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Open AccessPeriodontics

Role of Biomaterial Scaffolds in Periodontal Tissue Engineering-a Prospective Review

  • Dr. Naina PattnaikReader
  • Dr. Monalisa PandaSr. Lecturer
  • Dr. Shubam ThakurIntern

Department of Periodontics Hi-Tech Dental College & Hospital, Bhubaneswar, Odisha

Guident · Volume 14, Issue 3 (February 2021)Published February 202121 min read

ACKNOWLEDGEMENT


We Acknowledged the valuable contribution of Dr. Ankita Rath, Tutor, Department of Conservative Dentistry, Hi-Tech Dental College & Hospital, Bhubaneswar, Odisha, in making this article.

ABSTRACT

Periodontal disease is one of the most common diseases of oral cavity affecting the masses. Conventional therapies of scaling and root planning, GTR, bone grafts were used to restore the lost periodontal tissue. This review article focuses on the application of tissue engineering and scaffold designing in periodontal regeneration and also its development with time. It also talks about the future challenges which need to be addressed by the scientist for the development of innovative biomaterial design.

Key word: Tissue Engineering, Scaffold Material, Periodontal Regeneration

INTRODUCTION

The periodontium of a tooth consists of gingiva periodontal ligament and alveolar bone. Periodontal disease is the inflammation of periodontal tissues that starts due to formation of oral bacterial biofilm that lead to periodontal tissue destruction and ultimately tooth loss. Morbidity of these ranges from 30 to 40% in individuals over 35 years of age making it a global concern.(1)

HISTORICAL PERSPECTIVE

Conventional treatment focused on removal of causative agents which reduced the inflammation but failed to cause regeneration of periodontal tissues.(2)However it was found by clinicians that collapse of gingival tissue in periodontal defects have hampered bone regeneration.(3,4) The concept of GTR (Guided Tissue Regeneration) was introduced by Nyman and colleagues that involves use of synthetic membrane that presented the gingival epithelium and connective tissue to come in the site of healing periodontal wound.(5) Efficacy of this technique is being shown in various clinical studies(6) and systematic reviews.(7)

CHALLENGES FACED

  • Unpredictable outcomes with the very nature of defects and also practitioner's skill and expertise.(8)
  • Oral microbiome exposure in the open only causes poor regeneration in this procedure.(9)
  • Periodontal regeneration is a complex and well-coordinated process. So complete regeneration that is incompetent regeneration of cementum periodontal ligament attachment and formation of bone(4) is achieved unpredictably.(8)

TISSUE ENGINEERING APPLICATIONS IN PERIODONTOLOGY

Historically e several growth factors like PDGF and BMP 2 have proven to be useful in periodontal regeneration. Recently tissue engineering has added a new dimension in the periodontal regeneration.(10) It involves a triad of three things. They are cells, signalling molecules and scaffold matrices.(11) Among these scaffolds act as matrix where attachment migration and proliferation of cells occur in an organised manner in three dimensions.(12)Various natural and synthetic materials are used for the preparation of scaffold. They are:

  • Natural Biomaterials
    1. Collagen: in bone tissue engineering, it serves as an important component of extracellular matrix. Collagen with bioceramic resembles the extracellular matrix of bone in a non-bearing area.(13)
    2. Chitosan: Polysaccharide with antifungal antibacterial analgesic properties and causes Rapid clot formation.(14)
    3. Alginate: Alginate can help in forming scaffold and help in regenerating medicine for bone tissue engineering.(15)
  • Synthetic scaffold materials
    1. Polycaprolactone: It is biocompatible and because of its maintenance while regenerating bone volume causes it slow degeneration and increases mechanical stability.(16)
    2. Polylactic acid, Polyglycolic acid Poly lactic-co-glycolic acid: All are hydrophobic except polyglycolic acid. They have an increased degradation rate in comparison to polycaprolactone.(17)

Other materials that are commonly used are bioceramics. In bioceramics there are calcium phosphate bioceramic, hydroxyapatite, beta tricalcium phosphate and bioactive glass. Also hydrogels are also used which consist of dex. GMA, gelatin gel, collagen gel and gelatinous carrier.

Disadvantages of each biomaterial

  1. Natural biomaterial:
    1. Weak mechanical property.
    2. Fast degradation time due to enzymatic activity. (18-21)
    3. Lack of bioactivity in the regeneration of hard tissue.(22)
  2. Synthetic biomaterial:
    1. During degradation, acidic products are released which cause necrosis of tissues and then scaffold exposure.(23)
  3. Bioceramics:
    1. Difficulty in sleeping due to its low moulting property.(24)Weak mechanical strength(25)and fracture toughness.(26)
  4. Hydrogels:
    1. Low mechanical strength.

THE METHOD BY WHICH SCAFFOLD ARE MOSTLY PREPARED ARE:

  1. Electrospinning. It is a universal technique to manufacture micro to nanofiber and it resembles a natural extracellular matrix.(27) The machine contains a syringe containing the polymer solution or its melt. A pump is present to load the syringe and an electric field exists in between the syringe and the collector plate.(28) Under the electric field difference the polymer gets deposited in the form of micro and nanofibers.(29) These micro and nano fibres have similarity with extracellular matrix and its scaffold favours proliferation, adaptation migration and differentiation of cells.(30)
  2. 3D printing: It uses the data from computed tomography(31) and then fabricates custom made scaffolds which have huge accuracy in details and have specific functions.(32) The materials which are used here are polycarbonate, polycaprolactone, acrylonitrile, butadiene, styrene and poly lactic acid.(33)

Other methods by which preformed scaffolds are fabricated are lyophilization, direct casting.

MONOPHASIC SCAFFOLDS:

Monophasic scaffolds are made following the principles of GTR. Bioactivity in it is incorporated by using biological and events that promote bone and ligament regeneration. Its usage expanded in a wide area in periodontal regeneration. They are used to deliver a wide variety of products which includes:

  • Drugs
    1. Statins: It inhibits osteoclastic activity and increases BMP level and also inhibits HMG CoA level. Its application in monophasic scaffold has led to pocket depth reduction and CAL gain.(34-39)
    2. Metformin: It increases osteogenic differentiation and formation of bone by LKB 1/AMPK pathway. Its application also led to decreased pocket depth and CAL gain.(40-42)
  • Growth factors
    1. Platelet derived growth factor. It increases the chemotaxis and also it enhances angiogenesis which gradually promotes wound healing. It promoted bone regeneration at its best at concentration of 0.3 mg/ml.(43-47)
    2. Fibroblast growth factor: They also promote angiogenesis and wound healing and significantly affect bone regeneration.(48-53)
    3. Bone morphogenetic protein: BMP 2 and BMP 7 are used as growth factors which enhance bone and cartilage formation by activating osteoblast and promote wound healing and angiogenesis.(54-57)

CONTROLLED DELIVERY OF PERIODONTAL REGENERATION:

Controlling the release of the growth factors is a pivotal importance as their half-lives are quite narrow. The drug delivery system can be divided into monodrug delivery system and multi drug delivery system.

In a monodrug delivery system, a single drug or growth factor fulfills a particular function. Bioactive agents can combine with biomaterials by physical entrapment, ionic complexation and surface adsorption.

Natural biomaterials like heparin or heparan sulfate glycosaminoglycan have receptors which can interact with bioactive molecules and protect them from proteolytic degradation. Based on this principle the hierarchical nanosphere-en-capsulated microsphere system was developed for bone regeneration.(58)

The regeneration process is a complicated one and involves factors like inflammation and infection control, stem cell recruitment, promoting differentiation and proliferation of cells. All of them work in a synchronised manner to form the regenerated tissue. So, a multidrug approach is necessary. Also multidrug approach incorporates use of antibiotics to prevent infection several methods of multidrug release are direct presentation, multiphase loading and particulate based delivery.

  • Direct presentation: It involves entrapment of two or more bioactive agents by absorbance procedure.
  • Multiphase loading: Here different bioactive agents entrap in various phase of biomaterials to form a drug carrier which is multiphasic. For example, Lovastatin in PLGA microsphere which is encapsulated in chitosan can be loaded with tetracycline.(59)
  • Particulate based delivery: In this the bioactive agents are incorporated in different particulates and if incorporation occurs into a scaffold.

APPLICATION

  • Periodontal ligament regeneration:

Many periodontal ligament scaffolds are fabricated in nanofibers fibrous mattresses. This scaffold facilitates differentiation of fibroblast and pdl markers expression.(60,61)

Electrospinning method is used to fabricate matrices that are properly oriented.(62) Channel-containing scaffold can also be used to guide the cells and direction of the fibres in three dimension.(63)

Freeze-drying scaffolds were made to direct the fibres in horizontal, apical and oblique groups.(64) But in vivo or in vitro data couldn't show the effectiveness of it.

Similarly 3D printing process was used to produce microstructure which directed the angulation.(65) But no in vivo results confirmed the process. Mechanical stress increased tendon related markers (Periostin and Tenasin)and cause pdl cells to proliferate and differentiate.(66) But the application of mechanical stress in in vivo models to regenerate functional pdl couldn't occur.

CEMENTUM AND ALVEOLAR BONE REGENERATION

Being a hard tissue' inorganic materials like calcium phosphate are used in scaffold for regeneration of bone or cementum. Also natural and synthetic polymers are also used in scaffold to prevent the brittleness and fabrication problem.(67,68)

Alveolar bone regeneration require BMP and amelogenin as growth factors. Cementum regeneration required specific markers like CEMP 1 (Cementum Protein 1) which influence cementum formation and repair. It also promotes hydroxyapatite and mineral tissue formation.(69,70)

New strategies include the use of immunomodulatory strategy to regenerate alveolar bone.(71)Macrophages are segregated phenotypically into:-

  1. Pro inflammatory M1 macrophage
  2. Pro healing M2 macrophage

It is found that the M1 macrophage changes to to M2 macrophage phenotype equally under the presence of cytokine IL-4. So this immunomodulatory finding was incorporated in developing osteo immunomodulatory scaffold.(71) In vivo study revealed that there is switching from the proinflammatory to pro healing macrophage increasing the osteoblastic differentiation and bone regeneration takes place.

Alveolar bone-Periodontal ligament-cementum complex regeneration

The periodontal tissues form a complex entity and one scaffold for each part can be designed tufan a multi tissue regeneration hotstar the scaffold that were developed are:-

  1. Chitin-PLGA-bioglass composite scaffold.
  2. Cell sheet acting as a cementum layer and combining with periodontal ligament and alveolar bone compartment.

However all of them failed in Sharpey's fibre regeneration which is of utmost importance in maintaining the integrity of periodontium scaffolds are able to guide the orientation of periodontal ligament fibres but are not able to guide the orientation of Sharpey's fibres.

MONOPHASIC SCAFFOLD

Sl. No.

Scientists

Scaffold

Results

1.

Dan et al. (2014) (74)

Polycaprolactone+ calcium phosphate coated sheets

Long term stability of scaffold demonstrated in surgerically treated rodent periodontal defect

2.

Cheng et al.(2012) (75)

Poly(D,L-lactide-co-glycolide)+ Poly(D,L-lactide)+ Simvastatin

Applied Simvastatin in core and PDGF in shell which provides better control over release profile and sustained delivery.

3.

Puppi et al (2017) (76)

Medical Grade Polycaprolactone Electrospun fibres +Azithromycin

Enhanced tissue regeneration and protection from bacterial contamination

4.

Chantarawaratit et al. (2014) (77)

Acemannan(Natural polysaccharide extracted from aloe vera)

Enhanced periodontal regeneration with extensive cementum deposition and bone recovery

BIPHASIC SCAFFOLD

Sl. No.

Scientists

Scaffold

Results

1.

Requicha et al. (2014) (78)

PCL/Starch scaffold+ Occlusive membrane of same material

In-vitro utilization shows high potential for osteogenesis

2.

Pedro F Costa et al. (2014) (82)

Fused deposition modelled bone compartment + Melt electrospun periodontal ligament. Bone compartment coated with calcium phosphate layer

In vitro study shows increased alkaline phosphatase activity in Calcium Phosphate coated sample. In vivo study shows more bone formation

3.

C Vaquette et al. (2012) (83)

Fused deposition modelling scaffold ( bone compartment) and a electrospun membrane (periodontal compartment)

In-vitro data showed shows osteoblast formed mineralized matrix in bone compartment and PDL cell sheets didn’t induce cell death

4.

TacGhee Yi et al. (2016)(84)

BMP2-overexpressing human periodontal ligament stem cells(hPDLSC) combined with biphasic calcium phosphate block scaffolds

In vitro transwell assay shows that hPDLSCs exert inhibitory effect on BMP2 induced osteogenic differentiation.

5.

Liren Levin et al. (2020) (85)

Bioresorbable polymer poly(lactide- co-glycolic acid)(PLGA) coated biphasic calcium phosphate(BCP) material

Implant placement with simultaneous bone grafting using in situ hardening BCP shows clinically stable.

TRIPHASIC SCAFFOLD

Sl. No.

Scientists

Scaffold

Results

1.

Varoni et al. (2018) (79)

Chitosan scaffold containing freeze gingival and bone compartment + periodontal compartment

Significant mineralization in bone compartment CEMP1 positive mineralised nodules in dentin interface and soft tissue intercalation between the mineralised tissue

2.

G Criscenti et al. (2016)(86)

3D fiber deposited polycaprolactone structure and a polylactic co-glycolic acid electrospun

Higher activity of alkaline phosphate activity in triphasic scaffold in mineralization medium

3.

S A Catledge et al. (2007) (87)

Mixture of polycaprolactone, type I collagen and hydroxyapatite nanoparticles in dry weight ratio of 50:30:20

Hydrocyapetite particles were uniformly dispersed. The modulus data showed the importance of collagen and its interaction with other components in improving mechanical properties of osteoconductive scaffold.

4.

Lee et al. (2014) (88)

Multiphase region specific microscaffolds with spatiotemporal delivery of bioactive cues

4 weeks in vitro incubation separately with dental pulp stem cells(DPSCs), PDL stem cells(PDLSCs) or alveolar bone stem cells(ABSCs), distinctive tissue phenotypes were formed with collagen I rich fibers by PDLSCs and mineralized tissue by DPSCs, PDLSCs and ABSCs.

CELL SHEETS AND SCAFFOLD FREE CONSTRUCT

Sl. No.

Scientists

Scaffold

Results

1.

Okano et al. (2011,2005) (80,81)

PDL cell sheets ectopically implanted to dentin slices

Mature extracellular matrix network was attended

FUTURE CHALLENGES

Although scaffold designing has undergone numerous development in the recent past but still it is unable to completely regenerate the periodontium. Some of the limitations that we need to overcome for further progress in periodontal regeneration are:

  • With advancement tissue engineering was able to develop cellular cementum but not acellular cementum.(72)
  • Although the bio materials resemble the composition in various aspects they can't mimic fine details of natural periodontium.
  • More controlled delivery of bio physical and chemical cues are required for proper synchronised regeneration of periodontal tissues.
  • Multidrug Delivery System still fails to achieve the controlled release for periodontal regeneration.(73)
  • Although the scientists have addressed the problem of vertical bone loss but still very few studies are being done to restore horizontal bone loss.(73)

CONCLUSION

In spite of all these challenges periodontal regeneration appears to be a promising and rapidly developing field. These advances hold a huge potential to restore and improve the periodontal as well as the overall health of every patient in the near future.

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How to cite this article

Dr. Naina Pattnaik, Dr. Monalisa Panda, Dr. Shubam Thakur. Role of Biomaterial Scaffolds in Periodontal Tissue Engineering-a Prospective Review. Guident. 2021 Feb;14(3). Available from: https://guident.in/articles/periodontics/role-of-biomaterial-scaffolds-in-periodontal-tissue-engineering-a-prospective-review.html

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