibial defect to maintain the soft tissue in position.A certain amount of normal saline was injected into the tissue expander during surgery and was then gradually extracted to shrink the expander during the course of transport distraction osteogenesis.The tissue expander was removed when the two ends of the tibial defect were close enough.RESULTS In all 12 patients,the expanders remained intact in the subcutaneous layer of the bone defect area during the course of transport distraction osteogenesis.When bone transport was adequate,the expander was removed and the bone transport process was completed.During the whole process,there was no incarceration of skin and soft tissue in the bone defect area.Complications occurred in one patient,who experienced poor wound healing.CONCLUSION The pre-filled expander technique can effectively avoid soft tissue incarceration.The authors’primary success with this method indicates that it may be a valuable tool in the management of incarcerated soft tissue.

中药有效成分结合骨组织工程材料用于骨修复

背景:如何修复骨缺损一直以来是临床难题,中药有效成分在骨修复方面具有良好的生物活性与治疗效果,将中药有效成分与组织工程材料相结合在骨修复领域具有广阔的前景。不同中药有效成分与支架的组合在作用关系方面具有相似之处。目的:搜集常见的中药有效成分与支架材料组合的案例,基于七情配伍的启发将组织工程支架与中药有效成分类比为产生配伍关系的两类中药,以二者的作用关系为纲进行归纳总结。方法:检索1998年1月至2024年1月Pub Med和中国知网数据库中发表的相关文献,英文检索词:“traditional Chinese medicine,Chinese medicine,traditional Chinese medicine monomers,bone defect,bone repair,bone tissue engineering,tissue engineering,scaffold”,中文检索词:“中药,中药有效成分,中药单体,骨组织工程,骨组织工程支架,支架,组织工程,骨缺损,骨修复”,最终纳入88篇文献进行综述分析。结果与结论:(1)组织工程支架材料与中药有效成分各自均在骨修复领域有广泛的运用,二者在成骨方面优势明显但仍有许多缺陷,许多研究致力于将二者制备成复合材料,希望通过二者间的相互作用发挥减毒增效作用。(2)一些药物与材料在成骨、抗菌、促血管生成方面能互相促进,增强原有的效果,受到传统方剂配伍观念的启发,文章将其归纳为“相须”关系,并举实例佐证。(3)一些药物能提高材料的强度,而某些材料能对负载于其上的药物实现缓释控释效果、增加载药量与稳定性,或是进行靶向递送,文章将这种单方面的提升效果归纳为“相使”关系。(4)一些中药与材料搭配使用能减少对方的毒副反应,文章将这种减毒关系归纳为“相畏相杀”。(5)文章得出了一个由七情配伍关系启发、基于作用关系分类的关于中药复合支架的全新视角,将中药传统观念引入组织工程领域,为后续复合支架的研究者提供新的研究思路,并在选材搭配方面提供一定的便利。