Micro-Porous PLLA Scaffolds for Orthopedic Surgical Fixation Devices

Author(s):  
Qingwei Zhang ◽  
Wei Zhang ◽  
Donggang Yao ◽  
David M. Wootton ◽  
Peter I. Lelkes ◽  
...  

Anterior cruciate ligament (ACL) reconstructive surgery is a major health concern world-wide because of a large aging population and increased occurrence of sport-related injuries. Tissue engineering is a rapidly growing interdisciplinary field that offers a promising new approach for ACL repair. The aim of this project is to explore novel “smart” surgical fixation devices that not only secure a graft in place without strength failure, but also incorporate and release bioactive materials, intended to promote bone tissue growth. In order to facilitate bioactive reagent release, biopolymeric scaffolds with continuous micro-porous structure were developed. The morphology of the porous structures in the poly-L-lactic acid (PLLA) matrix reflects the differential influence of the concentration of sacrificial material (PS-polystyrene), phase separation levels of the immiscible polymers (PLLA and PS), and melt-blending conditions (Fig. 1) [1]. During removal of the sacrificial material, the chemical solvent might introduce some chemical reactant into the scaffolds. In order to assess the feasibility of using the micro-porous structures for medical applications, 7F2 osteoblasts were cultured on these scaffolds for 7 days. The attachment and proliferation of 7F2 cells on all scaffolds were assessed by fluorescent nuclear staining with Hoechst 33258 and phalloidin. The morphology of 7F2 osteoblasts on solid PLLA and PLLA/HA with 40% porous structure scaffolds till the 7 days pos-seeding was observed under confocal microscopy (Fig. 2A and B). The results showed that removal of the sacrificial material does not influence cell growth and the composites are biocompatible. Besides in vitro cytotoxicity test, in vivo test of all the micro-porous structural scaffolds was performed through rat subcutaneous surgery. Histological analysis (H&E staining) of the porous PLLA/HA with 40% pores retrieved from rat subcutaneous tissue 4 weeks postimplantation show that cells start to grow inside the porous scaffold (Fig. 3A). The morphology of surrounding extracellular matrix (ECM) growing on the scaffolds was observed under SEM. Figure 3B shows soft tissue attached onto PLLA/HA porous scaffold after 1 month post implantation time point, which indicates the good biocompatibility of the scaffolds. Based on these data we predict that these scaffolds will be suitable for inducing and sustaining bone tissue regeneration, and will be feasible for ACL repair.

Author(s):  
Qingwei Zhang ◽  
Wei Zhang ◽  
Donggang Yao ◽  
Peter I. Lelkes ◽  
Jack G. Zhou

Anterior cruciate ligament (ACL) reconstructive surgery is a major health concern world-wide because of a large aging population and increased occurrence of sport-related damage. Tissue engineering is a rapidly growing interdisciplinary field that offers a promising new approach for ACL repair. In order to overcome the shortages of current existing surgical fixation devices, we are combining gradient cellular structure (GCS) injection molding technique and biomedical engineering to develop novel surgical fixation devices (screw, anchor, plate, pin, staple, etc.) that not only incorporate bioactive materials such as growth factors, healing drugs and cells, but have natural bone GCS structure, intended to mimic the natural bone and promote bone tissue growth and eventually eliminate the defects associated with existing surgical fixation devices. In this work, a series of novel poly-L-lactic acid (PLLA) scaffolds with micro-porous structure were prepared by injection molding an immiscible polymer blend, with spatially controlled thermal conditioning to adjust the phase size from core to surface. The produced scaffolds were observed under SEM, which shows a co-continuous structure was created successfully through our method. The biocompatibility and the feasibility of produced micro-porous structural PLLA and PLLA/HA scaffolds as a matrix supporting cell growth tested by culturing murine osteoblasts cell line (7F2) for up to 9 days were assessed by Alamar Blue™ assay, which showed that the manufacturing process had no negative effects on cell proliferation. The cell attachment, spreading, migration and proliferation to confluence were assessed by fluorescent nuclear staining with Hoechst 33258. In order to evaluate the functional and cell biological applicability of the micro-porous structural PLLA scaffolds, a subcutaneous biodegradation test was performed through rat model for 1 week and 1 month time period, respectively. Our results showed that the micro-porous structural PLLA scaffolds are non-toxic, and they showed a mild foreign body reaction and complete fibrous encapsulation after implantation. Well created interconnected porous structure and biocompatibility suggest great potential of the micro-porous PLLA scaffolds in application for ACL reconstruction.


Author(s):  
Qingwei Zhang ◽  
Wei Zhang ◽  
Jephte Augustin ◽  
Donggang Yao ◽  
David M. Wootton ◽  
...  

Tissue engineering is a rapidly growing interdisciplinary field which offers a promising new technology to create artificial constructs for regeneration of tissues. One important aspect of bone tissue engineering is to build scaffolds with interconnected 3-D porous structure in order to mimic natural bone architecture. In this work, co-continuous micro-porous scaffolds made of Poly-L-lactic acid (PLLA) with 50% porosity and PLLA/hydroxyapatite (HA) with 40% porosity were prepared by injection molding of an immiscible polymer blend with polystyrene as sacrificial material. The sacrificial material was then removed by solvent leaching with cyclohexane. The porous PLLA/HA matrix supported murine osteoblast (7F2) cell growth for up to 9 days, suggesting that that the introduction and replacement of sacrificial material had no negative effects on cell proliferation. In vitro studies also indicate an increase in mineralization by osteoblasts cultured on the porous structure, as compared to cells cultured on solid scaffold. One month subcutaneous degradation tests showed a mild foreign body reaction and complete fibrous encapsulation. Following surgical implantation of the scaffolds into circular defects in canine tibia, we observed after 12 weeks new bone tissue grew into the porous structures. Taken together our data suggest that interconnected porous structures with good cytocompatibility and increased mineralization in vitro paired with enhanced osteoinductive properties in vivo suggest a great potential of the porous PLLA/HA for inducing and sustaining bone tissue repair.


Author(s):  
Qingwei Zhang ◽  
Vadym Mochalin ◽  
Ioannis Neitzel ◽  
Yury Gogotsi ◽  
Peter I. Lelkes ◽  
...  

Biopolymers have a great potential in biomedical engineering, having been used as scaffolds for hard and soft tissues, such as bone and blood vessels for many years. More recently biopolymers have also found applications in surgical fixation devices. Compared with conventional metal fixation devices, bone grafts and organ substitutes, biopolymer products have advantages of no long-term implant palpability or temperature sensitivity, predictable degradation to provide progressive bone loading and no stress shielding, all of which leads to a better bone healing, reduced patient trauma and cost, elimination of second surgery for implant removal, and fewer complications from infections. However lack of initial fixation strength and bioactivity are two major concerns which limited more widespread applications of biopolymers in orthopedic surgery. Nanodiamond is attractive for its use in reinforcement of composite materials due to their outstanding mechanical, chemical and biological properties. Nanotechnology shows us many innovations and it is generally accepted view that many could be further developed and applied in tissue engineering. In this work, we conduct poly(L-lactic acid) (PLLA) and octadecylamine functionalized nanodiamond (ND-ODA) composite research to optimize the polymer/ND interface, thus to reinforce the mechanical strength. Composites comprising PLLA matrix with embedded ND-ODA were prepared by mixing PLLA/chloroform solution with chloroform suspension of nanodiamonds at concentrations of 0–10 by weight percent. The dispersion of ND-ODA was observed by transmission electron microscopy (TEM). TEM micrographs show that ND-ODA can disperse uniformly in PLLA till 10% wt. Nanoindentation result shows the mechanical strength of ND-ODA/PLLA composites improving following increasing the concentration of ND-ODA in composites. The noncytotoxicity of ND-ODA was demonstrated on 7F2 Osteoblasts. To test the usefulness of ND-ODA/PLLA composites as scaffolds for supporting cell growth, 7F2 Osteoblasts were cultured on scaffolds for 6 days. The attachment and proliferation of 7F2 on all scaffolds were assessed by fluorescent nuclear staining with Hoechst 33258 and Alamar BlueTM assay. The results showed that the adding ND-ODA does small influence cell growth, which indicates the composites have good biocompatibility. The morphology of 7F2 cells growing on all ND-ODA/PLLA composite scaffolds was determined by SEM, which confirms the Osteoblasts spread on the scaffolds. All these results combined suggest that ND-ODA/PLLA might provide a novel composite suitable for surgical fixation devices.


Micromachines ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 664
Author(s):  
Haiyuan Zhao ◽  
Yafeng Han ◽  
Chen Pan ◽  
Ding Yang ◽  
Haotian Wang ◽  
...  

In order to obtain scaffold that can meet the therapeutic effect, researchers have carried out research on irregular porous structures. However, there are deficiencies in the design method of accurately controlling the apparent elastic modulus of the structure at present. Natural bone has a gradient porous structure. However, there are few studies on the mechanical property advantages of gradient bionic bone scaffold. In this paper, an improved method based on Voronoi-tessellation is proposed. The method can get controllable gradient scaffolds to fit the modulus of natural bone, and accurately control the apparent elastic modulus of porous structure, which is conducive to improving the stress shielding. To verify the designed structure can be fabricated by additive manufacturing, several designed models are obtained by SLM and EBM. Through finite element analysis (FEA), it is verified that the irregular porous structure based on Voronoi-tessellation is more stable than the traditional regular porous structure of the same structure volume, the same pore number and the same material. Furthermore, it is verified that the gradient irregular structure has a better stability than the non-gradient structure. An experiment is conducted successfully to verify the stability performance got by FEA. In addition, a dynamic impact FEA is also performed to simulate impact resistance. The result shows that the impact resistance of the regular porous structure, the irregular porous structure and the gradient irregular porous structure becomes better in turn. The mechanical property verification provides a theoretical basis for the structural design of gradient irregular porous bone tissue engineering scaffolds.


2020 ◽  
Vol 40 (7) ◽  
pp. 591-599
Author(s):  
Yaling Tian ◽  
Kai Liang ◽  
Yali Ji

AbstractThe citrate-based thermoset elastomer is a promising candidate for bone scaffold material, but the harsh curing condition made it difficult to fabricate porous structure. Recently, poly (1, 8-octanediol-co-Pluronic F127 citrate) (POFC) porous scaffold was creatively fabricated by chitin nanofibrils (ChiNFs) supported emulsion-freeze-casting. Thanks to the supporting role of ChiNFs, the lamellar pore structure formed by directional freeze-drying was maintained during the subsequent thermocuring. Herein, bioactive glass (BG) was introduced into the POFC porous scaffolds to improve bioactivity. It was found the complete replacement of ChiNF particles with BG particles could not form a stable porous structure; however, existing at least 15 wt% ChiNF could ensure the formation of lamellar pore, and the interlamellar distance increased with BG ratios. Thus, the BG granules did not contribute to the formation of pore structure like ChiNFs, however, they surely endowed the scaffolds with enhanced mechanical properties, improved osteogenesis bioactivity, better cytocompatibility as well as quick degradation rate. Reasonably adjusting BG ratios could balance the requirements of porous structure and bioactivity.


Nano LIFE ◽  
2012 ◽  
Vol 02 (01) ◽  
pp. 1250005 ◽  
Author(s):  
BIN DUAN ◽  
MIN WANG ◽  
WILLIAM W. LU

Selective laser sintering (SLS), a rapid prototyping technology, was investigated for producing bone tissue engineering scaffolds. Completely biodegradable osteoconductive calcium phosphate (Ca-P)/poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) scaffolds were successfully fabricated via SLS using Ca-P/PHBV nanocomposite microspheres. In the SLS manufacturing route, the architecture of tissue engineering scaffolds (pore shape, size, interconnectivity, etc.) can be designed and the sintering process can be optimized for obtaining scaffolds with desirable porous structures and mechanical properties. SLS was also shown to be very effective in producing highly complex porous structures using nanocomposite microspheres. To render SLS-formed Ca-P/PHBV scaffolds osteoinductive, recombinant human bone morphogenetic protein-2 (rhBMP-2) could be loaded onto the scaffolds. For achieving a controlled release of rhBMP-2 from scaffolds, surface modification of Ca-P/PHBV scaffolds by gelatin entrapment and heparin immobilization was needed. The immobilized heparin provided binding affinity for rhBMP-2. Surface modified Ca-P/PHBV nanocomposite scaffolds loaded with rhBMP-2 enhanced the proliferation of human umbilical cord derived mesenchymal stem cells (hUCMSCs) and also their alkaline phosphatase activity. In in vivo experiments using a rabbit model, surface modified Ca-P/PHBV nanocomposite scaffolds loaded with rhBMP-2 promoted ectopic bone formation, exhibiting their osteoinductivity. The strategy of combining advanced scaffold fabrication, nanocomposite material, and controlled growth factor delivery is promising for bone tissue regeneration.


RSC Advances ◽  
2017 ◽  
Vol 7 (69) ◽  
pp. 43356-43365 ◽  
Author(s):  
Yuanyuan Li ◽  
Kaiwen Zheng ◽  
Sayyed Asim Ali Shah ◽  
Yizhou Huang ◽  
Yazhou Tian ◽  
...  

The synthesized JC samples possessed abundant self-doped heteroatoms and hierarchically porous structures (the co-existence of micro-, meso-, and macropores).


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