Scaffolds For Tissue Repair Research Articles

Impact of Annealing Chemistry on the Properties and Performance of Microporous Annealed Particle Hydrogels.

Microporous annealed particle (MAP) hydrogels are a promising class of in situ-forming scaffolds for tissue repair and regeneration. While an expansive toolkit of annealing chemistries has been described, the effects of different annealing chemistries on MAP hydrogel properties and performance have not been studied. In this study, we address this gap through a controlled head-to-head comparison of poly(ethylene glycol) (PEG)-based MAP hydrogels that were annealed using tetrazine-norbornene and thiol-norbornene click chemistry. Characterization of material properties revealed that tetrazine click annealing significantly increases MAP hydrogel shear storage modulus and results in slower in vitro degradation kinetics when microgels with a higher cross-link density are used. However, these effects are muted when the MAP hydrogels are fabricated from microgels with a lower cross-link density. In contrast, in vivo testing in murine critical-sized calvarial defects revealed that these differences in physicochemical properties do not translate to differences in bone volume or calvarial defect healing when growth-factor-loaded MAP hydrogel scaffolds are implanted into mouse calvarial defects. Nonetheless, the impact of tetrazine click annealing could be important in other applications and should be investigated further.

Comparative Analysis of Decellularization Methods on Bovine Pericardium Scaffolds for Cardiac Tissue Engineering

Background: Congenital heart disease (CHD) involves structural heart abnormalities present since fetal development. Corrective surgery is often the ideal treatment, utilizing implants or scaffolds for tissue repair. However, repeated surgeries may be required due to declining function of grafts, leading to increased healthcare costs. Bovine pericardium is a promising scaffold material for tissue engineering due to its composition of collagen, glycosaminoglycans (GAGs), and proteoglycans. This study aimed to compare the effectiveness of bovine pericardium scaffolds using different decellularization methods: sodium dodecyl sulfate (SDS) and hydrogen peroxide (H2O2). Methods: An experimental study was conducted with bovine pericardium scaffolds divided into control and treatment groups. The treatment groups used decellularization with SDS (0.5%, 1%) and H2O2 (3%). Scaffolds were evaluated for tensile strength, strain, Young's modulus, and histological properties, including nuclear density, collagen density, and GAG content. Data were analyzed using statistical methods to compare the effectiveness of each decellularization technique. Results: Histological analysis revealed that all decellularized samples showed no nuclear density, while control samples displayed light nuclear density. Collagen density was light in scaffolds treated with SDS 0.5% and H2O2, while SDS 1% resulted in no collagen presence. GAG density was absent in SDS-treated samples and minimal in H2O2-treated samples. Tensile strength was highest in H2O2-treated scaffolds (24.01 N) and lowest in SDS 0.5%. SDS 1% showed the greatest tensile strain, while H2O2-treated scaffolds had the highest stiffness. Conclusion: The decellularization methods effectively removed cellular components from the bovine pericardium scaffolds, with varying impacts on the extracellular matrix. SDS 1% provided the most elastic scaffold, while H2O2 preserved tensile strength and stiffness. These findings suggest that the choice of decellularization method can be optimized based on the desired mechanical properties of the scaffold for cardiac tissue engineering applications. Further research is needed to evaluate the long-term performance of these scaffolds in clinical settings.

Unlocking the Power of Amniotic Membrane in Endodontic Care: A Review Article

Amniotic membrane (AM) has garnered significant interest in endodontics for its regenerative properties. This membrane, sourced from the placenta, offers a unique combination of anti-inflammatory, anti-fibrotic, and wound healing properties. In endodontics, AM has shown promise in regenerating damaged periapical tissues, promoting revascularization, and enhancing the success of root canal treatments. It serves as a scaffold for tissue repair and modulates the inflammatory response, aiding in faster healing and reducing post-operative complications. This abstract highlights the potential of AM in revolutionizing endodontic procedures by providing a natural, biocompatible, and effective means for tissue regeneration and repair. Keywords ­ Amniotic membrane, Regenerative Endodontics, Scaffolds, Root End Surgery

Zirconium ion mediated collagen nanofibrous hydrogels with high mechanical strength

Low mechanical strength is still the key question for collagen hydrogel consisting of nanofibrils as hard tissue repair scaffolds with no loss of biological function. In this work, novel collagen nanofibrous hydrogels with high mechanical strength were fabricated based on the pre-protection of trisodium citrate masked Zr(SO4)2 solution for collagen self-assembling nanofibrils and then further coordination with Zr(SO4)2 solution. The mature collagen nanofibrils with d-period were observed in Zr(IV) mediated collagen hydrogels by AFM when the Zr(IV) concentration was ≥ 10 mmol/L, and the distribution of zirconium element was uniform. Due to the coordination of Zr(IV) with ─COOH, ─NH2 and ─OH within collagen and the tighter entanglement of collagen nanofibrils, the elastic modulus and compressive strength of Zr(IV) mediated collagen nanofibrous hydrogel were 208.3 and 1103.0 kPa, which were approximate 77 and 12 times larger than those of pure collagen hydrogel, respectively. Moreover, the environmental stability such as thermostability, swelling ability and biodegradability got outstanding improvements and could be regulated by Zr(IV) concentration. Most importantly, the resultant hydrogel showed excellent biocompatibility and even accelerated cell proliferation.

Application of metal-organic frameworks-based functional composite scaffolds in tissue engineering.

With the rapid development of materials science and tissue engineering, a variety of biomaterials have been used to construct tissue engineering scaffolds. Due to the performance limitations of single materials, functional composite biomaterials have attracted great attention as tools to improve the effectiveness of biological scaffolds for tissue repair. In recent years, metal-organic frameworks (MOFs) have shown great promise for application in tissue engineering because of their high specific surface area, high porosity, high biocompatibility, appropriate environmental sensitivities and other advantages. This review introduces methods for the construction of MOFs-based functional composite scaffolds and describes the specific functions and mechanisms of MOFs in repairing damaged tissue. The latest MOFs-based functional composites and their applications in different tissues are discussed. Finally, the challenges and future prospects of using MOFs-based composites in tissue engineering are summarized. The aim of this review is to show the great potential of MOFs-based functional composite materials in the field of tissue engineering and to stimulate further innovation in this promising area.

Small intestine submucosa as a growth factor attractor promotes peripheral nerve regeneration by enhancing syndecan-3/glial cell line-derived neurotrophic factor (GDNF) signalling: in vivo study * *Grant sponsor: The Ministry of Science and Technology (Taiwan); Grant number: 111-2320-B-005-009-MY3.

Peripheral nerve regeneration (PNR) following trauma requires the reconstruction of the extracellular matrix (ECM) and the proper stimulation of growth factors. Decellularised small intestine submucosa (SIS) has been extensively used as an ECM scaffold for tissue repair, but its potential to enhance the effects of exogenous growth factors on PNR is not well understood. In this study, we evaluated the effects of SIS implantation combined with glial cell-derived growth factor (GDNF) treatment on PNR in a rat neurorrhaphy model. We found that both SIS and regenerating nerve tissue expressed syndecan-3 (SDC3), one of major heparan sulphate proteoglycans in nerve tissue, and that SDC3 interacted with GDNF in the regenerating nerve tissue. Importantly, the SIS-GDNF combined treatment enhanced the recovery of neuromuscular function and β3-tubulin-positive axonal outgrowth, indicating an increase in the number of functioning motor axons connecting to the muscle after neurorrhaphy. Our findings suggest that the SIS membrane offers a new microenvironment for neural tissue and promotes neural regeneration based on SDC3-GDNF signalling, providing a potential therapeutic approach for PNR.

PH-Responsive Reversible Granular Hydrogels Based on Metal-Binding Mussel-Inspired Peptides.

Taking advantage of their thixotropic behavior, microporosity, and modular properties, granular hydrogels formed from jammed hydrogel microparticles have emerged as an exciting class of soft, injectable materials useful for numerous applications, ranging from the production of biomedical scaffolds for tissue repair to the therapeutic delivery of drugs and cells. Recently, the annealing of hydrogel microparticles in situ to yield a porous bulk scaffold has shown numerous benefits in regenerative medicine, including tissue-repair applications. Current annealing techniques, however, mainly rely either on covalent connections, which produce static scaffolds, or transient supramolecular interactions, which produce dynamic but mechanically weak hydrogels. To address these limitations, we developed microgels functionalized with peptides inspired by the histidine-rich cross-linking domains of marine mussel byssus proteins. Functionalized microgels can reversibly aggregate in situ via metal coordination cross-linking to form microporous, self-healing, and resilient scaffolds at physiological conditions by inclusion of minimal amounts of zinc ions at basic pH. Aggregated granular hydrogels can subsequently be dissociated in the presence of a metal chelator or under acidic conditions. Based on the demonstrated cytocompatibility of these annealed granular hydrogel scaffolds, we believe that these materials could be developed toward applications in regenerative medicine and tissue engineering.

A Review on Textile Scaffolds – For an Effective Healing and Regeneration

The underlying principle of tissue engineering is the development of biological alternates that involve an integrative field of both life sciences and engineering. The chapter features the basics of tissue engineering, the strategy for the selection of scaffolds and different types of materials used and their properties and highlights the employment of textile structures as scaffolds for tissue repair. The fabrication methodologies of various textile structures and their design are also outlined.

Decellularization compromises mechanical and structural properties of the native trachea

Tracheal replacement using tissue engineering technologies offers great potential to improve previously intractable clinical interventions, and interest in this area has increased in recent years. Many engineered airway constructs currently rely on decellularized native tracheas to serve as the scaffold for tissue repair. Yet, mechanical failure leading to airway narrowing and collapse remains a major cause of morbidity and mortality following clinical implantation of decellularized tracheal grafts. To understand better the factors contributing to mechanical failure in vivo, we characterized the histo-mechanical properties of tracheas following two different decellularization protocols, including one that has been used clinically. All decellularized tracheas deviated from native mechanical behavior, which may provide insights into observed in vivo graft failures. We further analyzed protein content by western blot and analyzed microstructure by histological staining and found that the specific method of decellularization resulted in significant differences in the depletion of proteoglycans and degradation of collagens I, II, III, and elastin. Taken together, this work demonstrates that the heterogeneous architecture and mechanical behavior of the trachea is severely compromised by decellularization. Such structural deterioration may contribute to graft failure clinically and limit the potential of decellularized native tracheas as viable long-term orthotopic airway replacements.

Electrospun polycaprolactone scaffolds loaded with a 1,4-naphthoquinone derivative for anticancer therapy

• Novel materials for tissue repair after surgical resection of tumors are needed. • Naphthoquinones have been reported to be effective for anticancer therapy. • Electrospun PCL-based scaffolds were loaded with a 1,4-naphthoquinone derivative. • Anticancer activity was retained, yet mechanical properties did not change for doped scaffolds. The development of bioresorbable scaffolds with anticancer properties for use in tissue repair after surgical resection of tumors is important. Naphthoquinones with high anticancer activity are promising compounds for creating anticancer scaffolds. Thus, electrospun polycaprolactone (PCL) scaffolds embedded with different concentrations of 2-chloro-3-((4-hydroxyphenyl)amino)-1,4-naphthoquinonone (NQCP4) were fabricated without changing the technological parameters of scaffold formation. Loading NQCP4 into the spinning solution at concentrations of 10 to 50 μg/mL did not cause changes in the structure, strength, or wettability of the scaffold. However, increasing NQCP4 concentrations in the spinning solution enhanced anticancer properties of the scaffolds in vitro . Thus, the use of NQCP4 makes it possible to obtain promising PCL scaffolds for tissue repair, which are in demand for surgical resection of malignant neoplasms, while still maintaining the technological advantages of “classical” electrospinning technology.

Proteomic Analysis of Decellularized Extracellular Matrix: Achieving a Competent Biomaterial for Osteogenesis.

Decellularized ECMs have been used as biological scaffolds for tissue repair due to their tissue-specific biochemical and mechanical composition, poorly simulated by other materials. It is used as patches and powders, and it could be further processed via enzymatic digestion under acidic conditions using pepsin. However, part of the bioactivity is lost during the digestion process due to protein denaturation. Here, stepwise digestion was developed to prepare a competent biomaterial for osteogenesis from three different ECM sources. In addition, three different proteases were compared to evaluate the most effective digestion protocol for specific cellular processes. GAGs and peptide quantification showed that the stepwise method yielded a higher concentration of bioactive residues. Circular dichroism analysis also showed that the stepwise approach preserved the secondary structures better. The protein profiles of the digested ECMs were analyzed, and it was found to be highly diverse and tissue-specific. The digestion of ECM from pericardium produced peptides originated from 94 different proteins, followed by 48 proteins in ECM from tendon and 35 proteins in ECM from bone. In addition, digested products from pericardium ECM yielded increased proliferation and differentiation of bone marrow mesenchymal stem cells to mature osteoblasts.

Topographic Orientation of Scaffolds for Tissue Regeneration: Recent Advances in Biomaterial Design and Applications.

Tissue engineering to develop alternatives for the maintenance, restoration, or enhancement of injured tissues and organs is gaining more and more attention. In tissue engineering, the scaffold used is one of the most critical elements. Its characteristics are expected to mimic the native extracellular matrix and its unique topographical structures. Recently, the topographies of scaffolds have received increasing attention, not least because different topographies, such as aligned and random, have different repair effects on various tissues. In this review, we have focused on various technologies (electrospinning, directional freeze-drying, magnetic freeze-casting, etching, and 3-D printing) to fabricate scaffolds with different topographic orientations, as well as discussed the physicochemical (mechanical properties, porosity, hydrophilicity, and degradation) and biological properties (morphology, distribution, adhesion, proliferation, and migration) of different topographies. Subsequently, we have compiled the effect of scaffold orientation on the regeneration of vessels, skin, neural tissue, bone, articular cartilage, ligaments, tendons, cardiac tissue, corneas, skeletal muscle, and smooth muscle. The compiled information in this review will facilitate the future development of optimal topographical scaffolds for the regeneration of certain tissues. In the majority of tissues, aligned scaffolds are more suitable than random scaffolds for tissue repair and regeneration. The underlying mechanism explaining the various effects of aligned and random orientation might be the differences in “contact guidance”, which stimulate certain biological responses in cells.

The effect of pore size on cell behavior in mesoporous bioglass scaffolds for bone regeneration

The material properties of bone tissue repair scaffolds dictate the interaction between the material and tissues or cells in vivo. The interface between them at the nanoscale can regulate cell adhesion, migration, and differentiation behaviors, thereby reshaping osteogenic properties of the material in vivo. In this study, a series of 3 nm, 8 nm and 20 nm mesoporous bioactive glass scaffolds (MSX-3, MSX-8 and MSX-20) were prepared by employing sol-gel technique and active self-assembly, with mesoporous bioglass serving as matrix. We then further examined effects of different mesopore pore sizes on the material biology of scaffolds and effects of osteogenic properties both in vitro and in vivo. The prepared multi-level micro-nano-structured bone repair scaffolds all had ∼300 μm macropores and possessed good biocompatibility and in vitro mineralizing activity. In vitro mineralization experiments proved that a large amount of calcium and phosphate salts were deposited on the surfaces of MSX-3 and MSX-8 scaffolds, while MSX-20 had conspicuous adsorption/deposition effects on organic compounds such as proteins in solution. MSX-20 multi-level micro-nano-structured bone repair scaffold could significantly promote the cell adhesion of BMSCs, and the cell spreading area was significantly larger than that of MSX-3 and MSX-8 scaffolds. MSX-20 multi-level micro-nano structured bone repair scaffold had a good sustained release effect on BMP-2, which could promote the osteogenic differentiation effect of BMP-2 on BMSCs. In vivo animal experiments also showed that MSX-20 loaded with BMP-2 could significantly promote in vivo osteogenesis. These findings suggest that when the mesopore pore size is 20 nm, the scaffold can be more conductive to bone regeneration due to the enhanced adhesion of stem cells and more sustained release of BMP-2.

3D Bioprinted Scaffolds for Tissue Repair and Regeneration

Three-dimensional (3D) printing technology has emerged as a revolutionary manufacturing strategy that could realize rapid prototyping and customization. It has revolutionized the manufacturing process in the fields of electronics, energy, bioengineering and sensing. Based on digital model files, powdered metal, plastic and other materials were used to construct the required objects by printing layer by layer. In addition, 3D printing possesses remarkable advantages in realizing controllable compositions and complex structures, which could further produce 3D objects with anisotropic functions. In recent years, 3D bioprinting technology has been applied to manufacture functional tissue engineering scaffolds with its ability to assemble complicated construction under precise control, which has attracted great attention. Bioprinting creates 3D scaffolds by depositing and assembling biological and/or non-biological materials with an established tissue. Compared with traditional technology, it can create a structure tailored to the patient according to the medical images. This conception of 3D bioprinting draws on 3D printing technology, which could be utilized to produce personalized implants, thereby opening up a new way for bio-manufacturing methods. As a promising tool, 3D bioprinting can create complex and delicate biomimetic 3D structures, simulating extracellular matrix and preparing high precision multifunctional scaffolds with uniform cell distribution for tissue repair and regeneration. It can also be flexibly combined with other technologies such as electrospinning and thermally induced phase separation, suitable for tissue repair and regeneration. This article reviews the relevant research and progress of 3D bioprinting in tissue repair and regeneration in recent years. Firstly, we will introduce the physical, chemical and biological characteristics of biological scaffolds prepared by 3D bioprinting from several aspects. Secondly, the significant effects of 3D bioprinting on nerves, skin, blood vessels, bones and cartilage injury and regeneration are further expounded. Finally, some views on the clinical challenges and future opportunities of 3D bioprinting are put forward.

Biomaterial and biocompatibility evaluation of tunicate nanocellulose for tissue engineering.

Extracellular matrix fibril components, such as collagen, are crucial for the structural properties of several tissues and organs. Tunicate-derived cellulose nanofibrils (TNC) combined with living cells could become the next gold standard for cartilage and soft-tissue repair, as TNC fibrils present similar dimensions to collagen, feasible industrial production, and chemically straightforward and cost-efficient extraction procedures. In this study, we characterized the physical properties of TNC derived from aquaculture production in Norwegian fjords and evaluated its biocompatibility regarding induction of an inflammatory response and foreign-body reactions in a Wistar rat model. Additionally, histologic and immunohistochemical analyses were performed for comparison with expanded polytetrafluoroethylene (ePTFE) as a control. The average length of the TNC as determined by atomic force microscopy was tunable from 3μm to 2.4μm via selection of a various number of passages through a microfluidizer, and rheologic analysis showed that the TNC hydrogels were highly shear-thinning and with a viscosity dependent on fibril length and concentration. As a bioink, TNC exhibited excellent rheological and printability properties, with constructs capable of being printed with high resolution and fidelity. We found that post-print cross-linking with alginate stabilized the construct shape and texture, which increased its ease of handling during surgery. Moreover, after 30days in vivo, the constructs showed a highly-preserved shape and fidelity of the grid holes, with these characteristics preserved after 90days and with no signs of necrosis, infection, acute inflammation, invasion of neutrophil granulocytes, or extensive fibrosis. Furthermore, we observed a moderate foreign-body reaction involving macrophages, lymphocytes, and giant cells in both the TNC constructs and PTFE controls, although TNC was considered a non-irritant biomaterial according to ISO 10993-6 as compared with ePTFE. These findings represent a milestone for future clinical application of TNC scaffolds for tissue repair. One sentence summary: In this study, the mechanical properties of tunicate nanocellulose are superior to nanocellulose extracted from other sources, and the biocompatibility is comparable to that of ePTFE.

Characterization of biocompatible scaffolds manufactured by fused filament fabrication of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate).

We characterize poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH) scaffolds for tissue repair and regeneration, manufactured by three-dimensional fused filament fabrication (FFF). PHBH belongs to the class of polyhydroxyalkanoates with interesting biodegradable and biocompatible capabilities, especially attractive for tissue engineering. Equally, FFF stands as a promising manufacturing technology for the production of custom-designed scaffolds. We address thermal, rheological and cytotoxicity properties of PHBH, placing special emphasis on the mechanical response of the printed material in a wide deformation range. Indeed, effective mechanical properties are assessed in both the linear and nonlinear regime. To warrant uniqueness of the material parameters, these are measured directly through digital image correlation, both in tension and compression, while experimental data fitting of finite-element analyses is only adopted for the determination of the second invariant coefficient in the nonlinear regime. Mechanical data are clearly porosity dependent, and they are given for both the cubic and the honeycomb infill pattern. Local strain spikes due to the presence of defects are observed and measured: those falling in the range 70–100% lead to macro-crack development and, ultimately, to failure. Results suggest the significant potential attached to FFF printing of PHBH for customizable medical devices which are biocompatible and mechanically resilient.

Methods to Characterize Granular Hydrogel Rheological Properties, Porosity, and Cell Invasion

Granular hydrogels are formed through the packing of hydrogel microparticles and are emerging for various biomedical applications, including as inks for 3D printing, substrates to study cell-matrix interactions, and injectable scaffolds for tissue repair. Granular hydrogels are suited for these applications because of their unique properties including inherent porosity, shear-thinning and self-healing behavior, and tunable design. The characterization of their material properties and biological response involves technical considerations that are unique to modular systems like granular hydrogels. Here, we describe detailed methods that can be used to quantitatively characterize the rheological behavior and porosity of granular hydrogels using reagents, tools, and equipment that are typically available in biomedical engineering laboratories. In addition, we detail methods for 3D cell invasion assays using multicellular spheroids embedded within granular hydrogels and describe steps to quantify features of cell outgrowth (e.g., endothelial cell sprouting) using standard image processing software. To illustrate these methods, we provide examples where features of granular hydrogels such as the size of hydrogel microparticles and their extent of packing during granular hydrogel formation are modulated. Our intent with this resource is to increase accessibility to granular hydrogel technology and to facilitate the investigation of granular hydrogels for biomedical applications.

Multifunctional Biomedical Materials Derived from Biological Membranes.

The delicate structure and fantastic functions of biological membranes are the successful evolutionary results of a long-term natural selection process. Their excellent biocompatibility and biofunctionality are widely utilized to construct multifunctional biomedical materials mainly by directly camouflaging materials with single or mixed biological membranes, decorating or incorporating materials with membrane-derived vesicles(e.g., exosomes), and designing multifunctional materials with the structure/functions of biological membranes. Here, the structure-function relationship of some important biological membranes and biomimetic membranes are discussed, such as various cell membranes, extracellular vesicles, and membranes from bacteria and organelles. Selected literature examples of multifunctional biomaterials derived from biological membranes for biomedical applications, such as drug- and gene-delivery systems, tissue-repair scaffolds, bioimaging, biosensors, and biological detection, are also highlighted. These designed materials show excellent properties, such as long circulation time, disease-targeted therapy, excellent biocompatibility, and selective recognition. Finally, perspectives and challenges associated with the clinical applications of biological-membrane-derived materials are discussed.

Benefits in the Macrophage Response Due to Graphene Oxide Reduction by Thermal Treatment

Graphene and its derivatives are very promising nanomaterials for biomedical applications and are proving to be very useful for the preparation of scaffolds for tissue repair. The response of immune cells to these graphene-based materials (GBM) appears to be critical in promoting regeneration, thus, the study of this response is essential before they are used to prepare any type of scaffold. Another relevant factor is the variability of the GBM surface chemistry, namely the type and quantity of oxygen functional groups, which may have an important effect on cell behavior. The response of RAW-264.7 macrophages to graphene oxide (GO) and two types of reduced GO, rGO15 and rGO30, obtained after vacuum-assisted thermal treatment of 15 and 30 min, respectively, was evaluated by analyzing the uptake of these nanostructures, the intracellular content of reactive oxygen species, and specific markers of the proinflammatory M1 phenotype, such as CD80 expression and secretion of inflammatory cytokines TNF-α and IL-6. Our results demonstrate that GO reduction resulted in a decrease of both oxidative stress and proinflammatory cytokine secretion, significantly improving its biocompatibility and potential for the preparation of 3D scaffolds able of triggering the appropriate immune response for tissue regeneration.

Prefunctionalised PLGA microparticles with dimethylaminoethyl moieties promote surface cell adhesion at physiological condition

Synthetic hydrolytically degradable polyesters have seen widespread translation into a variety of clinical and biomedical settings; finding use as cell culture systems, drug delivery systems, tissue repair scaffolds, and medical devices. This success is owed in part due to their biocompatible nature and tuneable degradation profile. However, the lack of adhesion moieties limits the capacity of the polyesters to interact with cellular material and as such hampers their effectiveness within these applications. Several physical and chemical post-modification techniques have been developed to insert adhesion moieties; however, the nature of these methods remains complex and troublesome for translational medicine. To combat this flaw, we present a novel prefunctionalization method for the generation of poly (lactic-co-glycolic acid) PLGA microparticles with integrated adhesion moieties as a proof-of-principle. This strategy promotes surface cell adhesion at physiological conditions without the requirement for further post-modification. The basis of the prefunctionalization method was to utilise the 2-2-dimethylaminoethanol as an initiator in a standard bulk Ring Opening Polymerization process to obtain PLGADMAE polymers. The resultant polymers were subsequently used in the fabrication of the microparticles, via membrane emulsion. This process allowed control over the morphology and size distribution of the microparticles. The surface cell adhesive properties of the new PLGADMAE microparticles were investigated via co-culture with Adipose-Derived Stem Cells. Scanning Electron Microscopy showed that the new PLGADMAE microparticles readily promote adhesion of the ADSCs at physiological conditions. LDH and LIVE/DEAD assays demonstrated that the surface functionalised PLGADMAE microparticles maintained a low toxicity profile compared to the unmodified PLGA microparticles. Both thermogravimetric and differential scanning calorimetric analysis confirmed that the bulk properties of the polymer remained unchanged compared to the control PLGA. Gel Permeation Chromatography and Scanning Electron Microscopy imaging showed that the degradation profile of the new PLGADMAE was enhanced compared to that of standard PLGA polymers. This novel prefunctionalization strategy eliminates the need for post-modification and could evolve rapidly to develop biodegradable biomaterials with enhanced cell adhesion and tuneable surface chemistry to allow greater control and/or maintain interaction with living cells and tissues. The implication of this new approach would be far reaching in the field of cell delivery, cell expansion, tissue engineering and regenerative medicine.