Biologic Scaffold Materials Research Articles

FDG Localization in Acellular Dermal Matrix, a Potential Cause of Nonpernicious Uptake Following Breast Reconstruction Surgery.

A 47-year-old woman with invasive lobular carcinoma of the left breast underwent prophylactic double mastectomy which also incidentally revealed follicular lymphoma of the right breast. Reconstruction was achieved with bilateral silicone implants and acellular dermal matrix (ADM), a biological scaffold material providing mechanical support. Twelve days thereafter, staging PET/CT demonstrated symmetric moderate FDG uptake corresponding to location of the ADM slings, suspected to reflect cellular engraftment onto the ADM and confirmed by near-complete resolution at 3-month follow-up study. FDG uptake related to ADM should be recognized as reflecting expected cellular incorporation into the matrix, rather than recurrent tumor or infection.

Advances in extracellular vesicle-based combination therapies for spinal cord injury.

Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits. The currently available treatments involve surgical, medical, and rehabilitative strategies. However, none of these techniques can markedly reverse neurological deficits. Recently, extracellular vesicles from various cell sources have been applied to different models of spinal cord injury, thereby generating new cell-free therapies for the treatment of spinal cord injury. However, the use of extracellular vesicles alone is still associated with some notable shortcomings, such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons. Therefore, this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury, including the combination of extracellular vesicles with nanoparticles, exogenous drugs and/or biological scaffold materials, which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles. We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.

An Electroconductive Hydrogel Scaffold with Injectability and Biodegradability to Manipulate Neural Stem Cells for Enhancing Spinal Cord Injury Repair

Spinal cord injury (SCI) generally leads to long-term functional deficits and is difficult to repair spontaneously. Many biological scaffold materials and stem cell treatment strategies have been explored, but very little research focused on the method of combining exogenous neural stem cells (NSCs) with a biodegradable conductive hydrogel scaffold. Here, a NSC loaded conductive hydrogel scaffold (named ICH/NSCs) was assembled by amino-modified gelatin (NH2-Gelatin) and aniline tetramer grafted oxidized hyaluronic acid (AT-OHA). Desirably, the well-conducting ICH/NSCs can be simply injected into the target site of SCI for establishing a good electrical signal pathway of cells, and the proper degradation cycle facilitates new nerve growth. In vitro experiments indicated that the inherent electroactive microenvironment of the hydrogel could better manipulate the differentiation of NSCs into neurons and inhibit the formation of glial cells and scars. Collectively, the ICH/NSC scaffold has successfully stimulated the recovery of SCI and may provide a promising treatment strategy for SCI repair.

Porcine Small Intestinal Submucosa Alters the Biochemical Properties of Wound Healing: A Narrative Review.

Among the many biological scaffold materials currently available for clinical use, the small intestinal submucosa (SIS) is an effective material for wound healing. SIS contains numerous active forms of extracellular matrix that support angiogenesis, cell migration, and proliferation, providing growth factors involved in signaling for tissue formation and assisting wound healing. SIS not only serves as a bioscaffold for cell migration and differentiation, but also restores the impaired dynamic reciprocity between cells and the extracellular matrix, ultimately driving wound healing. Here, we review the evidence on how SIS can shift the biochemical balance in a wound from chronic to an acute state.

The improvement of periodontal tissue regeneration using a 3D-printed carbon nanotube/chitosan/sodium alginate composite scaffold.

Periodontal disease is a common disease in the oral field, and many researchers are studying periodontal disease and try to find some biological scaffold materials to make periodontal tissue regenerative. In this study, we attempted to construct a carbon nanotube/chitosan/sodium alginate (CNT/CS/AL) ternary composite hydrogel and then prepare porous scaffold by 3D printing technology. Subsequently, characterizing the materials and testing the mechanical properties of the scaffold. Additionally, its effect on the proliferation of human periodontal ligament cells (hPDLCs) and its antibacterial effect on Porphyromonas gingivalis were detected. We found that CNT/CS/AL porous composite scaffolds with uniform pores could be successfully prepared. Moreover, with increasing CNT concentration, the degradation rate and the swelling degree of scaffold showed a downward trend. The compressive strength test indicated the elastic modulus of composite scaffolds ranged from 18 to 80 kPa, and 1% CNT/CS/AL group had the highest quantitative value. Subsequently, cell experiments showed that the CNT/CS/AL scaffold had good biocompatibility and could promote the proliferation of hPDLCs. Among 0.1%-1% CNT/CS/AL groups, the biocompatibility of 0.5% CNT/CS/AL scaffold performed best. Meanwhile, in vitro antibacterial experiments showed that the CNT/CS/AL scaffold had a certain bacteriostatic effect on P. gingivalis. When the concentration of CNT was more than 0.5%, the antimicrobial activity of composite scaffold was significantly promoted, and about 30% bacteria were inactivated. In conclusion, this 3D-printed CNT/CS/AL composite scaffold, with good material properties, biocompatibility and bacteriostatic activity, may be used for periodontal tissue regeneration, providing a new avenue for the treatment of periodontal disease.

Low-Stiffness Hydrogels Promote Peripheral Nerve Regeneration Through the Rapid Release of Exosomes.

A hydrogel system loaded with mesenchymal stem cell–derived exosome (MSC-Exos) is an attractive new tool for tissue regeneration. However, the effect of the stiffness of exosome-loaded hydrogels on tissue regeneration is unclear. Here, the role of exosome-loaded hydrogel stiffness, during the regeneration of injured nerves, was assessed in vivo. The results showed that the photocrosslinkable hyaluronic acid methacrylate hydrogel stiffness plays an important role in repairing nerve injury. Compared with the stiff hydrogels loaded with exosomes, soft hydrogels loaded with exosomes showed better repair of injured peripheral nerves. The soft hydrogel promoted nerve repair by quickly releasing exosomes to inhibit the infiltration of macrophages and the expression of the proinflammatory factors IL-1β and TNF-α in injured nerves. Our work revealed that exosome-loaded hydrogel stiffness plays an important role in tissue regeneration by regulating exosome release behavior and provided important clues for the clinical application of biological scaffold materials.

Osteogenic differentiation of human dental pulp stem cells in decellularised adipose tissue solid foams.

3D cell culture systems based on biological scaffold materials obtainable from both animal and human tissues constitute very interesting tools for cell therapy and personalised medicine applications. The white adipose tissue (AT) extracellular matrix (ECM) is a very promising biomaterial for tissue engineering due to its easy accessibility, malleability and proven biological activity. In the present study, human dental pulp stem cells (hDPSCs) were combined in vitro with ECM scaffolds from porcine and human decellularised adipose tissues (pDAT, hDAT) processed as 3D solid foams, to investigate their effects on the osteogenic differentiation capacity and bone matrix production of hDPSCs, compared to single-protein-based 3D solid foams of collagen type I and conventional 2D tissue-culture-treated polystyrene plates. pDAT solid foams supported the osteogenic differentiation of hDPSCs to similar levels to collagen type I, as assessed by alkaline phosphatase and alizarin red stainings, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and osteocalcin/bone gamma-carboxyglutamate protein (BGLAP) immunostaining. Interestingly, hDAT solid foams showed a markedly lower capacity to sustain hDPSC osteogenic differentiation and matrix calcification and a higher capacity to support adipogenesis, as assessed by RT-qPCR and oil red O staining. White ATs from both human and porcine origins are relatively abundant and available sources of raw material to obtain high quality ECM-derived biomedical products. These biomaterials could have promising applications in tissue engineering and personalised clinical therapy for the healing and regeneration of lesions involving not only a loss of calcified bone but also its associated soft non-calcified tissues.

Immunomodulatory matrix-bound nanovesicles mitigate acute and chronic pristane-induced rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and destruction of synovial joints affecting ~7.5 million people worldwide. Disease pathology is driven by an imbalance in the ratio of pro-inflammatory vs. anti-inflammatory immune cells, especially macrophages. Modulation of macrophage phenotype, specifically an M1 to M2, pro- to anti-inflammatory transition, can be induced by biologic scaffold materials composed of extracellular matrix (ECM). The ECM-based immunomodulatory effect is thought to be mediated in part through recently identified matrix-bound nanovesicles (MBV) embedded within ECM. Isolated MBV was delivered via intravenous (i.v.) or peri-articular (p.a.) injection to rats with pristane-induced arthritis (PIA). The results of MBV administration were compared to intraperitoneal (i.p.) administration of methotrexate (MTX), the clinical standard of care. Relative to the diseased animals, i.p. MTX, i.v. MBV, and p.a. MBV reduced arthritis scores in both acute and chronic pristane-induced arthritis, decreased synovial inflammation, decreased adverse joint remodeling, and reduced the ratio of synovial and splenic M1 to M2 macrophages (p < 0.05). Both p.a. and i.v. MBV reduced the serum concentration of RA and PIA biomarkers CXCL10 and MCP-3 in the acute and chronic phases of disease (p < 0.05). Flow-cytometry revealed the presence of a systemic CD43hi/His48lo/CD206+, immunoregulatory monocyte population unique to p.a. and i.v. MBV treatment associated with disease resolution. The results show that the therapeutic efficacy of MBV is equal to that of MTX for the management of acute and chronic pristane-induced arthritis and, further, this effect is associated with modulation of local synovial macrophages and systemic myeloid populations.

Recent advancement of decellularization extracellular matrix for tissue engineering and biomedical application

Decellularized extracellular matrixs (dECMs) derived from organs and tissues have emerged as a promising tool, as they encompass the characteristics of an ideal tissue scaffold: complex composition, vascular networks and unique tissue-specific architecture. Consequently, their use has propagated throughout tissue engineering and regenerative medicine. dECM can be easily obtained from various tissues/organs by appropriate decellularization protocolsand is entitled to provide necessary cues to cells homing. In this review, we describe the decellularization and sterilization methods that are commonly used in recent research, the effects of these methods upon biologic scaffold material are discussed. Also, we summarize the recent developments of recellularization and vascularization techniques in regeneration medicine. Additionally, dECM preservation methods is mentioned, which provides the basis for the establishment of organ bank. Biomedical applications and the status of current research developments relating to dECM biomaterials are outlined, including transplantation in vivo, disease models and drug screening, organoid, 3D bioprinting, tissue reconstruction and rehabilitation and cell transplantation and culture. Finally, critical challenges and future developing technologies are discussed. With the development of tissue engineering and regenerative medicine, dECM will have broader applications in the field of biomedicine in the near future.

Renal Regeneration: The Role of Extracellular Matrix and Current ECM-Based Tissue Engineered Strategies.

Natural extracellular matrices (ECM) are currently being studied as an alternative source for organ transplantation or as new solutions to treat kidney injuries, which can evolve to end-stage renal disease, a life devastating condition. This paper provides an overview on the current knowledge in kidney ECM and its usefulness on future investigations. The composition and structure of kidney ECM is herein associated with its intrinsic capacity of remodeling and repair after insult. Moreover, it provides a deeper insight on altered ECM components during disease. The use of decellularized kidney matrices is discussed in the second part of the review, with emphasis on how these matrices contribute to tissue-specific differentiation of embryonic, pluripotent, and other stem cells. The evolution on the field toward different uses of xenogeneic ECM as a biological scaffold material is discussed, namely the major outcomes on whole kidney recellularization and its in vivo implantation. At last, the recent literature on the use of processed kidney decellularized ECM to produce diverse biomaterial substrates, such as hydrogels, membranes, and bioinks are reviewed, with emphasis on future perspectives of its translation into the clinic.

3D bioprinting and microscale organization of vascularized tissue constructs using collagen-based bioink.

Bioprinting three-dimensional (3D) tissue equivalents have progressed tremendously over the last decade. 3D bioprinting is currently being employed to develop larger and more physiologic tissues, and it is of particular interest to generate vasculature in biofabricated tissues to aid better perfusion and transport of nutrition. Having an advantage over manual culture systems by bringing together biological scaffold materials and cells in precise 3D spatial orientation, bioprinting could assist in placing endothelial cells in specific spatial locations within a 3D matrix to promote vessel formation at these predefined areas. Hence, in the present study, we investigated the use of bioprinting to generate tissue-level capillary-like networks in biofabricated tissue constructs. First, we developed a bioink using collagen type-1 supplemented with xanthan gum (XG) as a thickening agent. Using a commercial extrusion-based multi-head bioprinter and collagen-XG bioink, the component cells were spatially assembled, wherein the endothelial cells were bioprinted in a lattice pattern and sandwiched between bioprinted fibroblasts layers. 3D bioprinted constructs thus generated were stable, and maintained structural shape and form. Post-print culture of the bioprinted tissues resulted in endothelial sprouting and formation of interconnected capillary-like networks within the lattice pattern and between the fibroblast layers. Bioprinter-assisted spatial placement of endothelial cells resulted in fabrication of patterned prevascularized constructs that enable potential regenerative applications in the future.

Special Issue: Application of Extracellular Matrix in Regenerative Medicine

The present Special Issue comprises a collection of articles addressing the many ways in which extracellular matrix (ECM), or its components parts, can be used in regenerative medicine applications. ECM is a dynamic structure, composed of a three-dimensional architecture of fibrous proteins, proteoglycans, and glycosaminoglycans, synthesized by the resident cells. Consequently, ECM can be considered as nature’s ideal biologic scaffold material. The articles in this Special Issue cover a range of topics from the use of ECM components to manufacture scaffold materials, understanding how changes in ECM composition can lead to the development of disease, and how decellularization techniques can be used to develop tissue-derived ECM scaffolds for whole organ regeneration and wound repair. This editorial briefly summarizes the most interesting aspects of these articles.

Construction of novel antimicrobial peptide-modified extracellular matrix biologic scaffold material

In the field of implantable medical devices, the antibacterial extracellular matrix (ECM) biologic scaffold, which is constructed by modifying biomaterials with antibacterial peptides, has excellent potential. An antibacterial peptide–modified ECM scaffold was formed with chitosan (CS), antimicrobial peptide (AMP), and ECM scaffold. Chitosan has a firm positive-charge surface and can combine with the ECM scaffold material to form a positive-charge layer on the surface. The surface potential was characterized using a surface potential map. Infrared spectroscopy and scanning electron microscopy (SEM) were used to observe the scaffold surface characteristics and cell morphology. Fluorescence staining and MTS assay kit were used to assess cytotoxicity and biocompatibility. To evaluate the antibacterial and repairing effects on the infected wounds in vivo, a subcutaneous antibacterial test of rabbit back was conducted. The antibacterial peptide–modified ECM scaffold was successfully formed and presented an excellent three-dimensional micro-surface porous structure. The antibacterial peptide–modified ECM scaffold could be effectively-prepared by surface modification and activation. Fluorescence staining tests showed good cell adhesion, proliferation ability, and cell affinity. The in vivo experiment indicated that the antibacterial ECM scaffold had antibacterial and healing-promotion abilities.

Application of 3D biological nano scaffold materials in the health treatment of foot and ankle sports

Bone tissue is an important part of the human body and plays an indispensable physiological function. Damage to bone tissue will have a serious impact on the health of patients. Three types of MGPC scaffolds were prepared using 3D printing technology. The macroscopic, microstructure, and histology of the three scaffolds were observed under an electron microscope. The cells grew normally and spread well. Rat L-929 fibroblasts were cultured in three scaffold extracts, and the cells were cultured with DMEM as a control. Cell proliferation was detected by cell counting. Scanning electron microscopy of the cell-scaffold complex revealed that a large number of chondrocytes adhered and grew on the surface of the MGPC scaffold. With the increase of culture time, the number of cells in each group showed an increasing trend. MGPC has no cytotoxicity, excellent physical and chemical properties, and is expected to become a biological scaffold material.

Application and research of nano-biomaterials in ankle sports injury rehabilitation

The ankle joint is an important weight-bearing joint of the lower limbs. It converts the vertical gravity of the human body into an arched structure. When the ankle joint is exposed to external reaction forces and cannot be effectively cushioned, injuries can easily occur. If improper and untimely treatment can cause joint instability, easy to repeatedly sprain in the future, secondary joint adhesions or traumatic arthritis can cause dysfunction. Therefore, strengthening the treatment of ankle joint injury repair is of great significance to improve prognosis and improve clinical effect. Clinically, the treatment of ankle joint injury is mainly based on protection, rest, cold compress, and drug intervention. It is difficult to achieve the expected therapeutic effect. From a large amount of research data, with the development of tissue engineering and bioengineering, currently the use of artificial biological materials to intervene in the healing and rehabilitation of bone injuries has become increasingly mature, but it is relatively rare in rehabilitation measures for ankle sports injuries. Therefore, in this study, 3D printing technology was used to mix PHBV, calcium silicate, and bioactive glass to successfully prepare a bioglass scaffold BG-Si-PHBV. The micromorphology, porosity, water absorption, weight loss analysis and biomechanical characteristics of the biomaterial scaffold were studied. At the same time, this study established an ankle joint sports injury model with Beagle dogs, implanted BG-Si-PHBV biological bone tissue scaffold material into the ankle joint defect area of the affected limb of Beagle dogs, and detected BG-Si-PHBV tissue engineering materials to repair the ankle joint Feasibility of sports injuries. The BG-Si-PHBV biological bone tissue scaffold material prepared in this research has good porosity, hydrophilicity and biomechanical properties, which can meet the conditions of artificial biological materials after ankle injury. Animal experiments show that BG-Si-PHBV biological bone tissue scaffold is ideal for the rehabilitation of ankle joint sports injuries. This helps to improve the biomechanical properties and has broad application prospects.

Characterization of CS/PVA/GO electrospun nanofiber membrane with astaxanthin

AbstractTissue engineering has been widely used in regenerative medicine and tissue engineering scaffolds have become a new research direction for periodontal regenerative repair. We aim to develop a biological scaffold material that can support host immunity and promote periodontal regeneration. In this paper, chitosan (CS)/polyvinyl alcohol (PVA)/graphene oxide (GO)/astaxanthin (ASTA) nanofibers membranes were prepared by electrospinning. The nanofibers were characterized by scanning electron microscopy, infrared spectroscopy, mechanical testing, antibacterial testing and cytotoxicity testing. The CS/PVA/GO/ASTA nanofiber membrane had favorable micro‐morphology, good mechanical properties and no cytotoxicity. This preliminary study demonstrates that the CS/PVA/GO/ASTA nanofiber membrane can be used for in vivo and in vitro experiments related to periodontal regeneration. The related mechanism of periodontal regeneration will be evaluated in future studies.

Bioactive Tetracalcium Phosphate Scaffolds Fabricated by Selective Laser Sintering for Bone Regeneration Applications.

Tetracalcium phosphate (TTCP), a potential biological scaffold material, has attracted increasing interest for bone regeneration applications due to its good biodegradability and biocompatibility. In this research, three-dimensional porous TTCP scaffolds were manufactured via selective laser sintering (SLS), and an in-depth and meticulous study on the influence of laser power on the microstructure and mechanical properties of TTCP scaffolds was performed. The results showed that the TTCP particles fused together and formed a solid object due to the decrease in the number of micro-pores in the scaffold as the laser power increased from 6 W to 9 W. The maximum compressive strength that the scaffold could withstand and the strength of the fracture toughness were 11.87 ± 0.64 MPa and 1.12 ± 0.1 MPa·m1/2, respectively. When the laser power increased from 9 W to 10 W, the TTCP grains grew abnormally, resulting in diminished mechanical properties. The bioactivity tests showed that the surfaces of the scaffolds were entirely covered by bone-like apatite layers after soaking in simulated body fluid (SBF) for three days, indicating that the scaffolds exhibit excellent bioactivity. Moreover, cell experiments showed that the TTCP scaffolds had good biocompatibility. This study indicated that SLS-fabricated TTCP scaffolds may be a promising candidate for bone regeneration applications.

Extracellular Matrix-Based Biomaterials and Their Influence Upon Cell Behavior.

Biologic scaffold materials composed of allogeneic or xenogeneic extracellular matrix (ECM) are commonly used for the repair and remodeling of injured tissue. The clinical outcomes associated with implantation of ECM-based materials range from unacceptable to excellent. The variable clinical results are largely due to differences in the preparation of the material, including characteristics of the source tissue, the method and efficacy of decellularization, and post-decellularization processing steps. The mechanisms by which ECM scaffolds promote constructive tissue remodeling include mechanical support, degradation and release of bioactive molecules, recruitment and differentiation of endogenous stem/progenitor cells, and modulation of the immune response toward an anti-inflammatory phenotype. The methods of ECM preparation and the impact of these methods on the quality of the final product are described herein. Examples of favorable cellular responses of immune and stem cells associated with constructive tissue remodeling of ECM bioscaffolds are described.

Biological Influence of Nonswelling Microgels on Cartilage Induction of Mouse Adipose-Derived Stem Cells.

In cartilage tissue engineering, the target cells' functional performance depends on the biomaterials. However, it is difficult to develop an appropriate scaffold to differentiate mouse adipose-derived stem cells (mADSCs) into chondrocyte despite an increasing number of studies on biological scaffold materials. The purpose of this study was to create a novel scaffold for mADSC culture and chondrogenic differentiation with a new series of microgels based on polyethyleneimine (PEI), polyethylene glycol (PEG), and poly (L-lactic acid) (PLLA) and able to resist swelling with changes in temperature, pH, and polymer concentration. The biocompatibility and ability of the nonswelling microgels were then examined and served as scaffolds for cell culture and for cartilage differentiation. The results show that the new microgels are a novel biomaterial that both retains its nonswelling properties under various conditions and facilitates important scaffold functions such as cell adhesion, proliferation, and cartilage induction.

Comparison of extraction methods for isolating kafirin protein from food grade sorghum flour

Isolated sorghum (Sorghum bicolor) storage proteins (kafirins) have been successfully used in the production of several bio-materials including adhesives, films, micro-particles, fibers, and biological scaffold material. Comparatively little research has been conducted on the use of isolated kafirins in food products or to produce bioactive peptides via hydrolysis for nutritional uses. To support such research, the aim of this study was to compare existing methods for bulk isolation of sorghum kafirins with the goal of identifying a solvent with the least toxicity that maintained a high extraction rate from food grade sorghum flour. A secondary goal was to characterize the kafirin isolates produced from various extraction methods to provide some information on their potential use in food products to guide future research in this area. Five different extraction methods were compared including 1) aqueous ethanol containing NaOH and sodium metabisulfite, 2) glacial acetic acid, 3) aqueous ethanol with sodium metabisulfite, 4) aqueous ethanol at acidic pH, and 5) alkaline pH alone. The protein contents of the kafirin isolates obtained by the five methods ranged from 49.76% to 56.83%. Kafirin isolates were characterized using reversed phase (RP)-high performance liquid chromatography (HPLC), which revealed substantial variability in the various kafirin patterns among the extraction methods tested. However, characterization of the kafirin isolates by size exclusion chromatography (SEC) did not show a high degree of variability among the methods tested. Likewise, analysis of the samples using sodium dodecyl sulphate - polyacrylamide gel electrophoresis (SDS-PAGE) showed essentially the same band profiles but with different band intensities among kafirin extraction methods. Surface hydrophobicity of the kafirin isolates varied considerably with isolates extracted with glacial acetic acid and aqueous ethanol plus sodium metabisulfite the most hydrophobic as indicated by hydrophobic dye binding.