New native tissue repair for pelvic organ prolapse:Medium-term outcomes of laparoscopic vaginal stump-round ligament fixation

BACKGROUND Laparoscopic sacrocolpopexy for pelvic organ prolapse(POP)is a new and widely used approach;however,ever since the United States Food and Drug Administration warned against the use of surgical mesh,repairs performed using patients’tissues[i.e.native tissue repair(NTR)]instead of mesh have attracted much attention.At our hospital,laparoscopic sacrocolpopexy(the Shull method)was introduced in 2017.However,patients with more severe POP who have a long vaginal canal and overextended uterosacral ligaments may not be candidates for this procedure.AIM To validate a new NTR treatment for POP,we examined patients undergoing laparoscopic vaginal stump–round ligament fixation(the Kakinuma method).METHODS The study patients were 30 individuals with POP who underwent surgery using the Kakinuma method between January 2020 and December 2021 and who were followed up for>12 mo after surgery.We retrospectively examined surgical outcomes for surgery duration,blood loss,intraoperative complications,and incidence of recurrence.The Kakinuma method involves round ligament suturing and fixation on both sides,effectively lifting the vaginal stump after laparoscopic hysterectomy.RESULTS The patients’mean age was 66.5±9.1(45-82)years,gravidity was 3.1±1.4(2-7),parity was 2.5±0.6(2-4)times,and body mass index was 24.5±3.3(20.9-32.8)kg/m2.According to the POP quantification stage classification,there were 8 patients with stage Ⅱ,11 with stage Ⅲ,and 11 with stage Ⅳ.The mean surgery duration was 113.4±22.6(88-148)min,and the mean blood loss was 26.5±39.7(10-150)mL.There were no perioperative complications.None of the patients exhibited reduced activities of daily living or cognitive impairment after hospital discharge.No cases of POP recurrence were observed 12 mo after the operation.CONCLUSION The Kakinuma method,similar to conventional NTR,may be an effective treatment for POP.

Role of endogenous Schwann cells in tissue repair after spinal cord injury

Schwann cells are glial cells of peripheral nervous system, responsible for axonal myelination and ensheathing, as well as tissue repair following a peripheral nervous system injury. They are one of several cell types that are widely studied and most commonly used for cell transplantation to treat spinal cord injury, due to their intrinsic characteristics including the ability to secrete a variety of neurotrophic factors. This mini review summarizes the recent findings of endogenous Schwann cells after spinal cord injury and discusses their role in tissue repair and axonal regeneration. After spinal cord injury, numerous endogenous Schwann cells migrate into the lesion site from the nerve roots, involving in the construction of newly formed repaired tissue and axonal myelination. These invading Schwann cells also can move a long distance away from the injury site both rostrally and caudally. In addition, Schwann cells can be induced to migrate by minimal insults （such as scar ablation） within the spinal cord and integrate with astrocytes under certain circumstances. More importantly, the host Schwann cells can be induced to migrate into spinal cord by transplantation of different cell types, such as exogenous Schwann cells, olfactory ensheathing cells, and bone marrow-derived stromal stem cells. Migration of endogenous Schwann cells following spinal cord injury is a common natural phenomenon found both in animal and human, and the myelination by Schwann cells has been examined effective in signal conduction electrophysiologically. Therefore, if the inherent properties of endogenous Schwann cells could be developed and utilized, it would offer a new avenue for the restoration of injured spinal cord.

Self-healing hydrogel for tissue repair in the central nervous system

Neurological disorders are diseases of the central and peripheral nervous systems.These disorders include Alzheimer＇s disease,epilepsy,brain tumor,and cerebrovascular diseases（stroke,migraine and other headache disorders,multiple sclerosis,Parkinson＇s disease,and neuroinfections）.

Extracellular matrix based biomaterials for central nervous system tissue repair: the benefits and drawbacks

Functional repair of injured tissue in the adult central nervous system （CNS） still remains a big challenge for current biomed- ical research and its upcoming clinical translation. The axonal regeneration of the adult CNS is generally low, and it is addi- tionally restricted after injury by the presence of inhibitory mol- ecules, generated by the glial scar.

Glycerol solutions of highly concentrated biomineral counter-ions towards water-responsive mineralization: Demonstration on bacterial cellulose and its application in hard tissue repair

Mineralization has found widespread use in the fabrication of composite biomaterials for hard tissue regeneration.The current mineralization processes are mainly carried out in neutral aqueous solutions of biomineral counter-ions(a pair of cation and anion that form the corresponding minerals at certain conditions),which are stable only at very low concentrations.This typically results in inefficient mineralization and weak control over biomineral formation.Here,we find that,in the organic solvent glycerol,a variety of biomineral counter-ions(e.g.,Ca/PO_(4),Ca/CO_(3),Ca/SO_(4),Mg/PO_(4),or Fe/OH)corresponding to distinct biominerals at significantly high concentrations(up to hundreds-fold greater than those of simulated body fluid(SBF))are able to form translucent and stable solutions(mineralizing solution of highly concentrated counter-ions(MSCIs)),and mineralization can be triggered upon them with external solvents(e.g.,water or ethanol).Furthermore,with pristine bacterial cellulose(BC)membrane as a model,we demonstrate an effective and controllable mineralization performance of MSCIs on organic substrates.This approach not only forms the homogeneous biominerals on the BC fibers and in the interspaces,but also provides regulations over mineralization rate,mineral content,phase,and dopants.The resulting mineralized BC membranes(MBCs)exhibit high cytocompatibility and favor the proliferation of rat bone marrow mesenchymal stem cells(rBMSC).Following this,we prepare a mineralized bone suture(MBS)from MBC for non-weight bearing bone fixation,which then is tested on a rabbit median sternotomy model.It shows firm fixation of the rabbit sternum without causing discernible toxicity or inflammatory response.This study,by extending the mineralization to the organic solution system of highly concentrated counter-ions,develops a promising strategy to design and build targeted mineral-based composites.

Therapeutic strategies of three-dimensional stem cell spheroids and organoids for tissue repair and regeneration

Three-dimensional(3D)stem cell culture systems have attracted considerable attention as a way to better mimic the complex interactions between individual cells and the extracellular matrix(ECM)that occur in vivo.Moreover,3D cell culture systems have unique properties that help guide specific functions,growth,and processes of stem cells(e.g.,embryogenesis,morphogenesis,and organogenesis).Thus,3D stem cell culture systems that mimic in vivo environments enable basic research about various tissues and organs.In this review,we focus on the advanced therapeutic applications of stem cell-based 3D culture systems generated using different engineering techniques.Specifically,we summarize the historical advancements of 3D cell culture systems and discuss the therapeutic applications of stem cell-based spheroids and organoids,including engineering techniques for tissue repair and regeneration.

3D bioprinting of cell-laden nano-attapulgite/gelatin methacrylate composite hydrogel scaffolds for bone tissue repair

Bone tissue engineering(BTE)has proven to be a promising strategy for bone defect repair.Due to its excellent biological properties,gelatin methacrylate(GelMA)hydrogels have been used as bioinks for 3D bioprinting in some BTE studies to produce scaffolds for bone regeneration.However,applications for load-bearing defects are limited by poor mechanical properties and a lack of bioactivity.In this study,3D printing technology was used to create nano-attapulgite(nano-ATP)/GelMA composite hydrogels loaded into mouse bone mesenchymal stem cells(BMSCs)and mouse umbilical vein endothelial cells(MUVECs).The bioprintability,physicochemical properties,and mechanical properties were all thoroughly evaluated.Our findings showed that nano-ATP groups outperform the control group in terms of printability,indicating that nano-ATP is beneficial for printability.Additionally,after incorporation with nano-ATP,the mechanical strength of the composite hydrogels was significantly improved,resulting in adequate mechanical properties for bone regeneration.The presence of nano-ATP in the scaffolds has also been stud-ied for cell-material interactions.The findings show that cells within the scaffold not only have high viability but also a clear proclivity to promote osteogenic differentiation of BMSCs.Besides,the MUVECs-loaded composite hydrogels demonstrated increased angiogenic activity.A cranial defect model was also developed to evaluate the bone repair capability of scaffolds loaded with rat BMSCs.According to histo-logical analysis,cell-laden nano-ATP composite hydrogels can effectively im prove bone regeneration and promote angiogenesis.This study demonstrated the potential of nano-ATP for bone tissue engineering,which should also increase the clinical practicality of nano-ATP.

Repair cell first,then regenerate the tissues and organs

Wound healing,tissue repair and regenerative medicine are in great demand,and great achievements in these fields have been made.The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly;however,the basic process of repair at the cell level is often neglected.Because the cell is the basic unit of organism structure and function;cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury.Then,damage to tissues and organs occurs with massive cell damage,apoptosis and even cell death.Thus,how to achieve the aim of perfect repair and regeneration?The basic process of tissue or organ repair and regeneration should involve repair of cells first,then tissues and organs.In this manuscript,it is my consideration about how to repair the cell first,then regenerate the tissues and organs.

Rational design of biodegradable thermoplastic polyurethanes for tissue repair

As a type of elastomeric polymers,non-degradable polyurethanes(PUs)have a long history of being used in clinics,whereas biodegradable PUs have been developed in recent decades,primarily for tissue repair and regeneration.Biodegradable thermoplastic(linear)PUs are soft and elastic polymeric biomaterials with high mechanical strength,which mimics the mechanical properties of soft and elastic tissues.Therefore,biodegradable thermoplastic polyurethanes are promising scaffolding materials for soft and elastic tissue repair and regeneration.Generally,PUs are synthesized by linking three types of changeable blocks:diisocyanates,diols,and chain extenders.Alternating the combination of these three blocks can finely tailor the physio-chemical properties and generate new functional PUs.These PUs have excellent processing flexibilities and can be fabricated into three-dimensional(3D)constructs using conventional and/or advanced technologies,which is a great advantage compared with cross-linked thermoset elastomers.Additionally,they can be combined with biomolecules to incorporate desired bioactivities to broaden their biomedical applications.In this review,we comprehensively summarized the synthesis,structures,and properties of biodegradable thermoplastic PUs,and introduced their multiple applications in tissue repair and regeneration.A whole picture of their design and applications along with discussions and perspectives of future directions would provide theoretical and technical supports to inspire new PU development and novel applications.

A new hemostatic agent composed of Zn^(2+)-enriched Ca^(2+)alginate activates vascular endothelial cells in vitro and promotes tissue repair in vivo

To control capillary bleeding, surgeons may use absorbable hemostatic agents, such as Surgicel® and TachoSil®. Due to their slow resorption, their persistence in situ can have a negative impact on tissue repair in the resected organ. To avoid complications and obtain a hemostatic agent that promotes tissue repair, a zinc-supplemented calcium alginate compress was developed: HEMO-IONIC®. This compress is non-absorbable and is therefore removed once hemostasis has been achieved. After demonstrating the hemostatic efficacy and stability of the blood clot obtained with HEMO-IONIC, the impact of Surgicel, TachoSil, and HEMO-IONIC on cell activation and tissue repair were compared (i) in vitro on endothelial cells, which are essential to tissue repair, and (ii) in vivo in a mouse skin excision model. In vitro, only HEMO-IONIC maintained the phenotypic and functional properties of endothelial cells and induced their migration. In comparison, Surgicel was found to be highly cytotoxic, and TachoSil inhibited endothelial cell migration. In vivo, only HEMO-IONIC increased angiogenesis, the recruitment of cells essential to tissue repair (macrophages, fibroblasts, and epithelial cells), and accelerated maturation of the extracellular matrix. These results demonstrate that a zinc-supplemented calcium alginate, HEMO-IONIC, applied for 10 min at the end of surgery and then removed has a long-term positive effect on all phases of tissue repair.

Stem cell niches and endogenous electric fields in tissue repair

Adult stem cells are responsible for homeostasis and repair of many tissues.Endogenous adult stem cells reside in certain regions of organs,known as the stem cell niche,which is recognized to have an important role in regulating tissue maintenance and repair.In wound healing and tissue repair,stem cells are mobilized and recruited to the site of wound,and participate in the repair process.Many regulatory factors are involved in the stem cell-based repair process,including stem cell niches and endogenous wound electric fields,which are present at wound tissues and proved to be important in guiding wound healing.Here we briefly review the role of stem cell niches and endogenous electric fields in tissue repair,and hypothesize that endogenous electric fields become part of stem cell niche in the wound site.

Advances in mesenchymal stem cell-mediated tissue repair of lung injury

The repair of lung injury has always been a fundamental problem in the treatment of acute and chronic lung diseases,and more effective treatment approaches have been sought.Regenerative medicine,which gradually repairs impaired tissue and improves lung function,has been increasingly applied in the field of acute and chronic respiratory diseases.

Decellularized small intestine submucosa/polylactic-co-glycolic acid composite scaffold for potential application in hypopharyngeal and cervical esophageal tissue repair

There has been an increase in the incidence of hypopharyngeal and cervical esophageal cancer worldwide,and hence growing needs for hypopharyngeal and cervical esophageal tissue repair.This work produced a bi-layer composite scaffold with decellularized small intestine submucosa and polylactic-co-glycolic acid,which resembled the layered architectures of its intended tissues.The decellularized small intestine submucosa contained minimal residual DNA(52.5±61.2 ng/mg)and the composite scaffold exhibited satisfactory mechanical properties(a tensile modulus of 21.1±64.8 MPa,an ultimate tensile strength of 14.0±62.9MPa and a failure strain of 26.9±65.1%).The interactions between cells and the respective layers of the scaffold were characterized by CCK-8 assays,immunostaining and Western blotting.Desirable cell proliferation and phenotypic behaviors were observed.These results have provided an important basis for the next-step in vivo studies of the scaffold,and bode well for its future clinical applications.

Polyhydroxyalkanoates in tissue repair and regeneration

Developing advanced biocompatibility materials is of critical importance in biomedical engineering.Polyhydrox-yalkanoates(PHA),being famous for its flexible mechanical properties,thermal properties,biocompatibility,and biodegradability,has been widely used in wound dressings,artificial blood vessels,heart valves,nerve conduits,bone and cartilage scaffolds,surgical sutures,and other fields.However,reports on the application of PHA in tissue repair and regeneration are often lacking in systematics.Here,a comprehensive and in-depth perception of the performance advantages and application value of PHA is provided.In this review,the following applications of PHA in biomedical engineering are covered:i)soft tissue,ii)organ tissue,iii)vascular tissue,iv)heart valve tissue,v)nerve conduit tissue,vi)bone tissue,vii)cartilage tissue and viii)others.Finally,an outlook on the future research directions and challenges of PHA is presented.

Oscillating field stimulation promotes neurogenesis of neural stem cells through miR-124/Tal1 axis to repair spinal cord injury in rats

Spinal cord injury often leads to severe motor and sensory deficits,and prognosis using the currently available therapies remains poor.Therefore,we aimed to explore a novel therapeutic approach for improving the prognosis of spinal cord injury.In this study,we implanted oscillating field stimulation devices and transplanted neural stem cells into the thoracic region(T9–T10)of rats with a spinal cord contusion.Basso-Beattie-Bresnahan scoring revealed that oscillating field stimulation combined with neural stem cells transplantation promoted motor function recovery following spinal cord injury.In addition,we investigated the regulation of oscillating field stimulation on the miR-124/Tal1 axis in neural stem cells.Transfection of lentivirus was performed to investigate the role of Tal1 in neurogenesis of neural stem cells induced by oscillating field stimulation.Quantitative reverse transcription-polymerase chain reaction,immunofluorescence and western blotting showed that oscillating field stimulation promoted neurogenesis of neural stem cells in vitro and in vivo.Hematoxylin and eosin staining showed that oscillating field stimulation combined with neural stem cells transplantation alleviated cavities formation after spinal cord injury.Taking the results together,we concluded that oscillating field stimulation decreased miR-124 expression and increased Tal1 content,thereby promoting the neurogenesis of neural stem cells.The combination of oscillating field stimulation and neural stem cells transplantation improved neurogenesis,and thereby promoted structural and functional recovery after spinal cord injury.

Repairing peripheral nerve injury using tissue engineering techniques

Each year approximately 360,000 people in the United States suffer a peripheral nerve injury （PNI）, which is a leading source of lifelong disability （Kelsey et al., 1997; Noble et al., 1998）. The most frequent cause of PNIs is motor vehicle accidents, while gunshot wounds, stabbings, and birth trauma are also common factors. Patients suffering from disabilities as a result of their PNIs are also burdensome to the healthcare system, with aver- age hospital stays of 28 days each year （Kelsey et al., 1997; Noble et al., 1998）.

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.

Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration

Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately byAchilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment （kinesitherapy）. Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7-21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy.

A Systematic Review of Animal and Clinical Studies on the Use of Scaffolds for Urethral Repair

Replacing urethral tissue with functional scaffolds has been one of the challenging problems in the field of urethra reconstruction or repair over the last several decades. Various scaffold materials have been used in animal studies, but clinical studies on use of scaffolds for urethral repair are scarce. The aim of this study was to review recent animal and clinical studies on the use of different scaffolds for urethral repair, and to evaluate these scaffolds based on the evidence from these studies. Pub Med and OVID databases were searched to identify relevant studies, in conjunction with further manual search. Studies that met the inclusion criteria were systematically evaluated. Of 555 identified studies, 38 were included for analysis. It was found that in both animal and clinical studies, scaffolds seeded with cells were used for repair of large segmental defects of the urethra, such as in tubular urethroplasty. When the defect area was small, cell-free scaffolds were more likely to be applied. A lot of pre-clinical and limited clinical evidence showed that natural or artificial materials could be used as scaffolds for urethral repair. Urinary tissue engineering is still in the immature stage, and the safety, efficacy, cost-effectiveness of the scaffolds are needed for further study.

Current status and prospects of basic research and clinical application of mesenchymal stem cells in acute respiratory distress syndrome

Acute respiratory distress syndrome(ARDS)is a common and clinically devastating disease that causes respiratory failure.Morbidity and mortality of patients in intensive care units are stubbornly high,and various complications severely affect the quality of life of survivors.The pathophysiology of ARDS includes increased alveolar–capillary membrane permeability,an influx of protein-rich pulmonary edema fluid,and surfactant dysfunction leading to severe hypoxemia.At present,the main treatment for ARDS is mechanical treatment combined with diuretics to reduce pulmonary edema,which primarily improves symptoms,but the prognosis of patients with ARDS is still very poor.Mesenchymal stem cells(MSCs)are stromal cells that possess the capacity to self-renew and also exhibit multilineage differentiation.MSCs can be isolated from a variety of tissues,such as the umbilical cord,endometrial polyps,menstrual blood,bone marrow,and adipose tissues.Studies have confirmed the critical healing and immunomodulatory properties of MSCs in the treatment of a variety of diseases.Recently,the potential of stem cells in treating ARDS has been explored via basic research and clinical trials.The efficacy of MSCs has been shown in a variety of in vivo models of ARDS,reducing bacterial pneumonia and ischemia-reperfusion injury while promoting the repair of ventilator-induced lung injury.This article reviews the current basic research findings and clinical applications of MSCs in the treatment of ARDS in order to emphasize the clinical prospects of MSCs.