Sericin is a waste material from the silk production process, researchers its found to have good biological activity and is widely used in tissue engineering. The aim of this paper is to summarize the biological applications of sericin in the field of bone tissue engineering and their research progress. Randomized controlled trials, prospective or retrospective clinical studies, case series and reports, and systematic evaluations. MEDLINE, PubMed, and Google Scholar were searched using keywords. Sericin, has the ability to promote cell proliferation and angiogenesis. It also has excellent bone regenerative properties such as promoting osteoblast differentiation. Sericin itself has excellent physicochemical properties and can be processed into materials with different properties for bone regeneration engineering. Bone defects due to various skeletal diseases or surgical needs, etc are a major challenge for clinical treatment. Modern tissue engineering using synthetic osteogenic active materials offers another therapeutic option for bone defects, and sericin is expected to play a greater role as a promising biological material.

Background and Purpose:The skin is an important barrier to protect the body from external damage, there are tens of millions of patients with various skin defects. Due to the complex process of wound repair, it is easy to cause poor healing and other problems. Wound healing procedures have a systematic multi-stage: hemostasis, inflammation, proliferation and remodeling. Here, we prepared a new bio- responsive transdermal oil body microgel emulsion (OBEME) for drug delivery carrier. Experimental Approach: OBEME was stored at room temperature for 90 days, and its stability was evaluated by low speed centrifugation and repeated freeze-thaw treatment. The transdermal penetration of OBEME was proved by transdermal administration, and the effect of OBEME on wound healing was investigated in the model of full-thickness skin defect. Key Results: OBEME was stably stored at room temperature for 90 days and is not affected by low-speed centrifugation and repeated freeze-thaw. It was proved to have a good sustained release effect through percutaneous administration. The OBEME significantly promoted wound healing, regulated inflammatory response, and accelerated angiogenesis, re-epithelialization and remodeling. Conclusion and Implications: Taken together, the OBEME is a good new carrier for percutaneous drug delivery that can promote wound healing and it has a good sustained-release effect and can induce the correct repair of skin, which lays a foundation for the development of new topical drugs.

3D printed bone scaffolds have the potential to replace autografts and allografts because of advantages such as unlimited supply and the ability to tailor the scaffolds' biochemical, biological and biophysical properties. Significant progress has been made over the past decade in additive manufacturing techniques to 3D print bone grafts, but challenges remain in the lack of manufacturing techniques that can recapitulate both mechanical and biological functions of native bones. The purpose of this review is to outline the recent progress and challenges of engineering an ideal synthetic bone scaffold and to provide suggestions for overcoming these challenges through bioinspiration, high-resolution 3D printing, and advanced modeling techniques. The article provides a short overview of the progress in developing the 3D printed scaffolds for the repair and regeneration of critical size bone defects. STATEMENT OF SIGNIFICANCE: Treatment of critical size bone defects is still a tremendous clinical challenge. To address this challenge, diverse sets of advanced manufacturing approaches and materials have been developed for bone tissue scaffolds. 3D printing has sparked much interest because it provides a close control over the scaffold's internal architecture and in turn its mechanical and biological properties. This article provides a critical overview of the relationships between material compositions, printing techniques, and properties of the scaffolds and discusses the current technical challenges facing their successful translation to the clinic. Bioinspiration, high-resolution printing, and advanced modeling techniques are discussed as future directions to address the current challenges.

Negative pressure wound therapy (NPWT) results in improved wound repair and the combined use of NPWT with elastomeric materials may further stimulate and accelerate tissue repair. No firmly established treatment modalities using both NPWT and biomaterials exist for orthopedic application. The goal of this study was to investigate the response of osteoblasts and bone marrow-derived mesenchymal stem cells to negative pressure and to determine whether a newly developed elastic osteomimetic bone repair material (BRM), a blend of type I collagen, chondroitin 6-sulfate, and poly (octanediol citrate) could enhance the osteoblastic phenotype. The results indicate that proliferation and alkaline phosphatase activity of hFOB1.19 osteoblasts were significantly increased with exposure to 12 hr of negative pressure (-125 mmHg). Follow-on studies with rat and human mesenchymal stem cells confirmed that negative pressure enhanced osteoblastic maturation. In addition, a significant interaction of negative pressure and electrospun BRM resulted in increased mRNA expression of alkaline phosphatase, osteopontin, collagen1α2, and HIF1α, whereas little or no effect on these genes was observed on electrospun collagen or tissue culture plastic. Together, these results suggest that the use of this novel biomaterial, BRM, with NPWT may ultimately translate into a safe and cost-effective clinical application to accelerate bone repair.

Mesenchymal stem cell (MSC) differentiation is regulated by surface modification including texturing, which is applied to materials to enhance tissue integration. Here, we used Pt 57.5 Cu 14.7 Ni 5.3 P 22.5 bulk metallic glass (Pt-BMG) with nanopatterned surfaces achieved by thermoplastic forming to influence differentiation of human MSCs. Pt-BMGs are a unique class of amorphous metals with high strength, elasticity, corrosion resistance, and an unusual plastic-like processability. It was found that flat and nanopattened Pt-BMGs induced osteogenic and adipogenic differentiation, respectively. In addition, osteogenic differentiation on flat BMG exceeded that observed on medical grade titanium and was associated with increased formation of focal adhesions and YAP nuclear localization. In contrast, cells on nanopatterned BMGs exhibited rounded morphology, formed less focal adhesions and had mostly cytoplasmic YAP. These changes were preserved on nanopatterns made of nanorods with increased stiffness due to shorter aspect ratios, suggesting that MSC differentiation was primarily influenced by topography. These observations indicate that both elemental composition and nanotopography can modulate biochemical cues and influence MSCs. Moreover, the processability and highly tunable nature of Pt-BMGs enables the creation of a wide range of surface topographies that can be reproducibly and systematically studied, leading to the development of implants capable of engineering MSC functions.

Negative pressure wound therapy has been used to accelerate clinical wound healing, however few have suggested applications for bone healing and potential pathways. In order to modulate the natural bone repair and make in vivo repair feasible, degradable materials for negative pressure wound therapy were designed. We fabricated and tested an electrospun composite of Type I collagen, chondroitin 6‐sulfate and Poly (1,8‐octanediol‐co‐citrate), termed BRM, that mimicked extracellular environment with collagen and elastin imbedded in a matrix of proteoglycans and glycoproteins. A closed chamber system was designed to generate and monitor negative pressure environments and conditions for osteoblast growth. When cultured on BRM and plastic dish with and without negative pressure, the cell proliferation was significantly greater (P<0.05) on BRM compared to electrospun collagen. With a negative pressure of ‐125mmHg, alkaline phosphatase activity was increased by Day 7 and osteoblast proliferation was increased by 1.3 folds on Day 17. The closed chamber system will be used to exam molecular pathways by the interactions of BRM and negative pressure on bone marrow derived stem cells. This study permits the evaluation of material design and feasibility of negative pressure to be explored for the accelerated bone healing.

Degradable biomaterials with tunable mechanical, compositional and structural properties have been developed for fusion of bone; however few have demonstrated enhanced repair rates or formation of quality bone compared to autologous bone grafts. The purpose of this study was to fabricate and test a new nanocomposite to mimic extracellular matrix and accelerate spine fusion. An electrospun composite of Type I collagen, chondroitin 6‐sulfate and Poly (1,8‐octanediol‐co‐citrate), termed BRM, was fabricated and tested in a sheep model of lumbar vertebrae fusion. By SEM, BRM had mean fiber diameters of 528±46nm (mean±SEM). Osteoblasts were cultured on BRM and had significantly greater (P<0.05) proliferation compared to electrospun collagen. BRM or autologous bone was placed into PEEK cages and surgically implanted to evaluate posterior lumbar interbody fusion. Fusion sites were monitored by CT and evaluated over a 6 weeks period followed by histologic evaluation. At 6 weeks, mean CT units were 259±45 for BRM and 231±45 (mean±SEM) for autologous bone (noninjured site was 614). Histologic evaluation demonstrated integration and replacement of BRM and significant osteoblastic activity at fusion sites. BRM promoted osteoblastic activity and was bioresorbed without extensive inflammation. BRM resulted in accelerated spine fusion and demonstrated comparable effectiveness as autologous bone graft. The viscoelasticity of BRM and the presence of growth factor binding sites on collagen and chondroitin sulfate may act in concert to promote bone formation.

Development of resorbable elastic composites as an alternative means to apply contractive forces for manipulating craniofacial bones is described herein. Composites made from the biodegradable elastomer, poly (1,8-octanediol co-citric acid) (POC), and hydroxyapatite (nHA) with a 200 nm diameter (0-20% loadings) were created to develop a material capable of applying continuous contractive forces. The composites were evaluated for variation in their mechanical properties, rate of degradation, and interaction of the hydroxyapatite nanoparticles with the polymer chains. First, an ex vivo porcine model of cleft palate was used to determine the rate of cleft closure with applied force. The closure rate was found to be 0.505 mm N(-1) . From this approximation, the ideal maximum load was calculated to be 19.82 N, and the elastic modulus calculated to be 1.98 MPa. The addition of nHA strengthens POC, but also reduces the degradation time by 45%, for 3% nHA loading, compared to POC without nHA. X-ray diffraction data indicates that the addition of nHA to amorphous POC results in the formation of a semicrystalline phase of the POC adjacent to the nHA crystals. Based on the data, we conclude that amongst the 0-20% nHA loadings, a 3% loading of nHA in POC may be an ideal material (1.21 MPa elastic modulus and 13.17 N maximum load) to induce contraction forces capable of facilitating osteogenesis and craniofacial bone repair.

Conventional collagen-based heart valves eventually fail because of insufficient replacement of graft material by host tissue. In this study, type I collagen was blended with silk fibroin and the synthetic elastic polymer poly (glycerol-sebacate) (PGS) in varying proportions to create multifunctional electrospun nanofibrous materials tailored for use as endovascular scaffolds such as heart valve replacement. Depending on the blended material the elastic moduli ranged from 2.3 to 5.0 Mpa; tensile stresses ranged from 0.8 to 1.5 Mpa; and strains ranged from 30% to 70%. Electrospun materials with a weight ratio of 4.5:4.5:1 (collagen, fibroin, and PGS) (termed PFC mats) were the most similar to native heart valves. In vitro degradation of PFC mats was 0.01% per week. Endothelial cells adhered to, proliferated, and formed cell-cell junctions on PFC mats. Compared with collagen hydrogels and electrospun collagen mats respectively 220-290% less platelet adhesion was observed for PFC mats. The study demonstrates that PFC material has superior mechanical properties, low degradation, and reduced thrombogenic potential and suggests that further investigation of this biomaterial for cardiovascular applications is warranted. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1150-1158, 2015.

Ischemia-reperfusion injury induces large differences in hydration potential between ischemic and nonischemic areas of the myocardium. They influence the rate and volume of fluid transfer in myocardial explants; temperature-dependent hydration-potential differences of approximately 100 mmHg in at-risk areas, as opposed to contiguous areas that are not at risk, suggest prompt interstitial fluid-transfer control mechanisms (Circ. Res . 2012;11:A235) . Aim: We adapted osmotic-stress techniques to determine whether myocardial fibroblasts, which are known to respond to mechanical and flow signals, also respond to hydration-potential changes. Methods: Fibroblasts were isolated from midwall regions of the left ventricles of healthy pigs using standard procedures. They were incorporated into 3-dimensional collagen gels of 500 mm 3 volume at 150 cells/mm 3 and equilibrated overnight in cultures using the nontoxic, inert polymer polyethylene glycol 8000 (molecular radius ~26.5 Å; concentration range 0-10% w/w) to adjust colloidosmotic pressure from approximately 5 to 205 mmHg . After the gels were detached from the dish, fluid flux was derived from any time-dependent changes in their dimensions. Results: The volume of gels without fibroblasts did not change significantly at any coloidosmotic pressure. In those with fibroblasts, the volume decreased, more slowly in those subjected to higher-than-plasma pressure levels. Progression curves conformed well to a two-exponential term model (R 2 >0.9) suggesting that two parallel processes contribute to matrix efflux, one relatively fast, with decay constant 0.274 ± 0.014 (n = 3) , and another ~50-fold slower. Initial rates were calculated from the fitted curves, and linear regression analysis used to examine their dependence on colloidosmotic pressure. Initial efflux rates decreased with pressure, mean slope, - 0.29 ± 0.08 µl/h/mmHg (R 2 = 0.7; P-value = 0.006). Conclusion: In vitro , fibroblasts in collagen matrices regulate fluid efflux in response to colloidosmotic stresses within the range of hydration-potential differences measured in myocardial explants after ischemia-reperfusion injury.

Mechanical or collagen based porcine valves currently used to replace diseased or nonfunctional valves are subject to thrombosis, material failure, or inadequate in situ remodeling. In this study a new electrospun nanofiber composite was fabricated from mechanically robust silk fibroin, (F), Type I collagen (C), and the synthetic elastic polymer, poly (glycerol‐sebacate) (P). Materials fabricated with different weight ratios of F:C:P had an elastic modulus between 2.8–4.1 Mpa; tensile stresses from 1.1–1.5 Mpa and strains between 41–44% which were similar to values reported for native heart valve. In vitro degradation demonstrated <0.3% mass loss per week with no change in nanofiber diameter. In culture electrospun nanofibers mats of FCP compared to structurally similar C nanofibers had greater human umbilical vein endothelial cell growth and by confocal microscopy demonstrated tight intercellular junctions. Using human platelet rich plasma reduced platelet numbers were observed for FCP (3440 ± 302) (mean ± SEM, platelets/cm2)mats compared to C (5268 ± 848) and collagen gels (27,549 ± 698). By SEM, platelets appeared significantly less activated on FCP. Materials preseeded with cells had platelet adhesion of 555 ± 137, 1588 ± 41, and 12311 ± 208 respectfully for FCP, C, and collagen gels. The findings suggest FCP may be a superior material for heart valve replacement.