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Recapitulation of growth factor-enriched microenvironment via BMP receptor activating hydrogel

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Bioactive Materials 2023年第2期20卷 638-650页

作者： Qinghao Zhang Yuanda liu Jie Li Jing Wang changsheng liu Material Science and Engineering School East China University of Science and TechnologyShanghai200237PR China Engineering Research Center for Biomedical Materials of Ministry of Education East China University of Science and TechnologyShanghai200237PR China Key Laboratory for Ultrafine Materials of Ministry of Education East China University of Science and TechnologyShanghai200237PR China Frontiers Science Center for Materiobiology and Dynamic Chemistry East China University of Science and TechnologyMeilong Road 130Shanghai200237PR China The State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai200237PR China

Exposure to a growth factor abundant milieu has remarkable regenerative and rejuvenating effects on organ diseases,tissue damage,and regeneration,including skeletal system defects and bone regeneration.Although the introduction of candidate growth factors into relevant fields has been reported,their regenerative effects remain unsatisfactory,mainly because of the experimental challenges with limited types of growth factors,elusive dosage adjustment,and asynchronous stem cell activation with cytokine secretion.Here,an innovative hydrogel recapitulating a growth factor-enriched microenvironment(GEM)for regenerative advantage,is reported.This sulfated hydrogel includes bone morphogenetic protein-2(BMP-2),an essential growth factor in osteogenesis,to direct mesenchymal stem cell(MSC)differentiation,stimulate cell proliferation,and improve bone formation.The semi-synthetic hydrogel,sulfonated gelatin(S-Gelatin),can amplify BMP-2 signaling in mouse MSCs by enhancing the binding between BMP-2 and BMP-2 type II receptors(BMPR2),which are located on MSC nuclei and activated by the hydrogel.Importantly,the dramatically improved cytokine secretion of MSCs throughout regeneration confirms the growth factor-acquiring potential of S-Gelatin/rhBMP-2 hydrogel,leading to the vascularization enhancement.These findings provide a new strategy to achieve an in situ GEM and accelerated bone regeneration by amplifying the regenerative capacity of rhBMP-2 and capturing endogenous growth factors.

关键词： BMP-2 Sulfonated acids BMP receptor Activation Endogenous growth factor acquisition Bone regeneration

Decellularized extracellular matrix scaffolds:Recent trends and emerging strategies in tissue engineering

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Bioactive Materials 2022年第4期7卷 15-31页

作者： Xuewei Zhang Xi Chen Hua Hong Rubei Hu Jiashang liu changsheng liu Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic ChemistryEngineering Research Center for Biomaterials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237PR China

The application of scaffolding materials is believed to hold enormous potential for tissue regeneration.Despite the widespread application and rapid advance of several tissue-engineered scaffolds such as natural and synthetic polymer-based scaffolds,they have limited repair capacity due to the difficulties in overcoming the immunogenicity,simulating in-vivo microenvironment,and performing mechanical or biochemical properties similar to native organs/tissues.Fortunately,the emergence of decellularized extracellular matrix(dECM)scaffolds provides an attractive way to overcome these hurdles,which mimic an optimal non-immune environment with native three-dimensional structures and various bioactive components.The consequent cell-seeded construct based on dECM scaffolds,especially stem cell-recellularized construct,is considered an ideal choice for regenerating functional organs/tissues.Herein,we review recent developments in dECM scaffolds and put forward perspectives accordingly,with particular focus on the concept and fabrication of decellularized scaffolds,as well as the application of decellularized scaffolds and their combinations with stem cells(recellularized scaffolds)in tissue engineering,including skin,bone,nerve,heart,along with lung,liver and kidney.

关键词： Decellularization ECM 3D scaffolds Tissue regeneration Recellularization

Construction of developmentally inspired periosteum-like tissue for bone regeneration

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Bone Research 2022年第1期10卷 81-94页

作者： Kai Dai Shunshu Deng Yuanman Yu Fuwei Zhu Jing Wang changsheng liu State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghaiP.R.China Engineering Research Center for Biomedical Materials of Ministry of Education East China University of Science and TechnologyShanghaiP.R.China Key Laboratory for Ultrafine Materials of Ministry of Education East China University of Science and TechnologyShanghaiP.R.China Frontiers Science Center for Materiobiology and Dynamic Chemistry East China University of Science and TechnologyShanghaiP.R.China

The periosteum, a highly vascularized thin tissue, has excellent osteogenic and bone regenerative abilities. The generation of periosteum-mimicking tissue has become a novel strategy for bone defect repair and regeneration, especially in critical-sized bone defects caused by trauma and bone tumor resection. Here, we utilized a bone morphogenetic protein-2(BMP-2)-loaded scaffold to create periosteum-like tissue(PT) in vivo, mimicking the mesenchymal condensation during native long bone development. We found that BMP-2-induced endochondral ossification plays an indispensable role in the construction of PTs. Moreover, we confirmed that BMP-2-induced PTs exhibit a similar architecture to the periosteum and harbor abundant functional periosteum-like tissue-derived cells(PTDCs), blood vessels, and osteochondral progenitor cells. Interestingly, we found that the addition of chondroitin sulfate(CS), an essential component of the extracellular matrix(ECM), could further increase the abundance and enhance the function of recruited PTDCs from the PTs and finally increase the regenerative capacity of the PTs in autologous transplantation assays, even in old mice. This novel biomimetic strategy for generating PT through in vivo endochondral ossification deserves further clinical translation.

关键词： sized utilized finally

Harnessing strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns

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Bioactive Materials 2023年第10期28卷 243-254页

作者： Yixin Cai Kangli Chen changsheng liu Xue Qu Key Laboratory for Ultrafine Materials of Ministry of Education School of Material Science and EngineeringFrontiers Science Center for Materiobiology and Dynamic ChemistryEast China University of Science and TechnologyShanghai200237China Wenzhou Institute of Shanghai University Wenzhou325000China Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism Shanghai200237China

Diabetic wound is a great threat to patient’s health and lives.The refractory diabetic wound shows spatial inflammation patterns,in which the early-wound pattern depicts a deprived acute inflammatory response,and the long-term non-healing wound pattern delineates an excessive and persistent inflammation due to the delayed immune cell infiltration in a positive feedback loop.In this work,we give points to some strategies to normalize the dysregulated immune process based on the spatial inflammation pattern differences in diabetic wound healing.First of all,inhibiting inflammatory response to avoid subsequent persistent and excessive immune infiltration for the early diabetic wound is proposed.However,diabetic wounds are unperceptive trauma that makes patients miss the best treatment time.Therefore,we also introduce two strategies for the long-term non-healing diabetic wound.One strategy is about changing chronic wounds to acute ones,which aims to rejuvenate M1 macrophages in diabetic wounds and make spontaneous M2 polarization possible.To activate the controllable proinflammatory response,western medicine delivers proinflammatory molecules while traditional Chinese medicine develops“wound-pus promoting granulation tissue growth theory”.Another strategy to solve long-term non-healing wounds is seeking switches that target M1/M2 transition directly.These investigations draw a map that delineates strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns systematically.

关键词： Diabetic wound Spatial inflammation pattern M1/M2 transition Biomaterials

Fabrication and evaluation of a BMP-2/dexamethasone co-loaded gelatin sponge scaffold for rapid bone regeneration

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Regenerative Biomaterials 2022年第1期9卷 303-313页

作者： Qi Gan Hao Pan Wenjing Zhang Yuan Yuan Jiangchao Qian changsheng liu Key Laboratory for Ultrafine Materials of Ministry of Education East China University of Science and TechnologyShanghai 200237PR China The State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237PR China Engineering Research Center for Biomedical Materials of the Ministry of Education East China University of Science and TechnologyShanghai 200237PR China Frontiers Science Center for Materiobiology and Dynamic Chemistry East China University of Science and TechnologyShanghai 200237PR China

Improving the osteogenic activity of BMP-2 in vivo has significant clinical application value.In this research,we use a clinical gelatin sponge scaffold loaded with BMP-2 and dexamethasone(Dex)to evaluate the osteogenic activity of dual drugs via ectopic osteogenesis in vivo.We also investigate the mechanism of osteogenesis induced by BMP-2 and Dex with C2C12,a multipotent muscle-derived progenitor cell.The results show that the gelatin scaffold with Dex and BMP-2 can significantly accelerate osteogenesis in vivo.It is indicated that compared with the BMP-2 or Dex alone,100nM of Dex can dramatically enhance the BMP-2-induced alkaline phosphatase activity(ALP),ALP mRNA expression and mineralization.Further studies show that 100nM of Dex can maintain the secondary structure of BMP-2 and facilitate recognition of BMP-2 with its receptors on the surface of C2C12 cells.We also find that in C2C12,Dex has no obvious effect on the BMP-2-induced Smad1/5/8 protein expression and the STAT3-dependent pathway,but Runx2-dependent pathway is involved in the Dex-stimulated osteoblast differentiation of BMP-2 both in vitro and in vivo.Based on these results,a potential mechanism model about the synergistic osteoinductive effect of Dex and BMP-2 in C2C12 cells via Runx2 activation is proposed.This may provide a theoretical basis for the pre-clinical application of Dex and BMP-2 for bone regeneration.

关键词： BMP-2 dexamethasone Runx2 pre-clinical bone regeneration

Decellularized extracellular matrix and mesenchymal stem cells promote recovery in traumatic brain injury by synergistically enhancing neurogenesis and attenuating neuroinflammation

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Journal of Materials Science & Technology 2023年第7期138卷 17-28页

作者： Xuewei Zhang Bixue Wang Hua Hong Ying Wang Jiashang liu changsheng liu Xi Chen Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic ChemistryEngineering Research Center for Biomaterials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237China

Damaged neurons and harsh microenvironments contribute to the injury cascades following traumatic brain injury(TBI).Mesenchymal stem cell(MSC)therapy is considered a viable choice for brain in-jury treatment;however,its clinical use is hindered by limited engraftment,low survival ratio,and uncontrolled differentiation.Herein,the decellularized brain extracellular matrix(dBECM)was prepared through a new method as a delivery system for MSCs.dBECM-based hydrogel with favorable biochem-ical and biomechanical features provides a microenvironment for MSCs in nerve repair.The MSCs-encapsulated dBECM-based hydrogel is shown to improve neuron compensation and structural regen-eration,alleviate neuroinflammation,and promote M1-to-M2 polarization of microglia.Our results first demonstrate that the combination of dBECM and MSCs is a critical vehicle to promote TBI repair from neurogenesis and immunoregulation,showing promise for the physiological recovery of neurogenic dis-eases and injuries.

关键词： ECM Stem cells Brain injury Neurogenesis Neuroinflammation

Repurpose dasatinib and quercetin:Targeting senescent cells ameliorates postmenopausal osteoporosis and rejuvenates bone regeneration

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Bioactive Materials 2023年第7期25卷 13-28页

作者： Ying Wang Lingbin Che Xi Chen Zirui He Dianwen Song Yuan Yuan changsheng liu Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic ChemistryEngineering Research Center for Biomaterials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237PR China Department of Orthopedics Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai200080China

Clinical therapies developed for estrogen-deficiency-driven postmenopausal osteoporosis(PMO)and related diseases,such as bone degeneration,show multiple adverse effects nowadays.Targeting senescent cells(SnCs)and the consequent senescence-associated secretory phenotype(SASP)with a combination of dasatinib and quercetin(DQ)is a recently developed novel therapy for multiple age-related diseases.Herein,we found that estrogen deficiency induced-bone loss was attributed to a pro-inflammatory microenvironment with SASP secretions and accelerated SnC accumulation,especially senescent mesenchymal stem cells(MSCs)characterized by exhaustion and dysfunction in middle aged rats.Systematically targeting SnCs with DQ strikingly ameliorated PMO and restored MSC function.Local administration of DQ and bone morphogenetic protein 2(BMP2)in combination promoted osteogenic differentiation of MSCs and rejuvenated osteoporotic bone regeneration.Our results repurposed DQ as an attractive therapy for treating PMO and related diseases.

关键词： Postmenopausal osteoporosis Dasatinib and quercetin Senescent cells Mesenchymal stem cell Bone regeneration

A comprehensive review of bioactive compounds and processing technology of sesame seed

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Oil Crop Science 2022年第2期7卷 88-94页

作者： Xuan Ma Zhi Wang Chang Zheng changsheng liu Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences Oil Crops and Lipids Process Technology National&Local Joint Engineering LaboratoryKey Laboratory of Oilseeds ProcessingMinistry of Agriculture and Rural AffairsHubei Key Laboratory of Lipid Chemistry and NutritionWuhan430062China

Sesame seeds are promulgated as traditional high-quality edible oil crops,rich in lipid(40–65%),protein(19–35%),and bioactive compounds.The review starts with bioactive components(fatty acid,tocopherol,phytosterol,sesamin,sesamolin,and sesamol)of sesame seeds.It considers processing techniques for extracting oil(aqueous extraction and pressing)from seeds.Novel technologies,such as enzyme-assisted aqueous,supercritical CO_(2),and microwave-assisted solvent extraction,are also discussed.The methods of utilization of sesame seed cake are also analyzed.In the future,the processing technology of sesame seed will be further developed in the direction of improving comprehensive utilization rate to meet new consumption demand.

关键词： Sesame seed Bioactive compound Nutritional properties Processing technology By-product

A biomimetic and bioactive scaffold with intelligently pulsatile teriparatide delivery for local and systemic osteoporosis regeneration

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生物活性材料(英文) 2023年第1期19卷 75-87页

作者： Lingbin Che Ying Wang Dongyong Sha Guangyi Li Ziheng Wei changsheng liu Yuan Yuan Dianwen Song Department of Orthopedics Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai200080PR China Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry and School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237PR China Shanghai Advanced Research Institute Chinese Academy of SciencesShanghai201210PR China

Osteoporosis is one of the most disabling consequences of aging,osteoporotic fractures and higher risk of the subsequent fractures leading to substantial disability and deaths,indicating both local fractures healing and the early anti-osteoporosis therapy are of great significance.Teriparatide is strong bone formation promoter effective in treating osteoporosis,while side effects limit clinical applications.Traditional drug delivery is lack of sensitive and short-term release,finding a new non-invasive and easily controllable drug delivery to not only repair the local fractures but also improve total bone mass has remained a great challenge.Thus,bioinspired by the natural bone components,we develop appropriate interactions between inorganic biological scaffolds and organic drug molecules,achieving both loaded with the teriparatide in the scaffold and capable of releasing on demand.Herein,biomimetic bone microstructure of mesoporous bioglass,a near-infrared ray triggered switch,thermosensitive liposomes based on a valve,and polydopamine coated as a heater is developed rationally for osteoporotic bone regeneration.Teriparatide is pulsatile released from intelligent delivery,not only rejuvenating osteoporotic bone defect,but also presenting strong systemic anti-osteoporosis therapy.This biomimetic bone carrying novel drug delivery platform is well worth expecting to be a new promising strategy and clinically commercialized to help patients survive from the osteoporotic fracture.

关键词： Precise pulsatile release Teriparatide Smart delivery Osteoporotic bone regeneration